Mouse models for the analysis of gonadotropin secretion and action

Abstract

Gonadotropins are pituitary gonadotrope-derived glycoprotein hormones. They act by binding to G-protein coupled receptors on gonads. Gonadotropins play critical roles in reproduction by regulating both gametogenesis and steroidogenesis. Although biochemical and physiological studies provided a wealth of knowledge, gene manipulation techniques using novel mouse models gave new insights into gonadotropin synthesis, secretion and action. Both gain of function and loss of function mouse models for understanding gonadotropin action in a whole animal context have already been generated. Moreover, recent studies on gonadotropin actions in non-gonadal tissues challenged the central dogma of classical gonadotropin actions in gonads and revealed new signaling pathways in these non-gonadal tissues. In this Chapter, we have discussed our current understanding of gonadotropin synthesis, secretion and action using a variety of genetically engineered mouse models.

The Roles of Luteinizing Hormone, Follicle-Stimulating Hormone and Testosterone in Spermatogenesis and Folliculogenesis Revisited

“…In all, there is a consensus that there is an absolute requirement of T for spermatogenesis in most mammals, except for the photoperiod-dependent Djungarian hamster, whose spermatogenesis is FSH-dependent [ 52 ]. Several experimental approaches, including hypophysectomy, pharmacological Leydig cell ablation, inhibition of GnRH secretion or action by sex steroids and GnRH analogues, immunization against the hormone receptor or the contemporary approach utilizing knockout mouse models of LHR or LHB [ 47 , 48 , 53 , 54 , 55 ], and the GnRH-deficient hpg mouse model [ 56 , 57 , 58 ], have been utilized to abolish gonadotropin secretion and/or action, followed by selective replacement with LH/hCG or T. The targeted disruption of the Lhr gene for example, results in infertility, with the LH receptor KO (LuRKO) mice displaying highly elevated circulating LH, moderately elevated FSH, profoundly reduced circulating T and ITT, underdeveloped reproductive accessory glands, and arrested postnatal sexual development and infertility. The mice also have Leydig cell hypoplasia and the postmeiotic arrest of spermatogenesis [ 47 , 48 ].…”

Deletion ofGremlin-2alters estrous cyclicity and disrupts female fertility in mice

“…While the mean diestrous stage serum levels of estradiol and FSH were similar between wild type and Grem2 -/mice, the well-known correlation between estradiol and FSH was altered in Grem2 -/females. In wild type rodents, at metestrus and diestrus, low but rising levels of estradiol from granulosa cells of growing follicles negatively regulate production of FSH by suppressing hypothalamic secretion of gonadotropin hormone releasing hormone (53)(54)(55). Furthermore, circulating levels of inhibin suppress FSH production from the pituitary (55)(56)(57).…”

Analysis and Importance of FSH? Gene in Pig Reproductive Performance

“…The both pituitary gonadotropins, luteinizing hormone (LH) and the follicle-stimulating hormone (FSH), are complex heterodimer glycoproteins, composed of a common alpha (α) subunit and a speciesspecific beta (β) subunit (Sand et al 2013;Gagnon et al 2018). These subunits bind non-covalently to form a biologically active dimeric peptide hormone (Boime and Ben-Menahem 1999;Gilbert et al 2018).…”