Pituitary crosstalk with bone, adipose tissue and brain.
Journal
Nature reviews. Endocrinology
ISSN: 1759-5037
Titre abrégé: Nat Rev Endocrinol
Pays: England
ID NLM: 101500078
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
accepted:
18
08
2023
medline:
13
11
2023
pubmed:
16
9
2023
entrez:
15
9
2023
Statut:
ppublish
Résumé
Traditional textbook physiology has ascribed unitary functions to hormones from the anterior and posterior pituitary gland, mainly in the regulation of effector hormone secretion from endocrine organs. However, the evolutionary biology of pituitary hormones and their receptors provides evidence for a broad range of functions in vertebrate physiology. Over the past decade, we and others have discovered that thyroid-stimulating hormone, follicle-stimulating hormone, adrenocorticotropic hormone, prolactin, oxytocin and arginine vasopressin act directly on somatic organs, including bone, adipose tissue and liver. New evidence also indicates that pituitary hormone receptors are expressed in brain regions, nuclei and subnuclei. These studies have prompted us to attribute the pathophysiology of certain human diseases, including osteoporosis, obesity and neurodegeneration, at least in part, to changes in pituitary hormone levels. This new information has identified actionable therapeutic targets for drug discovery.
Identifiants
pubmed: 37715028
doi: 10.1038/s41574-023-00894-5
pii: 10.1038/s41574-023-00894-5
doi:
Substances chimiques
Pituitary Hormones
0
Prolactin
9002-62-4
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
708-721Informations de copyright
© 2023. Springer Nature Limited.
Références
Rosen, E. D. & Carter-Su, C. in Williams Textbook of Endocrinology (eds Melmed, S. et al.) Ch. 2, 13–41 (Elsevier, 2020).
Abe, E. et al. TSH is a negative regulator of skeletal remodeling. Cell 115, 151–162 (2003).
doi: 10.1016/S0092-8674(03)00771-2
pubmed: 14567913
Sun, L. et al. FSH directly regulates bone mass. Cell 125, 247–260 (2006).
doi: 10.1016/j.cell.2006.01.051
pubmed: 16630814
Liu, P. et al. Blocking FSH induces thermogenic adipose tissue and reduces body fat. Nature 546, 107–112 (2017).
doi: 10.1038/nature22342
pubmed: 28538730
pmcid: 5651981
Xiong, J. et al. FSH blockade improves cognition in mice with Alzheimer’s disease. Nature 603, 470–476 (2022).
doi: 10.1038/s41586-022-04463-0
pubmed: 35236988
pmcid: 9940301
Gera, S. et al. FSH-blocking therapeutic for osteoporosis. eLife 11, e78022 (2022).
Gera, S. et al. First-in-class humanized FSH blocking antibody targets bone and fat. Proc. Natl Acad. Sci. USA 117, 28971–28979 (2020).
doi: 10.1073/pnas.2014588117
pubmed: 33127753
pmcid: 7682550
Yamashita, K. & Kitano, T. Molecular evolution of the oxytocin–oxytocin receptor system in eutherians. Mol. Phylogenet. Evol. 67, 520–528 (2013).
doi: 10.1016/j.ympev.2013.02.017
pubmed: 23485918
Knobloch, H. S. & Grinevich, V. Evolution of oxytocin pathways in the brain of vertebrates. Front. Behav. Neurosci. 8, 31 (2014).
doi: 10.3389/fnbeh.2014.00031
pubmed: 24592219
pmcid: 3924577
Garrison, J. L. et al. Oxytocin/vasopressin-related peptides have an ancient role in reproductive behavior. Science 338, 540–543 (2012).
doi: 10.1126/science.1226201
pubmed: 23112335
pmcid: 3597094
Gimpl, G. & Fahrenholz, F. The oxytocin receptor system: structure, function, and regulation. Physiol. Rev. 81, 629–683 (2001).
doi: 10.1152/physrev.2001.81.2.629
pubmed: 11274341
Kleinau, G. & Krause, G. Thyrotropin and homologous glycoprotein hormone receptors: structural and functional aspects of extracellular signaling mechanisms. Endocr. Rev. 30, 133–151 (2009).
doi: 10.1210/er.2008-0044
pubmed: 19176466
Davies, T., Marians, R. & Latif, R. The TSH receptor reveals itself. J. Clin. Invest. 110, 161–164 (2002).
doi: 10.1172/JCI0216234
pubmed: 12122107
pmcid: 151075
Bogerd, J., Granneman, J. C., Schulz, R. W. & Vischer, H. F. Fish FSH receptors bind LH: how to make the human FSH receptor to be more fishy? Gen. Comp. Endocrinol. 142, 34–43 (2005).
doi: 10.1016/j.ygcen.2004.12.008
pubmed: 15862546
Kobayashi, T. & Andersen, O. The gonadotropin receptors FSH-R and LH-R of Atlantic halibut (Hippoglossus hippoglossus), 1: isolation of multiple transcripts encoding full-length and truncated variants of FSH-R. Gen. Comp. Endocrinol. 156, 584–594 (2008).
doi: 10.1016/j.ygcen.2008.02.008
pubmed: 18359484
Cooray, S. N. & Clark, A. J. Melanocortin receptors and their accessory proteins. Mol. Cell Endocrinol. 331, 215–221 (2011).
doi: 10.1016/j.mce.2010.07.015
pubmed: 20654690
Wilson, M. G. et al. Proopiolipomelanocortin peptides in normal pituitary, pituitary tumor, and plasma of normal and Cushing’s horses. Endocrinology 110, 941–954 (1982).
doi: 10.1210/endo-110-3-941
pubmed: 6276164
Baudet, M. L., Sanders, E. J. & Harvey, S. Retinal growth hormone in the chick embryo. Endocrinology 144, 5459–5468 (2003).
doi: 10.1210/en.2003-0651
pubmed: 12960021
Harvey, S., Kakebeeke, M. & Sanders, E. J. Growth hormone localization in the neural retina and retinal pigmented epithelium of embryonic chicks. J. Mol. Neurosci. 22, 139–145 (2004).
doi: 10.1385/JMN:22:1-2:139
pubmed: 14742918
Martinez-Moreno, C. G. et al. Growth hormone protects against kainate excitotoxicity and induces BDNF and NT3 expression in chicken neuroretinal cells. Exp. Eye Res. 166, 1–12 (2018).
doi: 10.1016/j.exer.2017.10.005
pubmed: 29030174
Harvey, S. & Aramburo, C. Growth hormone: not just a pituitary endocrine. J. Endocr. Disord. 4, 1024 (2017).
Martin, B. T., List, E. O., Kopchick, J. J., Sauve, Y. & Harvey, S. Selective inner retinal dysfunction in growth hormone transgenic mice. Growth Horm. IGF Res. 21, 219–227 (2011).
doi: 10.1016/j.ghir.2011.05.008
pubmed: 21705251
pmcid: 4151295
Grimbly, C., Martin, B., Karpinski, E. & Harvey, S. Growth hormone production and action in N1E-115 neuroblastoma cells. J. Mol. Neurosci. 39, 117–124 (2009).
doi: 10.1007/s12031-009-9194-7
pubmed: 19301152
de Mello-Coelho, V. et al. Growth hormone and its receptor are expressed in human thymic cells. Endocrinology 139, 3837–3842 (1998).
doi: 10.1210/endo.139.9.6199
pubmed: 9724037
Hull, K. L. & Harvey, S. Growth hormone and reproduction: a review of endocrine and autocrine/paracrine interactions. Int. J. Endocrinol. 2014, 234014 (2014).
doi: 10.1155/2014/234014
pubmed: 25580121
pmcid: 4279787
Schwarzler, P. et al. Selective growth hormone/placental lactogen gene transcription and hormone production in pre- and postmenopausal human ovaries. J. Clin. Endocrinol. Metab. 82, 3337–3341 (1997).
pubmed: 9329365
Hull, K. L. & Harvey, S. Growth hormone: roles in male reproduction. Endocrine 13, 243–250 (2000).
doi: 10.1385/ENDO:13:3:243
pubmed: 11216634
Baliram, R. et al. Thyroid and bone: macrophage-derived TSH-beta splice variant increases murine osteoblastogenesis. Endocrinology 154, 4919–4926 (2013).
