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.

Effects of human chorionic gonadotropin and gonadotropin releasing hormone analogue on plasma steroid hormones and spawning performances in golden rabbitfish Siganus guttatus

“…The decrease of E 2 levels 12 hr post injection may be related to the control of the HPG axis in the reproductive cycle in fish. Once the oocyte proceeds into the final stages of maturation, the follicle produces maturation‐inducing steroid (MIS) instead of E 2 as a response to LH (Cowan et al, ; François et al, ). The steroidogenic pathway in vitellogenic ovarian follicles produce two maturation‐inducing hormones (MIHs), 17,20β‐dihydroxy‐4‐pregnen‐3‐one (17,20β‐P) and 17,20β,21‐trihydroxy‐4‐pregnen‐3‐one (20β‐S).…”

“…The HPG axis produces substances that influence each other. These organs play significant roles in regulating gonadal maturation, ovulation and spawning, leading to successful reproduction (François et al, 2017;Zohar et al, 2010). Therefore, FSH, LH, and sex steroid hormones control gamete production in teleost species (Ohta, Mine, Yamaguchi, & Matsuyama, 2001;Yaron et al, 2003).…”

“…Additionally, the hormone pathway mechanisms differ between sexes which could result in different feedback rates. Both exogenous hormones, hCG and D-Ala 6 , Pro 9 -Net-mGnRH were found to significantly elevated ovar- François et al, 2017). The steroidogenic pathway in vitellogenic ovarian follicles produce two maturation-inducing hormones (MIHs), 17,20β-dihydroxy-4-pregnen-3-one (17,20β-P) and 17,20β,21-trihydroxy-4-pregnen-3-one (20β-S).…”

“…It is well documented that endocrine regulation of gonadal development provides valuable information on reproductive characteristics of fishes (Nagahama, ). The hypothalamic‐pituitary‐gonadal axis (HPG axis) of fish controls reproduction, gonadal development, sex steroid hormone secretion, maturation and spawning (Cowan, Azpeleta, & López‐Olmeda, ; François et al, ; Hou et al, ; Nagahama, ; Weltzien, Andersson, Andersen, Shalchian‐Tabrizi, & Norberg, ). Gonadotropins such as follicle‐stimulating hormone (FSH) and luteinizing hormones (LH) regulate the biosynthesis of sex steroids that subsequently control the processes of sexual behavior and spermation/ovulation (Nagahama & Yamashita, ; Schulz et al, ; Zohar, Munoz‐Cueto, Elizur, & Kah, ).…”

Seasonal changes in hepatosomatic index, gonadosomatic index and plasma estradiol‐17β level in captively reared female rabbit fish ( Siganus guttatus )

“…The hypothalamic‐pituitary‐gonad axis (HPG axis) controls reproduction, ovarian development, maturation, ovulation and spawning (François et al, ; Guiguen, Jalabert, Thouard, & Fostier, ; Levavi‐Sivan, Bogerd, Mañanós, Gómez, & Lareyre, ; Mylonas, Fostier, & Zanuy, ), but obviously the role of liver in this process is important as well (Arukwe & Goksoyr, ; Nunes, Silva, & Soares, ). The role of the liver during reproductive cycle is well known, especially during vitellogenesis (Cowan, Azpeleta, & López‐Olmeda, ) and the seasonal changes in liver weight during reproductive cycle could be related to vitellogenesis (Hismayasari, Marhendra, Rahayu, Saidin, & Supriyadi, ).…”