Gonadotropin regulation by pulsatile GnRH: Signaling and gene expression

The precise orchestration of hormonal regulation at all levels of the hypothalamic-pituitary-gonadal axis is essential for normal reproductive function and fertility. The pulsatile secretion of hypothalamic gonadotropin-releasing hormone (GnRH) stimulates the synthesis and release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by pituitary gonadotropes. GnRH acts by binding to its high affinity seven-transmembrane receptor (GnRHR) on the cell surface of anterior pituitary gonadotropes. Different signaling cascades and transcriptional mechanisms are activated, depending on the variation in GnRH pulse frequency, to stimulate the synthesis and release of FSH and LH. While changes in GnRH pulse frequency may explain some of the differential regulation of FSH and LH, other factors, such as activin, inhibin and sex steroids, also contribute to gonadotropin production. In this review, we focus on the transcriptional regulation of the gonadotropin subunit genes and the signaling pathways activated by pulsatile GnRH.