Cargando…

Androgen receptor signaling regulates follicular growth and steroidogenesis in interaction with gonadotropins in the ovary during mini-puberty in mice

In females, androgens contribute to ovarian diseases such as polycystic ovarian syndrome (PCOS), but their action is also crucial for ovarian physiology, i.e., follicular growth and estradiol (E2) synthesis during reproductive life, in interaction with the gonadotropins LH and FSH. However, it is un...

Descripción completa

Detalles Bibliográficos
Autores principales: Devillers, Marie M., François, Charlotte M., Chester, Mélanie, Corre, Raphaël, Cluzet, Victoria, Giton, Frank, Cohen-Tannoudji, Joëlle, Guigon, Céline J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10154677/
https://www.ncbi.nlm.nih.gov/pubmed/37152943
http://dx.doi.org/10.3389/fendo.2023.1130681
_version_ 1785036177245470720
author Devillers, Marie M.
François, Charlotte M.
Chester, Mélanie
Corre, Raphaël
Cluzet, Victoria
Giton, Frank
Cohen-Tannoudji, Joëlle
Guigon, Céline J.
author_facet Devillers, Marie M.
François, Charlotte M.
Chester, Mélanie
Corre, Raphaël
Cluzet, Victoria
Giton, Frank
Cohen-Tannoudji, Joëlle
Guigon, Céline J.
author_sort Devillers, Marie M.
collection PubMed
description In females, androgens contribute to ovarian diseases such as polycystic ovarian syndrome (PCOS), but their action is also crucial for ovarian physiology, i.e., follicular growth and estradiol (E2) synthesis during reproductive life, in interaction with the gonadotropins LH and FSH. However, it is unclear whether androgens already play a role in the ovary at mini-puberty, a phase of postnatal development with active follicular growth and high E2 levels. Therefore, we analyzed the potential actions of androgens on the ovary and their possible interaction with gonadotropins during this period in mice. We used molecular-based studies and pharmacological approaches in vivo and on cultured ovaries. We found that mini-pubertal ovaries produce significant amounts of testosterone and display androgen receptor (AR) expression in growing follicles, both under the control of LH. By blocking AR signaling either in vivo or in ovarian cultures, we found that this pathway may participate in the regulation of prepubertal E2 synthesis and follicular growth, possibly by regulating the expression of a number of key intra-ovarian regulators, including FSH receptor (Fshr), the aromatase enzyme converting androgens into estrogens (Cyp19a1) and the cell cycle inhibitor p27KIP1 (Cdkn1b). We further showed that AR may stimulate FSH-mediated regulation of Cyp19a1 through its action on Fshr mRNA abundance. Overall, this work supports the idea that AR signaling is already activated in mini-pubertal ovaries to regulate E2 synthesis and follicular growth, at the interplay with LH and FSH signaling. Its early action may, thus, contribute to the implementation of early ovarian function with possible impacts on reproductive function.
format Online
Article
Text
id pubmed-10154677
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-101546772023-05-04 Androgen receptor signaling regulates follicular growth and steroidogenesis in interaction with gonadotropins in the ovary during mini-puberty in mice Devillers, Marie M. François, Charlotte M. Chester, Mélanie Corre, Raphaël Cluzet, Victoria Giton, Frank Cohen-Tannoudji, Joëlle Guigon, Céline J. Front Endocrinol (Lausanne) Endocrinology In females, androgens contribute to ovarian diseases such as polycystic ovarian syndrome (PCOS), but their action is also crucial for ovarian physiology, i.e., follicular growth and estradiol (E2) synthesis during reproductive life, in interaction with the gonadotropins LH and FSH. However, it is unclear whether androgens already play a role in the ovary at mini-puberty, a phase of postnatal development with active follicular growth and high E2 levels. Therefore, we analyzed the potential actions of androgens on the ovary and their possible interaction with gonadotropins during this period in mice. We used