Mathematical modeling of gonadotropin-releasing hormone signaling

•We describe a mechanistic model for GnRH action via its Gq/11-coupled receptors.•GnRH is secreted is pulses which can increase signaling efficiency and robustness.•Maximal responses occur at sub-maximal GnRH pulse frequency.•This may reflect incoherent feedforward loops but not upstream negative feedback.•Single cell measures reveal noisy signaling systems with marked information loss.

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.