doi: 10.1210/en.2012-2234
pubmed: 24140716
pmcid: 3836071
Baliram, R., Latif, R., Morshed, S. A., Zaidi, M. & Davies, T. F. T3 regulates a human macrophage-derived TSH-beta splice variant: implications for human bone biology. Endocrinology 157, 3658–3667 (2016).
doi: 10.1210/en.2015-1974
pubmed: 27300765
pmcid: 5007892
Vincent, B. H. et al. Bone marrow cells produce a novel TSHbeta splice variant that is upregulated in the thyroid following systemic virus infection. Genes Immun. 10, 18–26 (2009).
doi: 10.1038/gene.2008.69
pubmed: 18754015
Smith, E. M., Phan, M., Kruger, T. E., Coppenhaver, D. H. & Blalock, J. E. Human lymphocyte production of immunoreactive thyrotropin. Proc. Natl Acad. Sci. USA 80, 6010–6013 (1983).
doi: 10.1073/pnas.80.19.6010
pubmed: 6351072
pmcid: 534349
Harbour, D. V., Kruger, T. E., Coppenhaver, D., Smith, E. M. & Meyer, W. J. 3rd Differential expression and regulation of thyrotropin (TSH) in T cell lines. Mol. Cell. Endocrinol. 64, 229–241 (1989).
doi: 10.1016/0303-7207(89)90150-0
pubmed: 2507375
Klein, J. R. & Wang, H. C. Characterization of a novel set of resident intrathyroidal bone marrow-derived hematopoietic cells: potential for immune–endocrine interactions in thyroid homeostasis. J. Exp. Biol. 207, 55–65 (2004).
doi: 10.1242/jeb.00710
pubmed: 14638833
Colaianni, G. et al. Regulated production of the pituitary hormone oxytocin from murine and human osteoblasts. Biochem. Biophys. Res. Commun. 411, 512–515 (2011).
doi: 10.1016/j.bbrc.2011.06.158
pubmed: 21741363
Colaianni, G. et al. Bone marrow oxytocin mediates the anabolic action of estrogen on the skeleton. J. Biol. Chem. 287, 29159–29167 (2012).
doi: 10.1074/jbc.M112.365049
pubmed: 22761429
pmcid: 3436530
Yakar, S. et al. Circulating levels of IGF-1 directly regulate bone growth and density. J. Clin. Invest. 110, 771–781 (2002).
doi: 10.1172/JCI0215463
pubmed: 12235108
pmcid: 151128
De Jesus, K., Wang, X. & Liu, J. L. A general IGF-I overexpression effectively rescued somatic growth and bone deficiency in mice caused by growth hormone receptor knockout. Growth Factors 27, 438–447 (2009).
doi: 10.3109/08977190903299270
pubmed: 19824875
Bachrach, L. K. et al. Bone mineral, histomorphometry, and body composition in adults with growth hormone receptor deficiency. J. Bone Min. Res. 13, 415–421 (1998).
doi: 10.1359/jbmr.1998.13.3.415
Fritton, J. C. et al. Growth hormone protects against ovariectomy-induced bone loss in states of low circulating insulin-like growth factor (IGF-1). J. Bone Min. Res. 25, 235–246 (2010).
doi: 10.1359/jbmr.090723
Sun, L. et al. Intermittent recombinant TSH injections prevent ovariectomy-induced bone loss. Proc. Natl Acad. Sci. USA 105, 4289–4294 (2008).
doi: 10.1073/pnas.0712395105
pubmed: 18332426
pmcid: 2393772
Baliram, R. et al. Hyperthyroid-associated osteoporosis is exacerbated by the loss of TSH signaling. J. Clin. Invest. 122, 3737–3741 (2012).
doi: 10.1172/JCI63948
pubmed: 22996689
pmcid: 3461920
Kim, S. M. et al. Thyrotropin, hyperthyroidism, and bone mass. J. Clin. Endocrinol. Metab. 106, e4809–e4821 (2021).
pubmed: 34318885
pmcid: 8864741
Novack, D. V. TSH, the bone suppressing hormone. Cell 115, 129–130 (2003).
doi: 10.1016/S0092-8674(03)00812-2
pubmed: 14567908
Hase, H. et al. TNFalpha mediates the skeletal effects of thyroid-stimulating hormone. Proc. Natl Acad. Sci. USA 103, 12849–12854 (2006).
doi: 10.1073/pnas.0600427103
pubmed: 16908863
pmcid: 1568936
Ma, R., Morshed, S., Latif, R., Zaidi, M. & Davies, T. F. The influence of thyroid-stimulating hormone and thyroid-stimulating hormone receptor antibodies on osteoclastogenesis. Thyroid 21, 897–906 (2011).
doi: 10.1089/thy.2010.0457
pubmed: 21745106
pmcid: 3148120
Yamoah, K. et al. High-mobility group box proteins modulate tumor necrosis factor-alpha expression in osteoclastogenesis via a novel deoxyribonucleic acid sequence. Mol. Endocrinol. 22, 1141–1153 (2008).
doi: 10.1210/me.2007-0460
pubmed: 18218727
pmcid: 2366181
Sun, L. et al. Genetic confirmation for a central role for TNFalpha in the direct action of thyroid stimulating hormone on the skeleton. Proc. Natl Acad. Sci. USA 110, 9891–9896 (2013).
doi: 10.1073/pnas.1308336110
pubmed: 23716650
pmcid: 3683712
Baliram, R. et al. Thyroid-stimulating hormone induces a Wnt-dependent, feed-forward loop for osteoblastogenesis in embryonic stem cell cultures. Proc. Natl Acad. Sci. USA 108, 16277–16282 (2011).
doi: 10.1073/pnas.1110286108
pubmed: 21911383
pmcid: 3182731
Sampath, T. K. et al. Thyroid-stimulating hormone restores bone volume, microarchitecture, and strength in aged ovariectomized rats. J. Bone Min. Res. 22, 849–859 (2007).
doi: 10.1359/jbmr.070302
Mazziotti, G. et al. Recombinant human TSH modulates in vivo C-telopeptides of type-1 collagen and bone alkaline phosphatase, but not osteoprotegerin production in postmenopausal women monitored for differentiated thyroid carcinoma. J. Bone Min. Res. 20, 480–486 (2005).
doi: 10.1359/JBMR.041126
Karga, H. et al. The effects of recombinant human TSH on bone turnover in patients after thyroidectomy. J. Bone Min. Metab. 28, 35–41 (2010).
doi: 10.1007/s00774-009-0098-y
Martini, G. et al. The effects of recombinant TSH on bone turnover markers and serum osteoprotegerin and RANKL levels. Thyroid 18, 455–460 (2008).
doi: 10.1089/thy.2007.0166
pubmed: 18399769
Cho, S. W. et al. The presence of thyroid-stimulation blocking antibody prevents high bone turnover in untreated premenopausal patients with Graves’ disease. PLoS ONE 10, e0144599 (2015).
doi: 10.1371/journal.pone.0144599
pubmed: 26650844
pmcid: 4674124
von Recklinghausen, F. in Festschrift für Rudolf Virchow (ed. Reimer, G.) (Druck und Verlag von Georg Reimer, 1891).
