“Reproductive” Corticotropin-Releasing Hormone NIKOLAOS VITORATOS, a DIMITRIOS C. PAPATHEODOROU, b SOPHIA N. KALANTARIDOU, c AND GEORGE MASTORAKOS d a Second Department of Obstetrics and Gynecology, Aretaieion Hospital, Medical School, University of Athens, Athens, Greece b Department of Obstetrics and Gynecology, Nikaia General Hospital, Athens, Greece c Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Ioannina Medical School, Ioannina, Greece d Endocrine Unit, Second Department of Obstetrics and Gynecology, Aretaieion Hospital, Medical School, University of Athens, Athens, Greece ABSTRACT: Corticotropin-releasing hormone (CRH), a 41 amino acid peptide, is an important regulatory molecule synthesized by neurons of the parvocellular and magnocellular hypothalamic paraventricular nu- clei. It acts as the major physiologic corticotropin (ACTH) secretagogue. The CRH gene is located in humans on chromosome 8. The CRH hor- mone family has at least four ligands, two receptors (CRH-R1 and CRH- R2), and a binding protein (CRHbp). CRH is the principal regulator of the hypothalamic-pituitary-adrenal axis. Furthermore, CRH has been identified in most female reproductive tissues including the uterus, the placenta, and the ovary. CRH produced in the endometrium may partic- ipate in decidualization, implantation, and early maternal tolerance to semiallograft embryo. Placental CRH may participate in the physiology of pregnancy, in late pregnancy complications such as preterm labor and preeclampsia, and also in the onset of parturition. Ovarian CRH is in- volved in follicular maturation, ovulation, and luteolysis. Increased levels of unbound placental CRH may be responsible for the hypercortisolism of the second half of pregnancy. This hypercortisolism is followed by a transient suppression of hypothalamic CRH secretion in the postpartum period. This may explain the depressive states frequently observed in the postpartum period. KEYWORDS: corticotropin-releasing hormone; CRH; hypothalamic par- aventricular nuclei; hypothalamic-pituitary-adrenal axis; HPA Address for correspondence: Dr. G. Mastorakos, 3 Neofytou Vamva Street, Athens, Greece, 10674. Voice: +30-6977698009; fax: +302103636229. e-mail: mastorak@mail.kapatel.gr Ann. N.Y. Acad. Sci. 1092: 310–318 (2006). C  2006 New York Academy of Sciences. doi: 10.1196/annals.1365.029 310