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Corticotropin-Releasing Hormone and Proopiomelanocortin-Derived Peptides Are Present in Human Myometrium

Departments of Physiology and Obstetrics and Gynecology (V.L.C., T.G.T., S.J.L., J.R.G.C.), University of Toronto, Toronto, Ontario, Canada M5S 1A8; Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto, Ontario, Canada, M5G 1X5; and the Medical Research Council Group in Fetal and Neonatal Health and Development, the Medical Research Council Group in Development and Fetal Health, and the Department of Obstetrics and Gynecology (J.F.T., A.J.T., I.T.C.), University of Glasgow, Glasgow, Scotland G3 8SJ

Address all correspondence and requests for reprints to: Dr. John Challis, Department of Physiology, University of Toronto, 1 Kings College Circle, Toronto, Ontario, Canada M5S 1A8.

CRH and POMC-derived peptides are produced at a number of intrauterine sites in both the nonpregnant and pregnant states. It is hypothesized that CRH and POMC-derived peptides may be produced locally by the uterus to modulate myometrial contractility. This study has examined the distribution of these peptides in human uterine tissue during the ovulatory cycle and pregnancy. The immunoperoxidase staining method was used to localize CRH and POMC-derived peptides: ACTH, ß-endorphin, and MSH. Immunoreactive (IR-) CRH and IR-POMC-derived peptides, ß-endorphin and MSH, were observed in the myometrial smooth muscle, vascular smooth muscle, endometrial glandular epithelium, and luminal epithelium of the nonpregnant uterus (n = 17). Staining for IR-CRH did not change during the cycle from the proliferative (n = 8) to the secretory phases (n = 9). Conversely, staining for IR-ß-endorphin and IR-MSH was only observed during the secretory phase of the cycle (n = 9). In uterine tissue obtained from pregnant women (n = 20) IR-CRH was present in the myometrial smooth muscle, vascular smooth muscle, decidua, and glandular epithelium. IR-POMC-derived peptides were not detectable at any uterine site during pregnancy (n = 20). IR-CRH was measurable in myometrial extracts collected from pregnant women undergoing cesarean section (20.9 ± 3.8 ng/g wet wt; n = 7) and from nonpregnant premenopausal women undergoing hysterectomy (7.7 ± 2.1 ng/g wet wt; n = 6). IR-CRH concentrations significantly increased with pregnancy. Levels of messenger ribonucleic acid encoding for CRH were examined in nonpregnant (n = 4) and pregnant (n = 10) myometrial smooth muscle and were also significantly increased with pregnancy. This study has demonstrated that levels of CRH and POMC peptide in human uterine tissue change with pregnancy and that CRH is produced locally by myometrial smooth muscle cells. These studies are consistent with the possibility that the CRH peptide has an autocrine/paracrine activity during pregnancy and labor that may be related to the modulation of myometrial contractility.

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