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 a lpha-hydroxy-5 alpha-pregnan-20-one, two major extrahepatic metabolite s of progesterone, had only minor effects or none at all. The myometri al 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 thes e steroids, either prior to or during labor. In the present investigat ion we Studied whether progesterone and the two named progesterone met abolites 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 proge sterone, 5 alpha-pregnane-3,20-dione, or 3 alpha-hydroxy-5 alpha-pregn an-20-one. The strips were then bisected; one half was superfused with progestin buffer, and the other half with plain buffer to serve for c ontrol purposes. In strips continuously exposed to progesterone, the o nset of contractions was delayed, compared with their progesterone-dep leted controls. This was as expected, according to current opinion reg arding progesterone and parturition. Once muscular contractions were e stablished, the contraction frequency was significantly higher, due to a shorter muscular relaxation time, in the progesterone-superfused st rips than in the controls and strips treated with progesterone metabol ite superfusion. This was unexpected and can be interpreted as if cont inuous presence of progesterone facilitates human myometrial contracti on frequency once contractions have started. Conversely, the 5 alpha-p rogesterone metabolites showed no effect or minor effects.