Transcriptional comparison of testicular adrenal rest tumors with fetal and adult tissues.
Journal
European journal of endocrinology
ISSN: 1479-683X
Titre abrégé: Eur J Endocrinol
Pays: England
ID NLM: 9423848
Informations de publication
Date de publication:
01 Nov 2022
01 Nov 2022
Historique:
received:
16
02
2022
accepted:
26
08
2022
pubmed:
2
9
2022
medline:
4
10
2022
entrez:
1
9
2022
Statut:
epublish
Résumé
Testicular adrenal rest tumors (TART) are a common complication of unknown cellular origin in patients with congenital adrenal hyperplasia (CAH). These benign tumors have both adrenal and testicular characteristics and are hypothesized to either derive from cells of adrenal origin from the fetal adrenogonadal primordium or by atypical differentiation of adult Leydig-progenitor cells. This study aims to unravel the identity and etiology of TART. Co-expression of adrenal-specific CYP11B1 and Leydig cell-specific HSD17B3 in TART was studied using immunohistochemistry. We studied the possibility of TART being derived from atypical differentiation of adult Leydig-progenitor cells by the quantification of adrenal-specific enzyme expression upon adrenocorticotrophic hormone (ACTH)-like stimulation of ex vivo cultured platelet-derived growth factor receptor alpha-positive cells. By comparing the transcriptome of TART (n = 16) with the transcriptome of fetal adrenal (n = 13), fetal testis (n = 5), adult adrenal (n = 11), and adult testis (n = 10) tissues, we explored the identity of TART. We demonstrate co-expression of adrenal-specific CYP11B1 and testis-specific HSD17B3 in TART cells, indicating the existence of a distinct TART cell exhibiting both adrenal and testicular characteristics. Ex vivo cultured adult Leydig-progenitor cells did not express the ACTH-receptor MC2R but did express CYP11B1 upon stimulation. Unsupervised clustering of transcriptome data showed that TART was most similar to adult adrenal tissue, followed by adult testis tissue, and least similar to either fetal tissue. Our data suggest that TART is induced - most likely via activation of a cAMP/protein kinase A-dependent receptor - from a progenitor cell into a unique mature adrenal-like cell type, sometimes exhibiting both adrenal and testicular features.
Sections du résumé
Background
UNASSIGNED
Testicular adrenal rest tumors (TART) are a common complication of unknown cellular origin in patients with congenital adrenal hyperplasia (CAH). These benign tumors have both adrenal and testicular characteristics and are hypothesized to either derive from cells of adrenal origin from the fetal adrenogonadal primordium or by atypical differentiation of adult Leydig-progenitor cells.
Objective
UNASSIGNED
This study aims to unravel the identity and etiology of TART.
Methods
UNASSIGNED
Co-expression of adrenal-specific CYP11B1 and Leydig cell-specific HSD17B3 in TART was studied using immunohistochemistry. We studied the possibility of TART being derived from atypical differentiation of adult Leydig-progenitor cells by the quantification of adrenal-specific enzyme expression upon adrenocorticotrophic hormone (ACTH)-like stimulation of ex vivo cultured platelet-derived growth factor receptor alpha-positive cells. By comparing the transcriptome of TART (n = 16) with the transcriptome of fetal adrenal (n = 13), fetal testis (n = 5), adult adrenal (n = 11), and adult testis (n = 10) tissues, we explored the identity of TART.
Results
UNASSIGNED
We demonstrate co-expression of adrenal-specific CYP11B1 and testis-specific HSD17B3 in TART cells, indicating the existence of a distinct TART cell exhibiting both adrenal and testicular characteristics. Ex vivo cultured adult Leydig-progenitor cells did not express the ACTH-receptor MC2R but did express CYP11B1 upon stimulation. Unsupervised clustering of transcriptome data showed that TART was most similar to adult adrenal tissue, followed by adult testis tissue, and least similar to either fetal tissue.
