title: Reproductive functions of corticotropin-releasing hormone. Research and potential clinical utility of antalarmins (CRH receptor type 1 antagonists).
abstract: BACKGROUND
  The hypothalamic-pituitary-adrenal (HPA) axis exerts a complex, mostly inhibitory, effect on the female reproductive system. In addition, the principal regulator of this axis, the hypothalamic neuropeptide corticotropin-releasing hormone (CRH) and its receptors have been identified in most female reproductive tissues, including the ovary, uterus, and placenta. Furthermore, CRH is secreted in peripheral inflammatory sites where it exerts strong inflammatory actions. Antalarmins (CRH receptor type 1 antagonists) have been used to elucidate the roles of CRH in stress, inflammation and reproduction.
  
  
  METHODS
  We review existing data on the effects of CRH in the female reproductive system.
  
  
  RESULTS
  Ovarian CRH participates in female sex steroid production, follicular maturation, ovulation and luteolysis. Uterine CRH participates in decidualization, implantation, and early maternal tolerance. Placental CRH participates in the physiology of pregnancy and the onset of parturition. Circulating placental CRH is secreted mostly during the latter half of pregnancy and is responsible for the concurrently increasing physiologic hypercortisolism of this period. After labor and delivery, this hypercortisolism is ensued by a transient suppression of hypothalamic CRH secretion, which may explain the postpartum blues and depression and the increased autoimmune manifestations depression of period, the postpartum period.
  
  
  CONCLUSIONS
  These data show that CRH is present in female reproductive tissues, and is regulating key reproductive functions with an inflammatory component, such as ovulation, luteolysis, implantation, and parturition.
authors.affiliation: Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Ioannina, School of Medicine, Ioannina, Greece.
authors.forename: Sophia N
authors.initials: SN
authors.lastname: Kalantaridou
authors.forename: Antonis
authors.initials: A
authors.lastname: Makrigiannakis
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Zoumakis
authors.forename: George P
authors.initials: GP
authors.lastname: Chrousos
mesh_terms: D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000502:physiology*; D010064:Embryo Implantation / Q000187:drug effects / Q000502:physiology; D004967:Estrogens / Q000502:physiology; D053222:Fas Ligand Protein; D005260:Female; D005938:Glucocorticoids / Q000502:physiology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D036801:Parturition / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000502:physiology; D010920:Placenta / Q000502:physiology; D011247:Pregnancy; D011743:Pyrimidines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D012098:Reproduction / Q000187:drug effects / Q000502:physiology*; D019014:fas Receptor / Q000502:physiology
chemical_list: D004967:Estrogens; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; C505662:Faslg protein, rat; D005938:Glucocorticoids; D008562:Membrane Glycoproteins; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; C103016:antalarmin; D019014:fas Receptor; D003346:Corticotropin-Releasing Hormone