Blum, M. R. et al. Subclinical thyroid dysfunction and fracture risk: a meta-analysis. JAMA 313, 2055–2065 (2015).
doi: 10.1001/jama.2015.5161
pubmed: 26010634
pmcid: 4729304
Flynn, R. W. et al. Serum thyroid-stimulating hormone concentration and morbidity from cardiovascular disease and fractures in patients on long-term thyroxine therapy. J. Clin. Endocrinol. Metab. 95, 186–193 (2010).
doi: 10.1210/jc.2009-1625
pubmed: 19906785
Kim, M. K. et al. The effects of thyrotropin-suppressing therapy on bone metabolism in patients with well-differentiated thyroid carcinoma. Bone 71, 101–105 (2015).
doi: 10.1016/j.bone.2014.10.009
pubmed: 25445448
La Vignera, S. et al. L-thyroxin treatment and post-menopausal osteoporosis: relevance of the risk profile present in clinical history. Minerva Ginecol. 60, 475–484 (2008).
pubmed: 18981975
Svare, A. et al. Hyperthyroid levels of TSH correlate with low bone mineral density: the HUNT 2 study. Eur. J. Endocrinol. 161, 779–786 (2009).
doi: 10.1530/EJE-09-0139
pubmed: 19671706
Bauer, D. C., Ettinger, B., Nevitt, M. C. & Stone, K. L., Study of Osteoporotic Fractures Research Group. Risk for fracture in women with low serum levels of thyroid-stimulating hormone. Ann. Intern. Med. 134, 561–568 (2001).
doi: 10.7326/0003-4819-134-7-200104030-00009
pubmed: 12803168
Wang, L. Y. et al. Thyrotropin suppression increases the risk of osteoporosis without decreasing recurrence in ATA low- and intermediate-risk patients with differentiated thyroid carcinoma. Thyroid 25, 300–307 (2015).
doi: 10.1089/thy.2014.0287
pubmed: 25386760
pmcid: 6916125
Karimifar, M. et al. Effects of levothyroxine and thyroid stimulating hormone on bone loss in patients with primary hypothyroidism. J. Res. Pharm. Pract. 3, 83–87 (2014).
doi: 10.4103/2279-042X.141099
pubmed: 25328897
pmcid: 4199196
Abrahamsen, B. et al. The excess risk of major osteoporotic fractures in hypothyroidism is driven by cumulative hyperthyroid as opposed to hypothyroid time: an observational register-based time-resolved cohort analysis. J. Bone Min. Res. 30, 898–905 (2015).
doi: 10.1002/jbmr.2416
Abrahamsen, B. et al. Low serum thyrotropin level and duration of suppression as a predictor of major osteoporotic fractures — the OPENTHYRO register cohort. J. Bone Min. Res. 29, 2040–2050 (2014).
doi: 10.1002/jbmr.2244
Grimnes, G., Emaus, N., Joakimsen, R. M., Figenschau, Y. & Jorde, R. The relationship between serum TSH and bone mineral density in men and postmenopausal women: the Tromso study. Thyroid 18, 1147–1155 (2008).
doi: 10.1089/thy.2008.0158
pubmed: 18925834
Morris, M. S. The association between serum thyroid-stimulating hormone in its reference range and bone status in postmenopausal American women. Bone 40, 1128–1134 (2007).
doi: 10.1016/j.bone.2006.12.001
pubmed: 17236836
Lee, S. J. et al. Low normal TSH levels are associated with impaired BMD and hip geometry in the elderly. Aging Dis. 7, 734–743 (2016).
doi: 10.14336/AD.2016.0325
pubmed: 28053824
pmcid: 5198865
Ding, B. et al. Low thyroid stimulating hormone levels are associated with low bone mineral density in femoral neck in elderly women. Arch. Med. Res. 47, 310–314 (2016).
doi: 10.1016/j.arcmed.2016.07.009
pubmed: 27664492
Waring, A. C. et al. A prospective study of thyroid function, bone loss, and fractures in older men: the MrOS study. J. Bone Min. Res. 28, 472–479 (2013).
doi: 10.1002/jbmr.1774
Acar, B. et al. Evaluation of thyroid function status among postmenopausal women with and without osteoporosis. Int. J. Gynaecol. Obstet. 134, 53–57 (2016).
doi: 10.1016/j.ijgo.2015.11.025
pubmed: 27177516
Noh, H. M., Park, Y. S., Lee, J. & Lee, W. A cross-sectional study to examine the correlation between serum TSH levels and the osteoporosis of the lumbar spine in healthy women with normal thyroid function. Osteoporos. Int. 26, 997–1003 (2015).
doi: 10.1007/s00198-014-2906-z
pubmed: 25253541
van der Deure, W. M. et al. Effects of serum TSH and FT4 levels and the TSHR-Asp727Glu polymorphism on bone: the Rotterdam study. Clin. Endocrinol. 68, 175–181 (2008).
doi: 10.1111/j.1365-2265.2007.03016.x
Albagha, O. M. E., Natarajan, R., Reid, D. M. & Ralston, S. H. The D727E polymorphism of the human thyroid stimulating hormone receptor is associated with bone mineral density and bone loss in women from the UK. J. Bone Min. Res. 20, S341 (2005).
Liu, R. D. et al. The Glu727 allele of thyroid stimulating hormone receptor gene is associated with osteoporosis. N. Am. J. Med. Sci. 4, 300–304 (2012).
doi: 10.4103/1947-2714.98588
pubmed: 22866266
pmcid: 3409653
van Vliet, N. A. et al. Thyroid stimulating hormone and bone mineral density: evidence from a two-sample Mendelian randomization study and a candidate gene association study. J. Bone Min. Res. 33, 1318–1325 (2018).
doi: 10.1002/jbmr.3426
Liu, S., Cheng, Y., Fan, M., Chen, D. & Bian, Z. FSH aggravates periodontitis-related bone loss in ovariectomized rats. J. Dent. Res. 89, 366–371 (2010).
doi: 10.1177/0022034509358822
pubmed: 20139335
Liu, S., Cheng, Y., Xu, W. & Bian, Z. Protective effects of follicle-stimulating hormone inhibitor on alveolar bone loss resulting from experimental periapical lesions in ovariectomized rats. J. Endod. 36, 658–663 (2010).
doi: 10.1016/j.joen.2010.01.011
pubmed: 20307740
Robinson, L. J. et al. FSH-receptor isoforms and FSH-dependent gene transcription in human monocytes and osteoclasts. Biochem. Biophys. Res. Commun. 394, 12–17 (2010).
doi: 10.1016/j.bbrc.2010.02.112
pubmed: 20171950
pmcid: 2856932
Sun, L. et al. Further evidence for direct pro-resorptive actions of FSH. Biochem. Biophys. Res. Commun. 394, 6–11 (2010).
doi: 10.1016/j.bbrc.2010.02.113
pubmed: 20171951
pmcid: 3144627
Wu, Y. et al. Bone microenvironment specific roles of ITAM adapter signaling during bone remodeling induced by acute estrogen-deficiency. PLoS ONE 2, e586 (2007).
doi: 10.1371/journal.pone.0000586
pubmed: 17611621
pmcid: 1895921
Wang, J. et al. Follicle-stimulating hormone increases the risk of postmenopausal osteoporosis by stimulating osteoclast differentiation. PLoS ONE 10, e0134986 (2015).
doi: 10.1371/journal.pone.0134986
pubmed: 26241313
pmcid: 4524683
Allan, C. M. et al. Follicle-stimulating hormone increases bone mass in female mice. Proc. Natl Acad. Sci. USA 107, 22629–22634 (2010).
doi: 10.1073/pnas.1012141108
pubmed: 21149714
pmcid: 3012495
Ritter, V. et al. Follicle-stimulating hormone does not impact male bone mass in vivo or human male osteoclasts in vitro. Calcif. Tissue Int. 82, 383–391 (2008).
doi: 10.1007/s00223-008-9134-5
pubmed: 18465073
Feng, Y. et al. Live imaging of follicle stimulating hormone receptors in gonads and bones using near infrared II fluorophore. Chem. Sci. 8, 3703–3711 (2017).
doi: 10.1039/C6SC04897H
pubmed: 28626555
pmcid: 5465568
Ji, Y. et al. Epitope-specific monoclonal antibodies to FSHbeta increase bone mass. Proc. Natl Acad. Sci. USA 115, 2192–2197 (2018).
doi: 10.1073/pnas.1718144115
pubmed: 29440419
pmcid: 5834707
Meher, B. R., Dixit, A., Bousfield, G. R. & Lushington, G. H. Glycosylation effects on FSH–FSHR interaction dynamics: a case study of different FSH glycoforms by molecular dynamics simulations. PLoS ONE 10, e0137897 (2015).
doi: 10.1371/journal.pone.0137897
pubmed: 26402790
pmcid: 4581761
Cannon, J. G., Kraj, B. & Sloan, G. Follicle-stimulating hormone promotes RANK expression on human monocytes. Cytokine 53, 141–144 (2011).
doi: 10.1016/j.cyto.2010.11.011
pubmed: 21159522
Iqbal, J., Sun, L., Kumar, T. R., Blair, H. C. & Zaidi, M. Follicle-stimulating hormone stimulates TNF production from immune cells to enhance osteoblast and osteoclast formation. Proc. Natl Acad. Sci. USA 103, 14925–14930 (2006).
