15-keto-13-14-dihydroprostaglandin-f2alpha and trilostane

The mechanism by which prostaglandin F2 alpha terminates luteal function in the sheep is unclear even though it is used extensively in animal husbandry. At the time of luteal regression, a decrease in 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity is apparent in the corpus luteum, but it is not known whether the decrease in enzyme activity is the primary cause of structural luteolysis. The effect of trilostane, a 3 beta-HSD inhibitor, on luteal function and morphology has therefore been investigated. Intravenous injection of trilostane in the mid-luteal phase of the oestrous cycle caused a decrease in ovarian tissue progesterone content. A transient decrease in peripheral and utero-ovarian vein plasma progesterone was observed but there was no significant effect on the length of the luteal phase of the cycle. There was no significant change in plasma 13,14-dihydro-15-oxo-prostaglandin F2 alpha during the period when plasma progesterone was depressed. Morphological examination of the corpora lutea revealed a decrease in the concentration of electron-dense granules without any other features of impending luteal regression. When plasma progesterone was reduced for more than 10 h by two injections of trilostane 4h apart, there was again no subsequent effect on the length of the oestrous cycle or on the return to oestrus. Plasma progesterone returned to preinjection levels within 24 h of injection. This evidence suggests that competitive inhibition of 3 beta-HSD activity, per se, is ineffective in bringing about structural luteolysis.

Topics: 3-Hydroxysteroid Dehydrogenases; Animals; Corpus Luteum; Cytoplasmic Granules; Dihydrotestosterone; Dinoprost; Estrus; Female; Pregnancy; Progesterone; Prostaglandins F; Sheep

Changes in the concentrations of progesterone, 17 beta-estradiol and 13, 14-dihydro-15-oxo-prostaglandin F2 alpha (PGFM) were evaluated in the peripheral plasma of rabbits during late pregnancy by treating trilostane, an inhibitor of 3 beta-hydroxysteroid dehydrogenase, in an attempt to obtain further insight into the involvement of progesterone and prostaglandin (PG) in the initiation of parturition. The concentrations of progesterone were 18.8 +/- 2.2 ng/ml (mean +/- SE, n = 6) before administration of the inhibitor, significantly (p less than 0.05) fell to 7.6 +/- 1.0 ng/ml (n = 6) at 30 min, and remained low until 10 h after the drug administration. The concentrations of progesterone were still low (5.4 +/- 0.5 ng/ml, n = 6) at 20-24 h after administration of the inhibitor, and were also low (4.9 +/- 2.2 ng/ml, n = 6) at delivery. Premature deliveries occurred at 28.8 +/- 2.0 h after injection of trilostane (on days 29 of gestation). Increased concentrations of PGFM were observed at delivery. However, administration of trilostane induced no discernible changes in the concentration of estradiol. These findings suggest that delivery is induced by progesterone withdrawal and that synthesis prostaglandin F2 alpha is remarkably increased at delivery in the rabbit.

Topics: 3-Hydroxysteroid Dehydrogenases; Animals; Dihydrotestosterone; Dinoprost; Estradiol; Female; Labor, Obstetric; Pregnancy; Progesterone; Prostaglandins F; Rabbits

It has been demonstrated that administration of 100 mg of trilostane (an inhibitor of 3 beta-hydroxysteroid 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 F2 alpha 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.

Topics: Animals; Dihydrotestosterone; Dinoprost; Estradiol; Female; Labor, Obstetric; Pregnancy; Progesterone; Prostaglandins F; Sheep

The concentration of progesterone in the peripheral plasma of seven sheep during late pregnancy was reduced by injection of an inhibitor of 3 beta-hydroxysteroid dehydrogenase activity. Concentrations of progesterone were 10.0 +/- 1.0 (S.E.M) ng/ml (n = 6) before injection of the inhibitor, fell to 1.39 +/- 0.40 ng/ml (n = 6) 30 min after injection, and remained within this lowered range for 6 h after injection. By 20-24h and 30-35h after injection progesterone concentrations had recovered to 4.63 +/- 0.94 and 14.07 +/-4.17 ng/ml respectively (n = 6). Six out of seven ewes delivered prematurely 32.5 +/- 2.9h after injection. Delivery appeared to be normal, and was associated with increasing concentrations of 13, 14-dihydro-15-oxo prostaglandin F2 alpha in peripheral plasma. Concentrations of oestradiol-17 beta in peripheral plasma were slightly raised immediately before delivery, at which time progesterone concentrations were within the preinjection range. These data suggest that progesterone withdrawal is one mechanism that initiates increased prostaglandin F2 alpha secretion in the pregnant sheep.

Topics: Abortifacient Agents; Abortifacient Agents, Steroidal; Animals; Dihydrotestosterone; Dinoprost; Female; Labor, Obstetric; Pregnancy; Progesterone; Prostaglandins F; Radioimmunoassay; Sheep