GnRH is synthesized as a large prohormone and released with gonadotrophin associated peptide (GAP). It acts on the gonadotroph via a G-protein (G) linked receptor that activates phospholipase C (PLC) that stimulates the inositol signaling pathway (see Box 1.10).

GnRH is secreted in a pulsatile manner with one pulse occurring approximately each hour.

Administration of long-acting agonist analogs induces an initial stimulation of LH (and FSH) but over a few days causes complete desensitization of the pituitary gonadotroph.

Loss of endogenous GnRH secretion induces loss of GnRH receptors and the LH response to a bolus injection of GnRH is very low.

Abbreviations: PIP₂, phosphatidylinositol 4, 5-bisphosphate; IP₃, inositol 1,4,5-trisphosphate; DAG, diacylglycerol; PKC, protein kinase C.