doi: 10.1073/pnas.0606805103
pubmed: 17003115
pmcid: 1595452
Cannon, J. G. et al. Follicle-stimulating hormone, interleukin-1, and bone density in adult women. Am. J. Physiol. Regul. Integr. Comp. Physiol. 298, R790–R798 (2010).
doi: 10.1152/ajpregu.00728.2009
pubmed: 20042686
Gertz, E. R. et al. Contribution of serum inflammatory markers to changes in bone mineral content and density in postmenopausal women: a 1-year investigation. J. Clin. Densitom. 13, 277–282 (2010).
doi: 10.1016/j.jocd.2010.04.003
pubmed: 20605499
pmcid: 2912969
Zhu, L. L. et al. Blocking antibody to the beta-subunit of FSH prevents bone loss by inhibiting bone resorption and stimulating bone synthesis. Proc. Natl Acad. Sci. USA 109, 14574–14579 (2012).
doi: 10.1073/pnas.1212806109
pubmed: 22908268
pmcid: 3437842
Gao, J. et al. Altered ovarian function affects skeletal homeostasis independent of the action of follicle-stimulating hormone. Endocrinology 148, 2613–2621 (2007).
doi: 10.1210/en.2006-1404
pubmed: 17332067
Danilovich, N. et al. Estrogen deficiency, obesity, and skeletal abnormalities in follicle-stimulating hormone receptor knockout (FORKO) female mice. Endocrinology 141, 4295–4308 (2000).
doi: 10.1210/endo.141.11.7765
pubmed: 11089565
Abel, M. H., Huhtaniemi, I., Pakarinen, P., Kumar, T. R. & Charlton, H. M. Age-related uterine and ovarian hypertrophy in FSH receptor knockout and FSHbeta subunit knockout mice. Reproduction 125, 165–173 (2003).
doi: 10.1530/rep.0.1250165
pubmed: 12578530
Oz, O. K. et al. Bone has a sexually dimorphic response to aromatase deficiency. J. Bone Min. Res. 15, 507–514 (2000).
doi: 10.1359/jbmr.2000.15.3.507
Couse, J. F., Yates, M. M., Walker, V. R. & Korach, K. S. Characterization of the hypothalamic-pituitary-gonadal axis in estrogen receptor (ER) null mice reveals hypergonadism and endocrine sex reversal in females lacking ERalpha but not ERbeta. Mol. Endocrinol. 17, 1039–1053 (2003).
doi: 10.1210/me.2002-0398
pubmed: 12624116
Sims, N. A. et al. Deletion of estrogen receptors reveals a regulatory role for estrogen receptors-beta in bone remodeling in females but not in males. Bone 30, 18–25 (2002).
doi: 10.1016/S8756-3282(01)00643-3
pubmed: 11792560
Khalid, A. B. & Krum, S. A. Estrogen receptors alpha and beta in bone. Bone 87, 130–135 (2016).
doi: 10.1016/j.bone.2016.03.016
pubmed: 27072516
pmcid: 5336249
Devleta, B., Adem, B. & Senada, S. Hypergonadotropic amenorrhea and bone density: new approach to an old problem. J. Bone Min. Metab. 22, 360–364 (2004).
doi: 10.1007/s00774-004-0495-1
Kawai, H., Furuhashi, M. & Suganuma, N. Serum follicle-stimulating hormone level is a predictor of bone mineral density in patients with hormone replacement therapy. Arch. Gynecol. Obstet. 269, 192–195 (2004).
doi: 10.1007/s00404-003-0532-7
pubmed: 13680264
Podfigurna-Stopa, A. et al. Skeletal status and body composition in young women with functional hypothalamic amenorrhea. Gynecol. Endocrinol. 28, 299–304 (2012).
doi: 10.3109/09513590.2011.613972
pubmed: 21957879
Drake, M. T., McCready, L. K., Hoey, K. A., Atkinson, E. J. & Khosla, S. Effects of suppression of follicle-stimulating hormone secretion on bone resorption markers in postmenopausal women. J. Clin. Endocrinol. Metab. 95, 5063–5068 (2010).
doi: 10.1210/jc.2010-1103
pubmed: 20610587
pmcid: 2968737
Rendina, D. et al. FSHR gene polymorphisms influence bone mineral density and bone turnover in postmenopausal women. Eur. J. Endocrinol. 163, 165–172 (2010).
doi: 10.1530/EJE-10-0043
pubmed: 20335500
Mendoza, N. et al. Estrogen-related genes and postmenopausal osteoporosis risk. Climacteric 15, 587–593 (2012).
doi: 10.3109/13697137.2012.656160
pubmed: 22335445
Randolph, J. F. Jr. et al. Reproductive hormones in the early menopausal transition: relationship to ethnicity, body size, and menopausal status. J. Clin. Endocrinol. Metab. 88, 1516–1522 (2003).
doi: 10.1210/jc.2002-020777
pubmed: 12679432
Sowers, M. R. et al. Endogenous hormones and bone turnover markers in pre- and perimenopausal women: SWAN. Osteoporos. Int. 14, 191–197 (2003).
doi: 10.1007/s00198-002-1329-4
pubmed: 12730778
Sowers, M. R. et al. Hormone predictors of bone mineral density changes during the menopausal transition. J. Clin. Endocrinol. Metab. 91, 1261–1267 (2006).
doi: 10.1210/jc.2005-1836
pubmed: 16403818
Greendale, G. A. et al. Bone mineral density loss in relation to the final menstrual period in a multiethnic cohort: results from the Study of Women’s Health Across the Nation (SWAN). J. Bone Min. Res. 27, 111–118 (2012).
doi: 10.1002/jbmr.534
Sowers, M. et al. Performance-based physical functioning in African-American and Caucasian women at midlife: considering body composition, quadriceps strength, and knee osteoarthritis. Am. J. Epidemiol. 163, 950–958 (2006).
doi: 10.1093/aje/kwj109
pubmed: 16554351
Greendale, G. A. et al. Changes in body composition and weight during the menopause transition. JCI Insight 4, e124865 (2019).
doi: 10.1172/jci.insight.124865
pubmed: 30843880
pmcid: 6483504
Greendale, G. A. et al. Effects of the menopause transition and hormone use on cognitive performance in midlife women. Neurology 72, 1850–1857 (2009).
doi: 10.1212/WNL.0b013e3181a71193
pubmed: 19470968
pmcid: 2690984
Lukefahr, A. L. et al. Decreased bone mineral density in rats rendered follicle-deplete by an ovotoxic chemical correlates with changes in follicle-stimulating hormone and inhibin A. Calcif. Tissue Int. 90, 239–249 (2012).
doi: 10.1007/s00223-011-9565-2
pubmed: 22249524
pmcid: 3288225
Xu, Z. R. et al. Relationship of age-related concentrations of serum FSH and LH with bone mineral density, prevalence of osteoporosis in native Chinese women. Clin. Chim. Acta 400, 8–13 (2009).
doi: 10.1016/j.cca.2008.09.027
pubmed: 18930719
Wu, X. Y. et al. Age-related changes in biochemical markers of bone turnover and gonadotropin levels and their relationship among Chinese adult women. Osteoporos. Int. 21, 275–285 (2010).
doi: 10.1007/s00198-009-0943-9
pubmed: 19562242
Cheung, E. et al. Bone loss during menopausal transition among southern Chinese women. Maturitas 69, 50–56 (2011).
doi: 10.1016/j.maturitas.2011.01.010
pubmed: 21310558
Wang, B. et al. Correlation analysis for follicle-stimulating hormone and C-terminal cross-linked telopetides of type I collagen in menopausal transition women with osteoporosis. Int. J. Clin. Exp. Med. 8, 2417–2422 (2015).
pubmed: 25932182
pmcid: 4402829
Gallagher, C. M., Moonga, B. S. & Kovach, J. S. Cadmium, follicle-stimulating hormone, and effects on bone in women age 42–60 years, NHANES III. Environ. Res. 110, 105–111 (2010).
doi: 10.1016/j.envres.2009.09.012
pubmed: 19875111
Adami, S. et al. Determinants of bone turnover markers in healthy premenopausal women. Calcif. Tissue Int. 82, 341–347 (2008).
