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Reproductive Functions of Corticotropin-Releasing Hormone. Research and Potential Clinical Utility of Antalarmins (CRH Receptor Type 1 Antagonists)

Authors

  • Sophia N Kalantaridou,

    1. Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Ioannina, School of Medicine, Ioannina, Greece
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  • Antonis Makrigiannakis,

    1. Department of Obstetrics and Gynecology, University of Crete, School of Medicine, Heraklion, Greece
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  • Emmanouil Zoumakis,

    1. Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA
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  • George P Chrousos

    1. Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA
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Address reprint requests to George P. Chrousos MD, Chief, Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Building 10, Room 9D42, Bethesda, Maryland 20892, USA.
E-mail: chrousog@mail.nih.gov

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.

Method of study:  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.

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