Influence of 5alpha- and 5beta-reduced progestins on the contractility of isolated human myometrium at term.
It is very well known that progesterone induces uterine relaxation on myometrium contractile activity. However, little attention has been paid to the effect induced by its metabolites on human uterine contractility. Therefore, we set out to analyze the potential relaxing effect of some 5alpha- and 5beta-reduced progesterone derivatives on the spontaneous contractility of myometrium from pregnant women. Samples were obtained by caesarian section at 38-40 weeks of pregnancy. Spontaneous uterine contractions were recorded in vitro in the presence of progesterone, or progestins independently, at different non-cumulative microM concentrations. The progestins elicited an immediate relaxing effect that was concentration-dependent. With the exception of two 5alpha-reduced progestins (5alpha and 3beta,5alpha), the remaining progestins used in the present study were more potent than progesterone. The potency order with respect to their IC50 values was: 3alpha,5alpha (35 microM) > 5beta (81 microM) > 3beta,5beta (156 microM) > 3alpha,5beta (205 microM) > P4 (225 microM) > 5alpha (19 mM) > 3beta,5alpha (28 mM). When tissues were washed, the contractile activity was recovered. This rapid and reversible relaxing effect was not blocking by antiprogestin RU 486, suggesting that is not through receptor-mediated genomic action. The metabolites from progesterone may also determine the pattern of motility, ensuring the necessary quiescent environment to prevent abortion during gestation.
Perusquía
M
M
Department of Cell Biology, Biomedical Research Institute, National Autonomous University of Mexico, Mexico City. perusqui@servidor.unam.mx
Jasso-Kamel
J
J
D000328:Adult; D002585:Cesarean Section; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D015394:Molecular Structure; D009215:Myometrium / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D011277:Pregnanediones / Q000737:chemistry / Q000494:pharmacology*; D011282:Pregnenediones / Q000737:chemistry / Q000494:pharmacology*; D011374:Progesterone / Q000494:pharmacology; D011372:Progestins / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014590:Uterine Contraction / Q000187:drug effects* / Q000502:physiology
D011277:Pregnanediones; D011282:Pregnenediones; D011372:Progestins; D011374:Progesterone