doi: 10.1007/s00223-008-9126-5
pubmed: 18470550
Veldhuis-Vlug, A. G. et al. Serum FSH is associated with BMD, bone marrow adiposity, and body composition in the AGES-Reykjavik Study of older adults. J. Clin. Endocrinol. Metab. 106, e1156–e1169 (2021).
doi: 10.1210/clinem/dgaa922
pubmed: 33326040
Crandall, C. J. et al. Serum sex steroid levels and longitudinal changes in bone density in relation to the final menstrual period. J. Clin. Endocrinol. Metab. 98, E654–E663 (2013).
doi: 10.1210/jc.2012-3651
pubmed: 23443812
pmcid: 3615209
Hofbauer, L. C. & Rauner, M. Minireview: live and let die: molecular effects of glucocorticoids on bone cells. Mol. Endocrinol. 23, 1525–1531 (2009).
doi: 10.1210/me.2009-0069
pubmed: 19477950
pmcid: 5419139
Compston, J. Glucocorticoid-induced osteoporosis: an update. Endocrine 61, 7–16 (2018).
doi: 10.1007/s12020-018-1588-2
pubmed: 29691807
pmcid: 5997116
Minetto, M. et al. Bone loss is more severe in primary adrenal than in pituitary-dependent Cushing’s syndrome. Osteoporos. Int. 15, 855–861 (2004).
doi: 10.1007/s00198-004-1616-3
pubmed: 15034643
Zhong, Q. et al. Multiple melanocortin receptors are expressed in bone cells. Bone 36, 820–831 (2005).
doi: 10.1016/j.bone.2005.01.020
pubmed: 15804492
Isales, C. M., Zaidi, M. & Blair, H. C. ACTH is a novel regulator of bone mass. Ann. N. Y. Acad. Sci. 1192, 110–116 (2010).
doi: 10.1111/j.1749-6632.2009.05231.x
pubmed: 20392225
Sato, T. et al. Bone phenotype in melanocortin 2 receptor-deficient mice. Bone Rep. 13, 100713 (2020).
doi: 10.1016/j.bonr.2020.100713
pubmed: 32964075
pmcid: 7490991
Zaidi, M. et al. ACTH protects against glucocorticoid-induced osteonecrosis of bone. Proc. Natl Acad. Sci. USA 107, 8782–8787 (2010).
doi: 10.1073/pnas.0912176107
pubmed: 20421485
pmcid: 2889316
Tourkova, I. L. et al. Adrenocorticotropic hormone and 1,25-dihydroxyvitamin D(3) enhance human osteogenesis in vitro by synergistically accelerating the expression of bone-specific genes. Lab. Invest. 97, 1072–1083 (2017).
doi: 10.1038/labinvest.2017.62
pubmed: 28737765
pmcid: 5844701
Sadeghi, F., Vahednia, E., Naderi Meshkin, H. & Kerachian, M. A. The effect of adrenocorticotropic hormone on alpha-2-macroglobulin in osteoblasts derived from human mesenchymal stem cells. J. Cell. Mol. Med. 24, 4784–4790 (2020).
doi: 10.1111/jcmm.15152
pubmed: 32163666
pmcid: 7176844
Elabd, C. et al. Oxytocin controls differentiation of human mesenchymal stem cells and reverses osteoporosis. Stem Cell 26, 2399–2407 (2008).
doi: 10.1634/stemcells.2008-0127
Tamma, R. et al. Oxytocin is an anabolic bone hormone. Proc. Natl Acad. Sci. USA 106, 7149–7154 (2009).
doi: 10.1073/pnas.0901890106
pubmed: 19369205
pmcid: 2678458
Sun, L. et al. Functions of vasopressin and oxytocin in bone mass regulation. Proc. Natl Acad. Sci. USA 113, 164–169 (2016).
doi: 10.1073/pnas.1523762113
pubmed: 26699482
Tamma, R. et al. Regulation of bone remodeling by vasopressin explains the bone loss in hyponatremia. Proc. Natl Acad. Sci. USA 110, 18644–18649 (2013).
doi: 10.1073/pnas.1318257110
pubmed: 24167258
pmcid: 3831977
Athonvarangkul, D. & Wysolmerski, J. J. Crosstalk within a brain–breast–bone axis regulates mineral and skeletal metabolism during lactation. Front. Physiol. 14, 1121579 (2023).
doi: 10.3389/fphys.2023.1121579
pubmed: 36875035
pmcid: 9979219
Di Benedetto, A. et al. Osteoblast regulation via ligand-activated nuclear trafficking of the oxytocin receptor. Proc. Natl Acad. Sci. USA 111, 16502–16507 (2014).
doi: 10.1073/pnas.1419349111
pubmed: 25378700
pmcid: 4246276
Sun, L. et al. Oxytocin regulates body composition. Proc. Natl Acad. Sci. USA 116, 26808–26815 (2019).
doi: 10.1073/pnas.1913611116
pubmed: 31843930
pmcid: 6936484
Liu, X. et al. Oxytocin deficiency impairs maternal skeletal remodeling. Biochem. Biophys. Res. Commun. 388, 161–166 (2009).
doi: 10.1016/j.bbrc.2009.07.148
pubmed: 19653998
Yu, W. J. et al. Association between serum oxytocin, bone mineral density and body composition in Chinese adult females. Medicina 58, 1625 (2022).
doi: 10.3390/medicina58111625
pubmed: 36422164
pmcid: 9695124
Breuil, V. et al. Oxytocin, a new determinant of bone mineral density in post-menopausal women: analysis of the OPUS cohort. J. Clin. Endocrinol. Metab. 99, E634–E641 (2014).
doi: 10.1210/jc.2013-4126
pubmed: 24446658
Breuil, V. et al. Oxytocin and bone status in men: analysis of the MINOS cohort. Osteoporos. Int. 26, 2877–2882 (2015).
doi: 10.1007/s00198-015-3201-3
pubmed: 26109496
Sejling, A. S., Pedersen-Bjergaard, U. & Eiken, P. Syndrome of inappropriate ADH secretion and severe osteoporosis. J. Clin. Endocrinol. Metab. 97, 4306–4310 (2012).
doi: 10.1210/jc.2012-2031
pubmed: 23076350
Sejling, A. S., Thorsteinsson, A. L., Pedersen-Bjergaard, U. & Eiken, P. Recovery from SIADH-associated osteoporosis: a case report. J. Clin. Endocrinol. Metab. 99, 3527–3530 (2014).
doi: 10.1210/jc.2014-1572
pubmed: 24971663
Murthy, K. et al. The effects of hyponatremia on bone density and fractures: a systematic review and meta-analysis. Endocr. Pract. 25, 366–378 (2019).
doi: 10.4158/EP-2018-0499
pubmed: 30720342
Upala, S. & Sanguankeo, A. Association between hyponatremia, osteoporosis, and fracture: a systematic review and meta-analysis. J. Clin. Endocrinol. Metab. 101, 1880–1886 (2016).
doi: 10.1210/jc.2015-4228
pubmed: 26913635
Kinsella, S., Moran, S., Sullivan, M. O., Molloy, M. G. & Eustace, J. A. Hyponatremia independent of osteoporosis is associated with fracture occurrence. Clin. J. Am. Soc. Nephrol. 5, 275–280 (2010).
doi: 10.2215/CJN.06120809
pubmed: 20056759
pmcid: 2827601
Coss, D. et al. Effects of prolactin on osteoblast alkaline phosphatase and bone formation in the developing rat. Am. J. Physiol. Endocrinol. Metab. 279, E1216–E1225 (2000).
doi: 10.1152/ajpendo.2000.279.6.E1216
pubmed: 11093907
Seriwatanachai, D. et al. Prolactin directly enhances bone turnover by raising osteoblast-expressed receptor activator of nuclear factor kappaB ligand/osteoprotegerin ratio. Bone 42, 535–546 (2008).
doi: 10.1016/j.bone.2007.11.008
pubmed: 18166509
Clement-Lacroix, P. et al. Osteoblasts are a new target for prolactin: analysis of bone formation in prolactin receptor knockout mice. Endocrinology 140, 96–105 (1999).