molecular-based studies and pharmacological approaches in vivo and on cultured ovaries. We found that mini-pubertal ovaries produce significant amounts of testosterone and display androgen receptor (AR) expression in growing follicles, both under the control of LH. By blocking AR signaling either in vivo or in ovarian cultures, we found that this pathway may participate in the regulation of prepubertal E2 synthesis and follicular growth, possibly by regulating the expression of a number of key intra-ovarian regulators, including FSH receptor (Fshr), the aromatase enzyme converting androgens into estrogens (Cyp19a1) and the cell cycle inhibitor p27KIP1 (Cdkn1b). We further showed that AR may stimulate FSH-mediated regulation of Cyp19a1 through its action on Fshr mRNA abundance. Overall, this work supports the idea that AR signaling is already activated in mini-pubertal ovaries to regulate E2 synthesis and follicular growth, at the interplay with LH and FSH signaling. Its early action may, thus, contribute to the implementation of early ovarian function with possible impacts on reproductive function. Frontiers Media S.A. 2023-04-19 /pmc/articles/PMC10154677/ /pubmed/37152943 http://dx.doi.org/10.3389/fendo.2023.1130681 Text en Copyright © 2023 Devillers, François, Chester, Corre, Cluzet, Giton, Cohen-Tannoudji and Guigon https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Devillers, Marie M.
François, Charlotte M.
Chester, Mélanie
Corre, Raphaël
Cluzet, Victoria
Giton, Frank
Cohen-Tannoudji, Joëlle
Guigon, Céline J.
Androgen receptor signaling regulates follicular growth and steroidogenesis in interaction with gonadotropins in the ovary during mini-puberty in mice
title Androgen receptor signaling regulates follicular growth and steroidogenesis in interaction with gonadotropins in the ovary during mini-puberty in mice
title_full Androgen receptor signaling regulates follicular growth and steroidogenesis in interaction with gonadotropins in the ovary during mini-puberty in mice
title_fullStr Androgen receptor signaling regulates follicular growth and steroidogenesis in interaction with gonadotropins in the ovary during mini-puberty in mice
title_full_unstemmed Androgen receptor signaling regulates follicular growth and steroidogenesis in interaction with gonadotropins in the ovary during mini-puberty in mice
title_short Androgen receptor signaling regulates follicular growth and steroidogenesis in interaction with gonadotropins in the ovary during mini-puberty in mice
title_sort androgen receptor signaling regulates follicular growth and steroidogenesis in interaction with gonadotropins in the ovary during mini-puberty in mice
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10154677/
https://www.ncbi.nlm.nih.gov/pubmed/37152943
http://dx.doi.org/10.3389/fendo.2023.1130681
work_keys_str_mv AT devillersmariem androgenreceptorsignalingregulatesfolliculargrowthandsteroidogenesisininteractionwithgonadotropinsintheovaryduringminipubertyinmice
AT francoischarlottem androgenreceptorsignalingregulatesfolliculargrowthandsteroidogenesisininteractionwithgonadotropinsintheovaryduringminipubertyinmice
AT chestermelanie androgenreceptorsignalingregulatesfolliculargrowthandsteroidogenesisininteractionwithgonadotropinsintheovaryduringminipubertyinmice
AT correraphael androgenreceptorsignalingregulatesfolliculargrowthandsteroidogenesisininteractionwithgonadotropinsintheovaryduringminipubertyinmice
AT cluzetvictoria androgenreceptorsignalingregulatesfolliculargrowthandsteroidogenesisininteractionwithgonadotropinsintheovaryduringminipubertyinmice
AT gitonfrank androgenreceptorsignalingregulatesfolliculargrowthandsteroidogenesisininteractionwithgonadotropinsintheovaryduringminipubertyinmice
AT cohentannoudjijoelle androgenreceptorsignalingregulatesfolliculargrowthandsteroidogenesisininteractionwithgonadotropinsintheovaryduringminipubertyinmice
AT guigoncelinej androgenreceptorsignalingregulatesfolliculargrowthandsteroidogenesisininteractionwithgonadotropinsintheovaryduringminipubertyinmice