GnRH pulse frequency-dependent differential regulation of LH and FSH gene expression

Abstract

The pituitary gonadotropin hormones, FSH and LH, are essential for fertility. Containing an identical α-subunit (CGA), they are comprised of unique β-subunits, FSHβ and LHβ, respectively. These two hormones are regulated by the hypothalamic decapeptide, GnRH, which is released in a pulsatile manner from GnRH neurons located in the hypothalamus. Varying frequencies of pulsatile GnRH stimulate distinct signaling pathways and transcriptional machinery after binding to the receptor, GnRHR, on the cell surface of anterior pituitary gonadotropes. This ligand-receptor binding and activation orchestrates the synthesis and release of FSH and LH, in synergy with other effectors of gonadotropin production, such as activin, inhibin and steroids. Current research efforts aim to discover the mechanisms responsible for the decoding of the GnRH pulse signal by the gonadotrope. Modulating the response to GnRH has the potential to lead to new therapies for patients with altered gonadotropin secretion, such as those with hypothalamic amenorrhea or polycystic ovarian syndrome.

Keywords: FSH; GnRH; Gonadotrope; Gonadotropins; LH.

FIG. 1

Model for the regulation of Fshb and Lhb transcription by pulsatile GnRH. Fast and slow frequency pulsatile GnRH stimulates signaling cascades that mediate the activity and synthesis of transcription factors controlling gonadotropin subunit gene transcription. The pathways stimulated by GnRH can vary in magnitude and duration (as indicated by weighted arrows) in a manner dependent on pulse frequency and lead to the induction of distinct transcription factor networks.