doi: 10.1210/endo.140.1.6436
pubmed: 9886812
Sowers, M. et al. Changes in body composition in women over six years at midlife: ovarian and chronological aging. J. Clin. Endocrinol. Metab. 92, 895–901 (2007).
doi: 10.1210/jc.2006-1393
pubmed: 17192296
Liu, X. M. et al. FSH regulates fat accumulation and redistribution in aging through the Galphai/Ca(2+)/CREB pathway. Aging Cell 14, 409–420 (2015).
doi: 10.1111/acel.12331
pubmed: 25754247
pmcid: 4406670
Han, X. et al. FSH promotes fat accumulation by activating PPARgamma signaling in surgically castrated, but not immunocastrated, male pigs. Theriogenology 160, 10–17 (2021).
doi: 10.1016/j.theriogenology.2020.10.029
pubmed: 33166850
Han, X. et al. A novel follicle-stimulating hormone vaccine for controlling fat accumulation. Theriogenology 148, 103–111 (2020).
doi: 10.1016/j.theriogenology.2020.03.005
pubmed: 32171969
Abildgaard, J. et al. Changes in abdominal subcutaneous adipose tissue phenotype following menopause is associated with increased visceral fat mass. Sci. Rep. 11, 14750 (2021).
doi: 10.1038/s41598-021-94189-2
pubmed: 34285301
pmcid: 8292317
Araujo, A. B. & Wittert, G. A. Endocrinology of the aging male. Best. Pract. Res. Clin. Endocrinol. Metab. 25, 303–319 (2011).
doi: 10.1016/j.beem.2010.11.004
pubmed: 21397200
pmcid: 3073592
Ostergren, P. B. et al. Metabolic consequences of gonadotropin-releasing hormone agonists vs orchiectomy: a randomized clinical study. BJU Int. 123, 602–611 (2019).
doi: 10.1111/bju.14609
pubmed: 30388320
Lundback, V., Kulyte, A., Dahlman, I. & Marcus, C. Adipose-specific inactivation of thyroid stimulating hormone receptors in mice modifies body weight, temperature and gene expression in adipocytes. Physiol. Rep. 8, e14538 (2020).
doi: 10.14814/phy2.14538
pubmed: 32812397
pmcid: 7435038
Draman, M. S. et al. The role of thyrotropin receptor activation in adipogenesis and modulation of fat phenotype. Front. Endocrinol. 8, 83 (2017).
doi: 10.3389/fendo.2017.00083
Lu, M. & Lin, R. Y. TSH stimulates adipogenesis in mouse embryonic stem cells. J. Endocrinol. 196, 159–169 (2008).
doi: 10.1677/JOE-07-0452
pubmed: 18180327
pmcid: 2692893
Endo, T. & Kobayashi, T. Expression of functional TSH receptor in white adipose tissues of hyt/hyt mice induces lipolysis in vivo. Am. J. Physiol. Endocrinol. Metab. 302, E1569–E1575 (2012).
doi: 10.1152/ajpendo.00572.2011
pubmed: 22496347
Kumar, S., Coenen, M. J., Scherer, P. E. & Bahn, R. S. Evidence for enhanced adipogenesis in the orbits of patients with Graves’ ophthalmopathy. J. Clin. Endocrinol. Metab. 89, 930–935 (2004).
doi: 10.1210/jc.2003-031427
pubmed: 14764816
Haraguchi, K., Shimura, H., Lin, L., Endo, T. & Onaya, T. Differentiation of rat preadipocytes is accompanied by expression of thyrotropin receptors. Endocrinology 137, 3200–3205 (1996).
doi: 10.1210/endo.137.8.8754740
pubmed: 8754740
Lu, S. et al. Role of extrathyroidal TSHR expression in adipocyte differentiation and its association with obesity. Lipids Health Dis. 11, 17 (2012).
doi: 10.1186/1476-511X-11-17
pubmed: 22289392
pmcid: 3285521
Haraguchi, K. et al. Effects of thyrotropin on the proliferation and differentiation of cultured rat preadipocytes. Thyroid 9, 613–619 (1999).
doi: 10.1089/thy.1999.9.613
pubmed: 10411125
Haluzik, M. et al. Effects of hypo- and hyperthyroidism on noradrenergic activity and glycerol concentrations in human subcutaneous abdominal adipose tissue assessed with microdialysis. J. Clin. Endocrinol. Metab. 88, 5605–5608 (2003).
doi: 10.1210/jc.2003-030576
pubmed: 14671140
Fox, C. S. et al. Relations of thyroid function to body weight: cross-sectional and longitudinal observations in a community-based sample. Arch. Intern. Med. 168, 587–592 (2008).
doi: 10.1001/archinte.168.6.587
pubmed: 18362250
Ittermann, T. et al. Low serum TSH levels are associated with low values of fat-free mass and body cell mass in the elderly. Sci. Rep. 11, 10547 (2021).
doi: 10.1038/s41598-021-90178-7
pubmed: 34006958
pmcid: 8131378
Dvorakova, M. et al. Relationship between pituitary–thyroid axis hormones and anthropometric parameters in Czech adult population. Physiol. Res. 57, S127–S134 (2008).
doi: 10.33549/physiolres.931497
pubmed: 18271684
Nyrnes, A., Jorde, R. & Sundsfjord, J. Serum TSH is positively associated with BMI. Int. J. Obes. 30, 100–105 (2006).
doi: 10.1038/sj.ijo.0803112
Ruhla, S. et al. A high normal TSH is associated with the metabolic syndrome. Clin. Endocrinol. 72, 696–701 (2010).
doi: 10.1111/j.1365-2265.2009.03698.x
Sakurai, M. et al. Association between a serum thyroid-stimulating hormone concentration within the normal range and indices of obesity in Japanese men and women. Intern. Med. 53, 669–674 (2014).
doi: 10.2169/internalmedicine.53.1387
pubmed: 24694474
Zhang, J. et al. TSH promotes adiposity by inhibiting the browning of white fat. Adipocyte 9, 264–278 (2020).
doi: 10.1080/21623945.2020.1783101
pubmed: 32579056
pmcid: 7469524
Jiang, D. et al. Thyroid-stimulating hormone inhibits adipose triglyceride lipase in 3T3-L1 adipocytes through the PKA pathway. PLoS ONE 10, e0116439 (2015).
doi: 10.1371/journal.pone.0116439
pubmed: 25590597
pmcid: 4295851
Janson, A. et al. Effects of stimulatory and inhibitory thyrotropin receptor antibodies on lipolysis in infant adipocytes. J. Clin. Endocrinol. Metab. 80, 1712–1716 (1995).
pubmed: 7745024
Endo, T. & Kobayashi, T. Thyroid-stimulating hormone receptor in brown adipose tissue is involved in the regulation of thermogenesis. Am. J. Physiol. Endocrinol. Metab. 295, E514–E518 (2008).
doi: 10.1152/ajpendo.90433.2008
pubmed: 18559984
Zhang, L. et al. Biological effects of thyrotropin receptor activation on human orbital preadipocytes. Invest. Ophthalmol. Vis. Sci. 47, 5197–5203 (2006).
doi: 10.1167/iovs.06-0596
pubmed: 17122103
Comas, F. et al. Adipose tissue TSH as a new modulator of human adipocyte mitochondrial function. Int. J. Obes. 43, 1611–1619 (2019).
doi: 10.1038/s41366-018-0203-1
Elgadi, A., Zemack, H., Marcus, C. & Norgren, S. Tissue-specific knockout of TSHr in white adipose tissue increases adipocyte size and decreases TSH-induced lipolysis. Biochem. Biophys. Res. Commun. 393, 526–530 (2010).
doi: 10.1016/j.bbrc.2010.02.042
pubmed: 20152797
Moreno-Navarrete, J. M. et al. TSHB mRNA is linked to cholesterol metabolism in adipose tissue. FASEB J. 31, 4482–4491 (2017).
doi: 10.1096/fj.201700161R
pubmed: 28646016
pmcid: 5602896
Blevins, J. E., Schwartz, M. W. & Baskin, D. G. Evidence that paraventricular nucleus oxytocin neurons link hypothalamic leptin action to caudal brain stem nuclei controlling meal size. Am. J. Physiol. Regul. Integr. Comp. Physiol. 287, R87–R96 (2004).
