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The Journal of Clinical Endocrinology & Metabolism Vol. 83, No. 11 4107-4115
Copyright © 1998 by The Endocrine Society

Original Studies

Corticotropin-Releasing Hormone Receptor Subtype 1 Is Significantly Up-Regulated at the Time of Labor in the Human Myometrium1

M. Yvette Stevens, John R. G. Challis and Stephen J. Lye

Medical Research Council Group in Fetal and Neonatal Health and Development (M.Y.S., J.R.G.C.); Medical Research Council Group in Development and Fetal Health (S.J.L.); the Departments of Physiology and Obstetrics and Gynecology, University of Toronto; and the Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5S 1A8

Address all correspondence and requests for reprints to: Dr. J. R. G. Challis, Department of Physiology, University of Toronto, Medical Sciences Building, Room 3205/7, 1 Kings College Circle, Toronto, Ontario, Canada M5S 1A8. E-mail j.challis{at}utoronto.ca

Circulating concentrations of CRH rise late in human pregnancy, reaching a peak at labor. The presence of functional CRH receptors, CRH-R1 and CRH-R2, in the human myometrium suggests that CRH may modulate uterine activity. We hypothesized that the number of CRH receptors would be higher in myometrium than fetal membranes (FM) and would change during labor.

Myometrial samples were collected from the lower segment (LS) in nonpregnant, preterm (32 ± 2 weeks), and term (39 ± 1.6 weeks) pregnant patients before and at labor. Fundus and LS samples were also collected from nonpregnant, pregnant, laboring, and postpartum women. FM were collected at term and at labor. We identified CRH receptors in myometrium and FM by semiquantitative RT-PCR and immunohistochemistry.

CRH-R1 messenger ribonucleic acid (mRNA) in the LS was decreased in pregnancy and increased significantly in both preterm and term labor (P < 0.05), but remained unchanged in the fundus. CRH-R2 mRNA was present in 28% of LS myometrium with no change at labor. CRH-R1 and CRH-R2 protein was localized to myometrial smooth muscle in nonpregnant and laboring patients, with lower levels at term. CRH-R1 mRNA was present in chorion and decidua, but CRH-R2 was undetectable in these tissues. We conclude that CRH-R1 is expressed preferentially in myometrium and FM. Changes in CRH receptors during labor are consistent with CRH mediating effects on myometrial activity.




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