Progesterone withdrawal without parturition

doi:10.1016/0028-2243(83)90293-9

European Journal of Obstetrics & Gynecology and Reproductive Biology

Volume 15, Issue 1, April 1983, Pages 25-30

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Abstract

It has been demonstrated that administration of 100 mg of trilostane (an inhibitor of 3β-hydroxy-steroid dehydrogenase) to late pregnant sheep will rapidly lower circulating levels of progesterone and that delivery ensues. Our intention was to reduce the dose of trilostane in order to separate the latter two sequelae and thereby obtain insight into the relationship between progesterone and prostaglandin biosynthesis. At the dose chosen (10 mg) the treatment did not induce parturition in 4 chronically catheterized sheep during late pregnancy. Circulating progesterone concentrations declined precipitously in all ewes but recovered to near basal values by 24 h after administration of trilostane. Circulating concentrations of 13,14-dihydro-15-keto-prostaglandin F_2α rose slightly but significantly at 4–5 h after administration of trilostane but never reached values normally associated with labor. Plasma estradiol levels were unchanged by treatment. These results are consistent with the view that progesterone withdrawal must be of a critical magnitude and duration for prostaglandin biosynthesis to be sufficiently stimulated to induce labor in sheep during late gestation.

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Cited by (1)

Inhibition and augmentation of progesterone production during pregnancy: Effects on parturition in rhesus monkeys
1997, American Journal of Obstetrics and Gynecology
OBJECTIVES: Uterine quiescence during mammalian pregnancy is attributed to progesterone. However. systemic progesterone levels remain elevated in primates before parturition. Epostane, a selective 3β-hydroxysteroid dehydrogenase inhibitor, and progesterone (with or without epostane) were administered to late pregnant rhesus monkeys to clarify the role of progesterone in primate parturition.
STUDY DESIGN: On days 122 to 132 of gestation (term 167 days), 11 rhesus monkeys (Macaca mulatta) with timed pregnancies were divided into three treatment groups: (1) epostane alone (10 mg/kg subcutaneously), (2) epostane with progesterone subcutaneously in Silastic silicone rubber capsules, and (3) progesterone implants only with no surgical instrumentation. Maternal and fetal blood and amniotic fluid were sampled for progesterone, estrone, estradiol, cortisol, testosterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and amniotic fluid was sampled for prostaglandins E₂ and F_2α. Uterine activity was monitored continuously by electromyography and intraamniotic pressure. Cervical status was assessed by a modified Bishop's score. Production of prostaglandins E₂ and F_2α by amnion was determined by tissue superfusion. The group of three noninstrumented monkeys, which received only progesterone Silastic silicone rubber implants subcutaneously at 146 to 148 days, were observed until spontaneous vaginal delivery.
RESULTS: Epostane reduced maternal and fetal progesterone levels by 75% and 50%, respectively, followed by increased uterine activity and cervical ripening within 24 hours and vaginal delivery within 48 hours. Amniotic fluid progesterone decreased to undetectable levels. Progesterone implants prevented the epostane-induced decrease in maternal and fetal progesterone levels and the associated myometrial and cervical changes until the implants were removed. Alterations in other steroid hormones were consistent with inhibition of 3β-hydroxysteroid dehydrogenase. Amniotic prostaglandin E₂ production was increased sixfold by epostane (p < 0.05) but did not reach the high levels normally seen at spontaneous parturition. Animals that received progesterone implants alone had markedly elevated circulating progesterone concentrations yet were delivered spontaneously at term (range 163 to 167 days).
CONCLUSIONS: Progesterone withdrawal induces preterm labor and delivery (which can be blocked by progesterone substitution) but exogenous progesterone, even in substantial quantities, does not prevent parturition at term. (Am J Obstet Gynecol 1997;176:682-91.)

^∗: Present address: Cecil H. and Ida Green Center for Reproductive Biology Sciences, Departments of Obstetrics and Gynecology and Biochemistry, The University of Texas, Southwestern Medical School, 5323 Harry Hines Boulevard, Dallas, TX 75235, U.S.A.

^∗∗: Present address: ARC Animal Breeding Research Organisation, West Mains Road, Edinburgh EH9 3JQ, U.K.

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Progesterone withdrawal without parturition

Abstract

Prostaglandins

Prostaglandins

Prostaglandins

Prostaglandins

Prostaglandins

Endocrine changes associated with luteal regression in the ewe; the secretion of ovarian oestradiol, progesterone and androstenedione and prostaglandin F2α throughout the oestrous cycle

J. Endocr.

Respiratory movements and rapid eye movement sleep in the foetal lamb

J. Physiol.

Radioimmunoassay of estradiol-17β without chromatography

J. clin. Endocr.

Control of utero-ovarian venous prostaglandin F: acute effects of vaginal and cervical stimulation

J. Endocr.

Endocrine changes associated with luteal regression in the ewe; the secretion of ovarian oestradiol, progesterone and androstenedione and prostaglandin F_2α throughout the oestrous cycle