doi: 10.1152/ajpregu.00604.2003
pubmed: 15044184
Son, S. et al. Whole-brain wiring diagram of oxytocin system in adult mice. J. Neurosci. 42, 5021–5033 (2022).
doi: 10.1523/JNEUROSCI.0307-22.2022
pubmed: 35606144
pmcid: 9233446
Maejima, Y. et al. Oxytocinergic circuit from paraventricular and supraoptic nuclei to arcuate POMC neurons in hypothalamus. FEBS Lett. 588, 4404–4412 (2014).
doi: 10.1016/j.febslet.2014.10.010
pubmed: 25448678
Olson, B. R. et al. Oxytocin and an oxytocin agonist administered centrally decrease food intake in rats. Peptides 12, 113–118 (1991).
doi: 10.1016/0196-9781(91)90176-P
pubmed: 1646995
Arletti, R., Benelli, A. & Bertolini, A. Oxytocin inhibits food and fluid intake in rats. Physiol. Behav. 48, 825–830 (1990).
doi: 10.1016/0031-9384(90)90234-U
pubmed: 2087513
Smith, A. S., Korgan, A. C. & Young, W. S. Oxytocin delivered nasally or intraperitoneally reaches the brain and plasma of normal and oxytocin knockout mice. Pharmacol. Res. 146, 104324 (2019).
doi: 10.1016/j.phrs.2019.104324
pubmed: 31238093
pmcid: 6679720
Maejima, Y. et al. Peripheral oxytocin treatment ameliorates obesity by reducing food intake and visceral fat mass. Aging 3, 1169–1177 (2011).
doi: 10.18632/aging.100408
pubmed: 22184277
pmcid: 3273897
Klockars, A., Brunton, C., Li, L., Levine, A. S. & Olszewski, P. K. Intravenous administration of oxytocin in rats acutely decreases deprivation-induced chow intake, but it fails to affect consumption of palatable solutions. Peptides 93, 13–19 (2017).
doi: 10.1016/j.peptides.2017.04.010
pubmed: 28460894
Wronski, M. L. et al. A randomized, double-blind, placebo-controlled clinical trial of 8-week intranasal oxytocin administration in adults with obesity: rationale, study design, and methods. Contemp. Clin. Trials 122, 106909 (2022).
doi: 10.1016/j.cct.2022.106909
pubmed: 36087842
pmcid: 10329413
Wu, Z. et al. An obligate role of oxytocin neurons in diet induced energy expenditure. PLoS ONE 7, e45167 (2012).
doi: 10.1371/journal.pone.0045167
pubmed: 23028821
pmcid: 3445456
Deblon, N. et al. Mechanisms of the anti-obesity effects of oxytocin in diet-induced obese rats. PLoS ONE 6, e25565 (2011).
doi: 10.1371/journal.pone.0025565
pubmed: 21980491
pmcid: 3181274
Yi, K. J. et al. The regulation of oxytocin receptor gene expression during adipogenesis. J. Neuroendocrinol. 27, 335–342 (2015).
doi: 10.1111/jne.12268
pubmed: 25702774
Blevins, J. E. et al. Chronic oxytocin administration inhibits food intake, increases energy expenditure, and produces weight loss in fructose-fed obese rhesus monkeys. Am. J. Physiol. Regul. Integr. Comp. Physiol. 308, R431–R438 (2015).
doi: 10.1152/ajpregu.00441.2014
pubmed: 25540103
Yuan, J., Zhang, R., Wu, R., Gu, Y. & Lu, Y. The effects of oxytocin to rectify metabolic dysfunction in obese mice are associated with increased thermogenesis. Mol. Cell Endocrinol. 514, 110903 (2020).
doi: 10.1016/j.mce.2020.110903
pubmed: 32531419
Noble, E. E., Billington, C. J., Kotz, C. M. & Wang, C. Oxytocin in the ventromedial hypothalamic nucleus reduces feeding and acutely increases energy expenditure. Am. J. Physiol. Regul. Integr. Comp. Physiol. 307, R737–R745 (2014).
doi: 10.1152/ajpregu.00118.2014
pubmed: 24990860
pmcid: 4166752
Kasahara, Y. et al. Oxytocin receptor in the hypothalamus is sufficient to rescue normal thermoregulatory function in male oxytocin receptor knockout mice. Endocrinology 154, 4305–4315 (2013).
doi: 10.1210/en.2012-2206
pubmed: 24002032
Xi, D. et al. Ablation of oxytocin neurons causes a deficit in cold stress response. J. Endocr. Soc. 1, 1041–1055 (2017).
doi: 10.1210/js.2017-00136
pubmed: 29264556
pmcid: 5686635
Qian, W. et al. Decreased circulating levels of oxytocin in obesity and newly diagnosed type 2 diabetic patients. J. Clin. Endocrinol. Metab. 99, 4683–4689 (2014).
doi: 10.1210/jc.2014-2206
pubmed: 25233153
Froemke, R. C. & Young, L. J. Oxytocin, neural plasticity, and social behavior. Annu. Rev. Neurosci. 44, 359–381 (2021).
doi: 10.1146/annurev-neuro-102320-102847
pubmed: 33823654
pmcid: 8604207
Stevens, F. L., Weisman, O., Feldman, R., Hurley, R. A. & Taber, K. H. Oxytocin and behavior: evidence for effects in the brain. J. Neuropsychiatry Clin. Neurosci. 25, 96–102 (2013).
doi: 10.1176/appi.neuropsych.13030061
pubmed: 23686025
Gainer, H. Cell-type specific expression of oxytocin and vasopressin genes: an experimental odyssey. J. Neuroendocrinol. 24, 528–538 (2012).
doi: 10.1111/j.1365-2826.2011.02236.x
pubmed: 21985498
pmcid: 3262921
Eliava, M. et al. A new population of parvocellular oxytocin neurons controlling magnocellular neuron activity and inflammatory pain processing. Neuron 89, 1291–1304 (2016).
doi: 10.1016/j.neuron.2016.01.041
pubmed: 26948889
pmcid: 5679079
Ishunina, T. A. & Swaab, D. F. Vasopressin and oxytocin neurons of the human supraoptic and paraventricular nucleus: size changes in relation to age and sex. J. Clin. Endocrinol. Metab. 84, 4637–4644 (1999).
doi: 10.1210/jcem.84.12.6187
pubmed: 10599731
Yoshikawa, T. et al. Spatiotemporal profiles of arginine vasopressin transcription in cultured suprachiasmatic nucleus. Eur. J. Neurosci. 42, 2678–2689 (2015).
doi: 10.1111/ejn.13061
pubmed: 26342201
Jenkins, J. S., Ang, V. T., Hawthorn, J., Rossor, M. N. & Iversen, L. L. Vasopressin, oxytocin and neurophysins in the human brain and spinal cord. Brain Res. 291, 111–117 (1984).
doi: 10.1016/0006-8993(84)90656-5
pubmed: 6697176
Mens, W. B., Witter, A. & Van Wimersma Greidanus, T. B. Penetration of neurohypophyseal hormones from plasma into cerebrospinal fluid (CSF): half-times of disappearance of these neuropeptides from CSF. Brain Res. 262, 143–149 (1983).
doi: 10.1016/0006-8993(83)90478-X
pubmed: 6831225
Pow, D. V. & Morris, J. F. Dendrites of hypothalamic magnocellular neurons release neurohypophyseal peptides by exocytosis. Neuroscience 32, 435–439 (1989).
doi: 10.1016/0306-4522(89)90091-2
pubmed: 2586758
Hirasawa, M. et al. Dendritically released transmitters cooperate via autocrine and retrograde actions to inhibit afferent excitation in rat brain. J. Physiol. 559, 611–624 (2004).
doi: 10.1113/jphysiol.2004.066159
pubmed: 15254151
pmcid: 1665137
Brussaard, A. B., Kits, K. S. & de Vlieger, T. A. Postsynaptic mechanism of depression of GABAergic synapses by oxytocin in the supraoptic nucleus of immature rat. J. Physiol. 497, 495–507 (1996).
doi: 10.1113/jphysiol.1996.sp021783
pubmed: 8961190
pmcid: 1160999
Carter, C. S. Oxytocin pathways and the evolution of human behavior. Annu. Rev. Psychol. 65, 17–39 (2014).
