Fluprostenol-induced softening of the cervix of the pregnant rat

Abstract

Fluprostenol, an analogue of prostaglandin F2 alpha, administered s.c. to rats on day 18 of pregnancy increased cervical creep, or softness, by the following day. Doses of fluprostenol 100-fold larger were necessary to increase uterine contractions. Fluprostenol produced falls in serum progesterone concentrations, increases in 20 alpha-dihydroprogesterone concentrations, no changes in oestradiol or relaxin concentrations and a reduction in the ovarian human chorionic gonadotrophin binding capacity in vitro. Fluprostenol was less potent in inducing cervical softness when administered per vaginam, and a dose which produced softening in pregnant rats was ineffective in ovariectomized steroid-maintained pregnant or pro-oestrous rats. The findings suggest that cervical softening by fluprostenol does not result from a simple direct action on the cervix or by increasing uterine contractions, but rather by an indirect hormonal action mediated by the ovaries. The results with the lowest dose of fluprostenol indicate that cervical softening could be produced without a sustained fall in serum progesterone concentrations. Fluprostenol is much more potent at increasing cervical softness in the pregnant rat than prostaglandin F2 alpha or prostaglandin E2. With fluprostenol the ratio of dose to induce uterine contractility relative to that to produce cervical softness was greater than with these natural prostaglandins, indicating the greater selectivity of fluprostenol in the pregnant rat.

Relaxin and progesterone secretion from aging corpora lutea and relaxin's action on the uterine cervix of the pig

“…The effects of RU 486 on cervical softening observed in clinical subjects and experimental animals probably result by antagonizing the actions of progesterone on the uterus and cervix, and/or reducing progesterone levels and thus convert the uterus and cervix from refractory organs to sensitive organs to respond to stimulatory actions of prostaglandins, oxytocin and relaxin. Cervical softening can be induced by the administration of prostaglandin E2 (PGEg), prostaglandin F2Q: (PGF2Û:), and their analogs to intact rats on day 18 (HoUingsworth et al, 1980;Williams et al, 1983). PGE2 acts directly on the cervix, whereas PGFga may pro moting cervical softening indirectly via its luteolytic effect on the ovaries to reduce progesterone production and secretion.…”