title: A novel action of follicle-stimulating hormone in the ovary promotes estradiol production without inducing excessive follicular growth before puberty.
abstract: In cyclic females, FSH stimulates ovarian estradiol (E2) production and follicular growth up to the terminal stage. A transient elevation in circulating FSH and E2 levels occurs shortly after birth. But what could be the action of FSH on the ovary during this period, and in particular how it stimulates ovarian steroidogenesis without supporting terminal follicular maturation is intriguing. By experimentally manipulating FSH levels, we demonstrate in mice that the mid-infantile elevation in FSH is mandatory for E2 production by the immature ovary, but that it does not stimulate follicle growth. Importantly, FSH increases aromatase expression to stimulate E2 synthesis, however it becomes unable to induce cyclin D2, a major driver of granulosa cell proliferation. Besides, although FSH prematurely induces luteinizing hormone (LH) receptor expression in granulosa cells, LH pathway is not functional in these cells to induce their terminal differentiation. In line with these results, supplying infantile mice with a superovulation regimen exacerbates E2 production, but it does not stimulate the growth of follicles and it does not induce ovulation. Overall, our findings unveil a regulation whereby high postnatal FSH concentrations ensure the supply of E2 required for programming adult reproductive function without inducing follicular maturation before puberty.
authors.affiliation: Sorbonne Paris Cité, Université Paris-Diderot, CNRS, INSERM, Biologie Fonctionnelle et Adaptative UMR 8251, Physiologie de l'Axe Gonadotrope U1133, Paris, France.
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: François
authors.affiliation: Sorbonne Paris Cité, Université Paris-Diderot, CNRS, INSERM, Biologie Fonctionnelle et Adaptative UMR 8251, Physiologie de l'Axe Gonadotrope U1133, Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Petit
authors.affiliation: APHP CIB GHU Sud Henri Mondor, INSERM IMRB U955, Eq.07, Faculté de Médecine, Creteil, France.
authors.forename: Frank
authors.initials: F
authors.lastname: Giton
authors.affiliation: Inserm U1052, CRCL, Faculté de Médecine Laennec, Lyon, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Gougeon
authors.affiliation: CHU de Rennes - Université de Rennes 1, Laboratoire de Biologie de la Reproduction, INSERM U1085-IRSET, France.
authors.forename: Célia
authors.initials: C
authors.lastname: Ravel
authors.affiliation: Sorbonne Paris Cité, Université Paris-Diderot, CNRS, INSERM, Biologie Fonctionnelle et Adaptative UMR 8251, Physiologie de l'Axe Gonadotrope U1133, Paris, France.
authors.forename: Solange
authors.initials: S
authors.lastname: Magre
authors.affiliation: Sorbonne Paris Cité, Université Paris-Diderot, CNRS, INSERM, Biologie Fonctionnelle et Adaptative UMR 8251, Physiologie de l'Axe Gonadotrope U1133, Paris, France.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Cohen-Tannoudji
authors.affiliation: Sorbonne Paris Cité, Université Paris-Diderot, CNRS, INSERM, Biologie Fonctionnelle et Adaptative UMR 8251, Physiologie de l'Axe Gonadotrope U1133, Paris, France.
authors.forename: Céline J
authors.initials: CJ
authors.lastname: Guigon
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001141:Aromatase / Q000378:metabolism; D056742:Cyclin D2 / Q000378:metabolism; D004958:Estradiol / Q000096:biosynthesis*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D006062:Gonadotropins / Q000494:pharmacology; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007223:Infant; D007986:Luteinizing Hormone / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D006080:Ovarian Follicle / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D011974:Receptors, LH / Q000378:metabolism; D012741:Sexual Maturation / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D013256:Steroids / Q000096:biosynthesis
chemical_list: D056742:Cyclin D2; D006062:Gonadotropins; D011974:Receptors, LH; D013256:Steroids; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D001141:Aromatase