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

• The pituitary gonadotropin hormones, FSH and LH, are essential for fertility.
• GnRH regulates FSH and LH synthesis and secretion from gonadotropes.
• Preferential Fshb or Lhb subunit transcription is dependent on GnRH pulse frequency.
• Varying frequencies of pulsatile GnRH activate multiple distinct signaling pathways.
• Both stimulatory and repressive transcription factors are activated by pulsatile GnRH.

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.