Matrix metalloproteinases in reproductive endocrinology

One of the most common mechanisms for transactivation of epidermal growth factor receptor (EGF-R) by G protein-coupled receptors (GPCRs) is through the release of local EGF-like ligands from transmembrane precursors by the proteolytic action of matrix metalloproteinases (MMPs). These enzymes are crucial factors in the normal physiology of the reproductive system and also participate in neuroendocrine regulation through mediation of gonadotropin-releasing hormone (GnRH) action. Recent studies by Roelle et al. showed that GnRH-induced activation of the EGF-R and extracellular signal-regulated kinases 1 and 2 (ERK1/2) in pituitary gonadotrophs occurs through ectodomain shedding of heparin binding-EGF (HB-EGF) by MMP2 and MMP9, indicating a crucial role for MMPs in GnRH signalling.