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The Human Myometrium as a Target for Melatonin

Institute for Hormone and Fertility Research, University of Hamburg (N.S.-L., N.H., D.M., J.O.), and Institute of Anatomy, University of Hamburg Medical School (R.M.), 22529 Hamburg, Germany

Address all correspondence and requests for reprints to: Dr. James Olcese, Institute for Hormone and Fertility Research, University of Hamburg, Grandweg 64, 22529 Hamburg, Germany. E-mail: olcese{at}ihf.de.

The circadian timing of spontaneous human deliveries results in births occurring statistically more often during the nocturnal phase of the 24-h cycle. The neuroendocrine mechanisms underlying this physiological phenomenon are not understood. In an effort to test the hypothesis that melatonin may serve as an endocrine signal for coordinating myometrial events in the human, we determined the mRNA expression of both MT1 and MT2 melatonin receptor isoforms in pregnant as well as nonpregnant myometrial biopsies by means of RT-PCR and in situ hybridization histochemistry. Additionally, we could demonstrate specific, high affinity iodomelatonin binding to myometrial tissues of both pregnant and nonpregnant women. Primary cultures of myocytes responded differentially from melatonin in terms of cAMP signaling depending on the reproductive state. These results imply that melatonin may have the potential to modulate myometrial function in the human, a finding that could open up new possibilities for the development of novel therapeutic agents.

This work was supported by a grant from the Leidenberger Forschung GmbH. A portion of these findings were submitted in fulfillment of the M.D. degree by N.H.

Present address for N.S.-L.: Department of Experimental Gynecology, Clinic of Obstetrics and Gynecology, University of Hamburg Medical School, 22529 Hamburg, Germany.

Abbreviations: GTPS, Guanosine 5'-O-3-thiophosphate; NP, nonpregnant; P, pregnant; 4P-PDOT, 4-phenyl-2-propionamidotetralin.

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