Neurotensin: A novel mediator of ovulation?
angiogenesis
fertility
ovary
primate
sortilin
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
19
11
2020
revised:
11
02
2021
accepted:
12
02
2021
entrez:
12
3
2021
pubmed:
13
3
2021
medline:
16
7
2021
Statut:
ppublish
Résumé
The midcycle luteinizing hormone (LH) surge initiates a cascade of events within the ovarian follicle which culminates in ovulation. Only mural granulosa cells and theca cells express large numbers of LH receptors, and LH-stimulated paracrine mediators communicate the ovulatory signal within the follicle. Recent reports identified the neuropeptide neurotensin (NTS) as a product of granulosa cells. Here, we demonstrate that granulosa cells were the primary site of NTS expression in macaque ovulatory follicles. Granulosa cell NTS mRNA and protein increased after human chorionic gonadotropin (hCG) administration, which substitutes for the LH surge. To identify ovulatory actions of NTS, a NTS-neutralizing antibody was injected into preovulatory macaque follicles. hCG administration immediately followed, and ovaries were removed 48 hours later to evaluate ovulatory events. Follicles injected with control IgG ovulated normally. In contrast, 75% of NTS antibody-injected follicles failed to ovulate, containing oocytes trapped within unruptured, hemorrhagic follicles. Serum progesterone was unchanged. Of the three NTS receptors, SORT1 was highly expressed in follicular granulosa, theca, and endothelial cells; NTSR1 and NTSR2 were expressed at lower levels. Excessive blood cells in NTS antibody-injected follicles indicated vascular anomalies, so the response of monkey ovarian endothelial cells to NTS was evaluated in vitro. NTS stimulated endothelial cell migration and capillary sprout formation, consistent with a role for NTS in vascular remodeling associated with ovulation. In summary, we identified NTS as a possible paracrine mediator of ovulation. Further investigation of the NTS synthesis/response pathway may lead to improved treatments for infertility and novel targets for contraception.
Identifiants
pubmed: 33710668
doi: 10.1096/fj.202002547RR
pmc: PMC8314182
mid: NIHMS1715439
doi:
Substances chimiques
Chorionic Gonadotropin
0
Neurotensin
39379-15-2
Luteinizing Hormone
9002-67-9
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e21481Subventions
Organisme : NICHD NIH HHS
ID : P01 HD071875
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD097675
Pays : United States
Informations de copyright
© 2021 Federation of American Societies for Experimental Biology.
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