Advances in the Regulation of Mammalian Follicle-Stimulating Hormone Secretion

Abstract

Mammalian reproduction is mainly driven and regulated by the hypothalamic-pituitary-gonadal (HPG) axis. Follicle-stimulating hormone (FSH), which is synthesized and secreted by the anterior pituitary gland, is a key regulator that ultimately affects animal fertility. As a dimeric glycoprotein hormone, the biological specificity of FSH is mainly determined by the β subunit. As research techniques are being continuously innovated, studies are exploring the underlying molecular mechanism regulating the secretion of mammalian FSH. This article will review the current knowledge on the molecular mechanisms and signaling pathways systematically regulating FSH synthesis and will present the latest hypothesis about the nuclear cross-talk among the various endocrine-induced pathways for transcriptional regulation of the FSH β subunit. This article will provide novel ideas and potential targets for the improved use of FSH in livestock breeding and therapeutic development.

Actions and Roles of FSH in Germinative Cells

“…FSH acts on follicular development and growth in females; a role is also played in in vitro models during the early stages of folliculogenesis [ 2 , 240 , 241 ]. However, the effects of FSH in culture may vary according to several factors, such as FSH source and concentration, species, and even culture system (reviewed by [ 213 ]).…”

“…Follicle stimulating hormone (FSH) and luteinizing hormone (LH) are gonadotropins essential for proper reproduction and fertility in both females and males; specifically, they are key players in germ cell formation [ 1 , 2 ]. In females, several essential oocyte formation processes are triggered by gonadotropins FSH and LH, mainly through the stimulation of granulosa cell proliferation, antrum formation in secondary ovarian follicles, growth and maturation of antral follicles, and estradiol production, resulting, together, in folliculogenesis, oogenesis, oocyte meiotic maturation, and oocyte competence [ 3 , 4 ].…”

“…Furthermore, through these cells, this hormone indirectly regulates spermatogonial stem cells (SSCs) and creates the adequate environment for germinative cells proliferation and differentiation [ 7 ]. Additionally, they regulate other physiological activities that have biological effects on the hypothalamus, pituitary, and reproductive organs [ 2 , 8 , 9 , 10 ].…”

“…In the past decade, FSH's actions in reproductive physiological or pathological conditions have been more precisely studied, in both males and females, using genetic analysis approaches. Interestingly, mutations in the FSHβ sequence have already been reported as a cause for infertility in males, whereas FSHβ polymorphisms in females seem to affect the basic level of FSH in different ways, affecting the ovarian activity, either due to a positive response to exogenous gonadotropin administration or to alterations of the phenotype in several disfunctions such as PCOS and premature ovarian failure, for example [2,4,43,44,[60][61][62][63][64][65][66].…”

An overview of FSH-FSHR biology and explaining the existing conundrums

“…Activin enhances biosynthesis and secretion whereas inhibin downregulates FSH synthesis. Regulation of FSH synthesis and secretion was recently reviewed [ 1 , 2 ]. It regulates the development, growth, pubertal maturation, and reproductive processes of the body.…”