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BOR - Papers in Press, published online ahead of print March 9, 2005.
Biol Reprod 2005, 10.1095/biolreprod.104.036954
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BIOLOGY OF REPRODUCTION 73, 214–221 (2005)
DOI: 10.1095/biolreprod.104.036954
© 2005 by the Society for the Study of Reproduction, Inc.

Androgens Induce Relaxation of Contractile Activity in Pregnant Human Myometrium at Term: A Nongenomic Action on L-Type Calcium Channels1

Mercedes Perusquía 2 3, Erika Navarrete 3, Jaime Jasso-Kamel 3, and Luis M. Montaño 4,5 

Departamento de Biología Celular y Fisiología,3 Instituto de Investigaciones Biomédicas Departamento de Farmacología,4 Facultad de Medicina, Universidad Nacional Autónoma de México, 04510 México D.F., México Instituto Nacional de Enfermedades Respiratorias,5 14080 México D.F., México

It has long been accepted that progesterone regulates uterine contractile activity. However, little is known about the role of androgens in female physiology, and their importance and biological function on myometrial contractility so far have received limited attention. In this work, we examined the direct effect of androgens on the contractile activity of the isolated human myometrium. Myometrial biopsies were obtained, with consent, from pregnant women undergoing elective cesarean section at term. Each androgen tested (dehydroepiandrosterone, testosterone, 5{alpha}- and 5ß-dihydrotestosterone, androsterone, or androstanediol) caused a concentration-dependent inhibition of spontaneous contractile activity; a relaxing effect of these androgens was also observed on the contractions induced by high potassium (KCl) solution. Interestingly, nonpregnant myometrium was also sensitive to androgen-induced relaxation. 5ß-Dihydrotestosterone (5ß-DHT) was dramatically more potent than the other androgens in inducing myometrial relaxation in all preparations. Relaxation response to androgens had very rapid time courses and was affected by neither the specific antiandrogen (flutamide) nor inhibitors of protein synthesis (cycloheximide) and transcription (actinomycin D), implying that androgens act through a nongenomic mechanism. Importantly, 5ß-DHT significantly reduced the increase in intracellular calcium concentration associated with exposure to KCl in human myometrial smooth-muscle cells loaded with Fura-2-AM. The blockade of L-type calcium channels seems to be involved in the nongenomic relaxing action of androgens. These observations demonstrate that androgens may play a crucial role in maintaining pregnancy.

female reproductive tract, mechanisms of hormone action, pregnancy, steroid hormones, testosterone

1 Supported by the Dirección General de Apoyo al Personal Académico, Universidad Nacional Autónoma de México (PAPIIT; grant IN221102-2).

2 Correspondence: Mercedes Perusquía, Apartado Postal 70-492, CP 04511, México D.F., México. FAX: 5255 5622 3897; perusqui{at}servidor.unam.mx






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Copyright © 2005 by the Society for the Study of Reproduction.