Conclusion
UNASSIGNED
Our data suggest that TART is induced - most likely via activation of a cAMP/protein kinase A-dependent receptor - from a progenitor cell into a unique mature adrenal-like cell type, sometimes exhibiting both adrenal and testicular features.
Identifiants
pubmed: 36047744
doi: 10.1530/EJE-22-0143
pmc: PMC7613903
mid: EMS157771
doi:
Substances chimiques
Adrenocorticotropic Hormone
9002-60-2
Steroid 11-beta-Hydroxylase
EC 1.14.15.4
Receptors, Platelet-Derived Growth Factor
EC 2.7.10.1
Cyclic AMP-Dependent Protein Kinases
EC 2.7.11.11
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
607-615Subventions
Organisme : Medical Research Council
ID : G1100357
Pays : United Kingdom
Références
Trends Endocrinol Metab. 2008 Sep;19(7):231-8
pubmed: 18691899
Nat Rev Endocrinol. 2021 Jul;17(7):421-434
pubmed: 34011989
Front Endocrinol (Lausanne). 2017 Mar 23;8:52
pubmed: 28386245
Reprod Domest Anim. 2015 Dec;50(6):1032-8
pubmed: 26482643
Am J Physiol. 1999 Feb;276(2):E303-9
pubmed: 9950790
Mol Cell Endocrinol. 2014 Mar 5;383(1-2):111-7
pubmed: 24325867
J Clin Endocrinol Metab. 2015 Mar;100(3):E524-30
pubmed: 25485724
J Clin Endocrinol Metab. 1994 Nov;79(5):1390-4
pubmed: 7962333
Science. 2015 Jan 23;347(6220):1260419
pubmed: 25613900
Endocr Rev. 2022 Jan 12;43(1):91-159
pubmed: 33961029
Mol Hum Reprod. 2014 Jun;20(6):476-88
pubmed: 24598113
J Pediatr Adolesc Gynecol. 2017 Oct;30(5):520-534
pubmed: 28450075
Am J Dis Child. 1963 Sep;106:243-50
pubmed: 14057603
Front Endocrinol (Lausanne). 2016 May 09;7:39
pubmed: 27242663
Endocrinology. 2003 Aug;144(8):3279-84
pubmed: 12865302
Genome Biol. 2014;15(12):550
pubmed: 25516281
Int J Androl. 2006 Feb;29(1):90-5; discussion 105-8
pubmed: 16466528
Eur J Endocrinol. 2015 Apr;172(4):491-9
pubmed: 25609776
Horm Res Paediatr. 2011 Feb;75(2):90-3
pubmed: 20664187
Cell Rep. 2019 Feb 5;26(6):1501-1517.e4
pubmed: 30726734
J Clin Endocrinol Metab. 2007 Sep;92(9):3674-80
pubmed: 17595257
Endocr Rev. 2019 Aug 1;40(4):973-987
pubmed: 30882882
Fertil Steril. 2008 Mar;89(3):597-601
pubmed: 17543962
Nat Cell Biol. 2020 Dec;22(12):1436-1446
pubmed: 33257808
Nat Rev Endocrinol. 2015 Jan;11(1):14-28
pubmed: 25287283
J Clin Endocrinol Metab. 2017 Feb 01;102(2):339-344
pubmed: 27901643
Front Endocrinol (Lausanne). 2021 Sep 20;12:730947
pubmed: 34616364
Eur J Endocrinol. 1999 Sep;141(3):231-7
pubmed: 10474120
Dev Biol. 2006 Nov 1;299(1):250-6
pubmed: 16949566
Nat Genet. 1994 May;7(1):34-9
pubmed: 8075637
Endocr Connect. 2017 Nov;6(8):866-875
pubmed: 29038332
J Clin Endocrinol Metab. 1990 May;70(5):1408-13
pubmed: 2335578
Hum Reprod. 2019 Sep 29;34(9):1621-1631
pubmed: 31398257