CORTISOL BLOCKADE OF PROGESTERONE - A POSSIBLE MOLECULAR MECHANISM INVOLVED IN THE INITIATION OF HUMAN LABOR

In most mammals, labor is heralded by progesterone withdrawal, which i s believed to be related to the activation of multiple pathways leadin g to parturition. In humans, despite no decrease in placental progeste rone production, activation of similar pathways preceding labor sugges ts the presence of an endogenous antiprogestin, which we reasoned migh t: be cortisol, whose secretion from the fetal adrenal rises markedly at the end of human gestation. We report that in primary cultures of h uman placenta, cortisol is able to compete with the action of progeste rone in the regulation of the corticotropin-releasing hormone (CRH) ge ne. CRH is a peptide highly expressed in human placenta at the end of gestation, which has been suggested to be involved in regulating the t iming of parturition. These findings provide a model for functional pr ogesterone withdrawal at the end of human pregnancy, which may be invo lved in the initiation of labor.