Mathematical modeling of gonadotropin-releasing hormone signaling

Amitesh Pratap,Kathryn L Garner,Margaritis Voliotis,Krasimira Tsaneva-Atanasova,Craig A Mcardle

doi:10.1016/j.mce.2016.08.022

Abstract

Gonadotropin-releasing hormone (GnRH) acts via G-protein coupled receptors on pituitary gonadotropes to control reproduction. These are Gq-coupled receptors that mediate acute effects of GnRH on the exocytotic secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as the chronic regulation of their synthesis. GnRH is secreted in short pulses and GnRH effects on its target cells are dependent upon the dynamics of these pulses. Here we overview GnRH receptors and their signaling network, placing emphasis on pulsatile signaling, and how mechanistic mathematical models and an information theoretic approach have helped further this field.

Highlights

Gonadotropin-releasing hormone (GnRH) acts via G-protein coupled receptors on pituitary gonadotropes to control reproduction
GnRH influences the expression of many genes(Yuen et al, 2002, 2009; Ruf et al, 2006), most work in this area focuses on transcription of the gonadotrope signature genes for a-gonadotropin subunit (aGSU), LHb, FSHb and GnRHR, all of which are increased by
We have focused our attention on a simplified network encompassing the remarkably small group of chemicals acting on or within gonadotrophs that have been shown by knock-down or inactivating mutation to be essential for reproduction and have added Ca2þ to this list in light of the wealth of evidence showing its requirement for hormone secretion (Fig. 1A)

Summary

GnRH signaling: an overview

GnRH is a hypothalamic decapeptide that mediates central control of reproduction It acts via receptors (GnRHR) on pituitary gonadotropes to control synthesis and secretion of the two gonadotropin hormones (LH and FSH) that in turn regulate gametogenesis and steroidogenesis in the gonads. All of the cloned mammalian GnRHR are in groups I or II, and the type I GnRHR of humans, rats, mice, pigs, sheep, and horses share >80%. Several Ca2þ-regulated proteins are known to mediate transcriptional effects of GnRH These include calmodulin (CaM), calmodulin-dependent protein kinases, the calmodulin dependent phosphatase calcineurin (Cn) and the Ca2þ dependent transcription factor NFAT (McArdle and Roberson, 2015)

GnRH: a dynamic peptide

GnRHR: a short tail

GnRH signaling: a mechanistic modeling approach

GnRH signaling: an information theoretic approach

Summary