Continuous progesterone exposure associated with high contraction frequency in human term myometrial strips

It has been shown that progesterone slightly reduced the work of human term myometrial strips. In vitro, 5 alpha-pregnane-3,20-dione and 3 alpha-hydroxy-5 alpha-pregnan-20-one, two major extra-hepatic metabolites of progesterone, had only minor effects or none at all. The myometrial strips were stored and superfused in a progestin-free buffer until the onset of contractions when progestin superfusion was commenced. In vivo, the human myometrium is never deprived of the influence of these steroids, either prior to or during labor. In the present investigation we studied whether progesterone and the two named progesterone metabolites would have a different effect when the myometrial strips were not deprived of steroid. Muscle biopsy samples from the lower uterine segment were immediately placed and stored in buffer containing progesterone, 5 alpha-pregnane-3,20-dione, or 3 alpha-hydroxy-5 alpha-pregnan-20-one. The strips were then bisected; one half was superfused with progestin buffer, and the other half with plain buffer to serve for control purposes. In strips continuously exposed to progesterone, the onset of contractions was delayed, compared with their progesterone-depleted controls. This was as expected, according to current opinion regarding progesterone and parturition. Once muscular contractions were established, the contraction frequency was significantly higher, due to a shorter muscular relaxation time, in the progesterone-superfused strips than in the controls and strips treated with progesterone metabolite superfusion. This was unexpected and can be interpreted as if continuous presence of progesterone facilitates human myometrial contraction frequency once contractions have started. Conversely, the 5 alpha-progesterone metabolites showed no effect or minor effects.