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.
Shah
Bukhtiar H
BH
Section on Hormonal Regulation, Endocrinology and Reproduction Research Branch/National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-4510, USA. shahb@mail.nih.gov
Catt
Kevin J
KJ
D066246:ErbB Receptors / Q000502:physiology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D012098:Reproduction / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology
D007987:Gonadotropin-Releasing Hormone; D066246:ErbB Receptors; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9