doi: 10.1146/annurev-psych-010213-115110
pubmed: 24050183
Carter, C. S. et al. Is oxytocin ‘Nature’s Medicine’? Pharmacol. Rev. 72, 829–861 (2020).
doi: 10.1124/pr.120.019398
pubmed: 32912963
pmcid: 7495339
Cochran, D. M., Fallon, D., Hill, M. & Frazier, J. A. The role of oxytocin in psychiatric disorders: a review of biological and therapeutic research findings. Harv. Rev. Psychiatry 21, 219–247 (2013).
doi: 10.1097/HRP.0b013e3182a75b7d
pubmed: 24651556
pmcid: 4120070
Ryu, V. et al. Brain atlas for glycoprotein hormone receptors at single-transcript level. eLife 11, e79612 (2022).
doi: 10.7554/eLife.79612
pubmed: 36052994
pmcid: 9473692
Fonseca, T. L. et al. Coordination of hypothalamic and pituitary T3 production regulates TSH expression. J. Clin. Invest. 123, 1492–1500 (2013).
doi: 10.1172/JCI61231
pubmed: 23524969
pmcid: 3613903
Sáenz de Miera, C., Sage-Ciocca, D., Simonneaux, V., Pévet, P. & Monecke, S. Melatonin-independent photoperiodic entrainment of the circannual TSH rhythm in the pars tuberalis of the European Hamster. J. Biol. Rhythm. 33, 302–317 (2018).
doi: 10.1177/0748730418766601
Hanon, E. A. et al. Ancestral TSH mechanism signals summer in a photoperiodic mammal. Curr. Biol. 18, 1147–1152 (2008).
doi: 10.1016/j.cub.2008.06.076
pubmed: 18674911
Barrett, P. & Bolborea, M. Molecular pathways involved in seasonal body weight and reproductive responses governed by melatonin. J. Pineal Res. 52, 376–388 (2012).
doi: 10.1111/j.1600-079X.2011.00963.x
pubmed: 22017374
Ikegami, K. et al. Tissue-specific posttranslational modification allows functional targeting of thyrotropin. Cell Rep. 9, 801–810 (2014).
doi: 10.1016/j.celrep.2014.10.006
pubmed: 25437536
pmcid: 4251493
Prevot, V. et al. The versatile tanycyte: a hypothalamic integrator of reproduction and energy metabolism. Endocr. Rev. 39, 333–368 (2018).
doi: 10.1210/er.2017-00235
pubmed: 29351662
Yang, R. et al. Association of subclinical hypothyroidism with anxiety symptom in young first-episode and drug-naive patients with major depressive disorder. Front. Psychiatry 13, 920723 (2022).
doi: 10.3389/fpsyt.2022.920723
pubmed: 35815037
pmcid: 9263214
Dayan, C. M. & Panicker, V. Hypothyroidism and depression. Eur. Thyroid J. 2, 168–179 (2013).
doi: 10.1159/000353777
pubmed: 24847450
pmcid: 4017747
Luan, S. et al. Thyrotropin receptor signaling deficiency impairs spatial learning and memory in mice. J. Endocrinol. 246, 41–55 (2020).
doi: 10.1530/JOE-20-0026
pubmed: 32420901
Burgos, J. R., Iresjo, B. M., Warnaker, S. & Smedh, U. Presence of TSH receptors in discrete areas of the hypothalamus and caudal brainstem with relevance for feeding controls — support for functional significance. Brain Res. 1642, 278–286 (2016).
doi: 10.1016/j.brainres.2016.04.007
pubmed: 27059392
Bi, W. K. et al. FSH signaling is involved in affective disorders. Biochem. Biophys. Res. Commun. 525, 915–920 (2020).
doi: 10.1016/j.bbrc.2020.03.039
pubmed: 32171529
Blair, J. A., Bhatta, S. & Casadesus, G. CNS luteinizing hormone receptor activation rescues ovariectomy-related loss of spatial memory and neuronal plasticity. Neurobiol. Aging 78, 111–120 (2019).
doi: 10.1016/j.neurobiolaging.2019.02.002
pubmed: 30925299
pmcid: 6545150
Gale, S. D., Baxter, L. & Thompson, J. Greater memory impairment in dementing females than males relative to sex-matched healthy controls. J. Clin. Exp. Neuropsychol. 38, 527–533 (2016).
doi: 10.1080/13803395.2015.1132298
pubmed: 26735615
pmcid: 4967933
Chêne, G. et al. Gender and incidence of dementia in the Framingham Heart Study from mid-adult life. Alzheimers Dement. 11, 310–320 (2015).
doi: 10.1016/j.jalz.2013.10.005
pubmed: 24418058
Lin, K. A. et al. Marked gender differences in progression of mild cognitive impairment over 8 years. Alzheimers Dement. 1, 103–110 (2015).
doi: 10.1016/j.trci.2015.07.001
Shumaker, S. A. et al. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women’s Health Initiative Memory Study. JAMA 291, 2947–2958 (2004).
doi: 10.1001/jama.291.24.2947
pubmed: 15213206
Espeland, M. A. et al. Conjugated equine estrogens and global cognitive function in postmenopausal women: Women’s Health Initiative Memory Study. JAMA 291, 2959–2968 (2004).
doi: 10.1001/jama.291.24.2959
pubmed: 15213207
Zandi, P. P. et al. Hormone replacement therapy and incidence of Alzheimer disease in older women: the Cache County Study. JAMA 288, 2123–2129 (2002).
doi: 10.1001/jama.288.17.2123
pubmed: 12413371
Greendale, G. A. et al. Menopause-associated symptoms and cognitive performance: results from the study of women’s health across the nation. Am. J. Epidemiol. 171, 1214–1224 (2010).
doi: 10.1093/aje/kwq067
pubmed: 20442205
pmcid: 2915492
Bowen, R. L., Isley, J. P. & Atkinson, R. L. An association of elevated serum gonadotropin concentrations and Alzheimer disease? J. Neuroendocrinol. 12, 351–354 (2000).
doi: 10.1046/j.1365-2826.2000.00461.x
pubmed: 10718932
Short, R. A., Bowen, R. L., O’Brien, P. C. & Graff-Radford, N. R. Elevated gonadotropin levels in patients with Alzheimer disease. Mayo Clin. Proc. 76, 906–909 (2001).
doi: 10.1016/S0025-6196(11)62109-5
pubmed: 11560301
Corbo, R. M., Gambina, G., Broggio, E. & Scacchi, R. Influence of variation in the follicle-stimulating hormone receptor gene (FSHR) and age at menopause on the development of Alzheimer’s disease in women. Dement. Geriatr. Cogn. Disord. 32, 63–69 (2011).
doi: 10.1159/000330472
pubmed: 21865747
Espinoza, S. E. et al. Intranasal oxytocin improves lean muscle mass and lowers LDL cholesterol in older adults with sarcopenic obesity: a pilot randomized controlled trial. J. Am. Med. Dir. Assoc. 22, 1877–1882 (2021).
doi: 10.1016/j.jamda.2021.04.015
pubmed: 34029521
pmcid: 8567747
Zhu, L. L. et al. Blocking FSH action attenuates osteoclastogenesis. Biochem. Biophys. Res. Commun. 422, 54–58 (2012).
doi: 10.1016/j.bbrc.2012.04.104
pubmed: 22561017
pmcid: 4219240
Rojekar, S. et al. Development and biophysical characterization of a humanized FSH-blocking monoclonal antibody therapeutic formulated at an ultra-high concentration. eLife 12, e88898 (2023).
doi: 10.7554/eLife.88898
pubmed: 37334968
pmcid: 10325703
Sant, D., Rokekar, S. & Gera, S. Optimizing therapeutic humanized FSH-blocking antibody formulation using protein thermal shift assay. Ann. N. Y. Acad. Sci. 1521, 67–78 (2023).
doi: 10.1111/nyas.14952
pubmed: 36628526
Geng, W. et al. Immunization with FSHbeta fusion protein antigen prevents bone loss in a rat ovariectomy-induced osteoporosis model. Biochem. Biophys. Res. Commun. 434, 280–286 (2013).
doi: 10.1016/j.bbrc.2013.02.116
pubmed: 23537645