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V D Castracane

Publications and source records attributed to V D Castracane.

At least 91 records · Page 5Linked to original sources

Pharmacologic induction of luteolysis in cynomolgus monkeys (Macaca fascicularis).

Earlier studies reported from this laboratory demonstrated the luteolytic effect of a 5-day sequential regimen of 3 days of estrogen overlapped with 3 days of PGF2 alpha administered during the midluteal phase to cynomolgus monkeys. In this study, a different regimen, containing estrogen, lower doses of PGF2 alpha, and methylergonovine maleate (MEM), was used. Individual components of this modified sequential regimen were not effective as luteolytic agents. When 3 days of estrogen (40 micrograms of depoestradiol cypionate [DEC] on the first day and 40 micrograms of estradiol benzoate [EB] on second and third day) was followed by 3 days of MEM (400 micrograms, twice daily) overlapping 1 day of estrogen treatment, there was a significant shortening of the length of the menstrual cycle (less than 26 days) in eight of 10 animals, with a concomitant decline in plasma levels of progesterone. When a low dose of MEM (100 micrograms, twice daily), which was completely ineffective in shortening cycle lengths with the same estrogen treatment, was administered alternately with PGF2 alpha (5 mg twice daily, 11 of 14 animals had shortened cycles, with an associated decline in levels of progesterone. PGF2 alpha and MEM without the estrogen pretreatment did not have a significant effect on cycle lengths or blood levels of progesterone, thus demonstrating a synergism between estrogen and the other compounds in inducing luteolysis. Since the agents used in these sequential regimens have potent effects on the uterus, the treatments were repeated in hysterectomized monkeys to determine whether the uterus was involved in the mediation of luteolysis. These treatments caused a significant drop in plasma levels of progesterone by the tenth day after the preovulatory estrogen peak, thus demonstrating that the uterus is not essential to the luteolytic action.

Animals↗

Synergism of estrogen and bromergocryptine in the induction of luteolysis in cynomolgus monkeys (Macaca fascicularis).

Sequential administration of estrogen (40 microgram depoestradiol cypionate and estradiol benzoate) on cycle days 18--20 and bromergocryptine (CB-154; 0.5 mg/kg, twice daily) on cycle days 20-22 induced luteolysis in seven of nine cynomolgus monkeys, significantly shortened menstrual cycles (23.5 +/- 0.7 days), and caused a significant decline in plasma progesterone levels during the period of CB-154 administration. Two treated monkeys did not have shortened menstrual cycles, although a luteolytic effect on plasma progesterone was evident. One monkey with a late ovulation (confirmed by endocrine parameters and laparoscopic observation) was treated with the same regimen in the early luteal phase; this also resulted in a decline in plasma progesterone and a shortened luteal phase (11 days). Treatment with the estrogen or the CB-154 component alone had no effect on menstrual cycle length or plasma progesterone levels. Similarly, treatment with CB-154 throughout the luteal phase had no effect on luteal function. An abbreviated treatment consisting of 1 day of estrogen and 1 day of CB-154 administration gave some indication of a luteolytic effect. None of these treatments produced detectable side effects. These studies have demonstrated a synergism of estrogen and CB-154 in the induction of luteolysis in cynomolgus monkeys. The present regimen, because of the effectiveness and apparent lack of side effects, deserves further investigation for possible clinical application.

Animals↗

The attenuation of prostaglandin-induced luteolysis in decidual tissue-bearing pseudopregnant rats.

Decidual tissue (DT)-bearing pseudopregnancy (PSP) rats, in contrast to hysterectomized PSP rats, were resistant to a luteolytic regimen of either PGF2alpha or PGE2 when examined for the duration of PSP diestrus. The PG treatments, however, caused a marked fall in the serum progesterone levels on days 10 and 12, although the levels in DT-bearing rats on day 10 were significantly higher than in the hysterectomized rats.

Animals↗

Proestrous levels of LH and FSH subsequent to adrenalectomy the same morning.

Adrenalectomies and sham-adrenalectomies were performed on the day of proestrus between 0900 and 1000 hours. On the afternoon and evening of the same day, these animals, as well as unoperated control animals, were sacrificed at 2-hour intervals from 1400 through 2400 hours and blood was taken from the abdominal aorta. Plasma concentrations of LH and FSH were determined by radioimmunoassay. Adrenalectomized, sham-adrenalectomized, and normal rats all show a peak in LH levels at 1800 hours on proestrus. Peak concentrations of FSH were found at 2200 hours in control and adrenalectomized rats, while in the sham-adrenalectomized animals an advancement of the FSH surge by 2 hours, to 2000 hours, was seen.

Adrenalectomy↗

Considerations into the mechanism of estrogen-stimulated uterine prostaglandin synthesis.

Progesterone priming of the ovariectomized rat, followed by a single injection of estradiol-17beta (10 mug) is followed by an increased uterine synthesis of both PGF and PGE. The administration of an estrogen antagonist (MER-25; 10 mg) concomitantly with estradiol had no effect on uterine prostaglandin synthesis. Similarly, the administration of either Actinomycin D or cycloheximide, antibiotics demonstrated to inhibit mRNA and protein synthesis, respectively, is without effect on estrogen-stimulated uterine prostaglandin synthesis. These results are considered with regard to the classic receptor theory of estrogen action and are a preliminary indication that estrogen-stimulated uterine prostaglandin synthesis may not require those receptor mediated events.

Animals↗

The effect of reported prostaglandin synthetase inhibitors on estradiol-stimulated uterine prostaglandin biosynthesis in vivo in the ovariectomized rat.

Aspirin, indomethacin and naproxen have been shown to inhibit the release of prostaglandins E and F (PGE and PGF) from the estradiol-stimulated uterus of progesterone-pretreated ovariectomized rats. Under the present experimental conditions indomethacin (1 mg/rat) was found to be a potent inhibitor of PGF and E biosynthesis, but the duration of action was less than 24 hours, after which a rebound above control levles was observed.The compounds were without effect on estradiol-stimulated increases in uterine wet weight. delta'THC did not inhibit estradiol-stimulated PG biosynthesis but produced a significant rise (P less than 0.01) in PGE levels in uterine venous blood. A hypothesis is suggested to explain some of the pharmacological effects of delta'THC.

Animals↗

Effect of decidual tissue on the uterine production of prostaglandins in pseudopregnant rats.

The concentration of prostaglandin F (PGF) in uterine vein plasma of non-traumatized pseudopregnant rats and pseudopregnant rats with deciduomata were not significantly different from each other at any of the times of pseudopregnancy studied (Days 7, 10 and 12). There was a significant increase in PGF levels on Day 10 in both groups of pseudopregnant animals (P less than 0-05) compared to the Day 4 values, and PGE values were significantly greater on Day 10 in the decidual tissue-bearing rats (P less than 0-01). A slight but not significant elevation in PGE concentration was observed on Days 7 and 12 in rats with deciduomata, but there was no significant difference in the control rats on Days 4, 7, 10 or 12. The results indicate that the prolongation of pseudopregnancy in rats with deciduomata is not due to a decreased production of uterine PGs and lend support to the recent suggestion of a luteotrophic effect of decidual tissue in the rat.

Animals↗

Ovarian dehydrogenase activities: suggested adrenal involvement in luteolysis.

Immature rat ovarian dehydrogenase activity was studied during corpus luteum regression following withdrawal of prior pregnant mare serum gonadotrophin. Glucose-6-phosphate dehydrogenase activity declined to nontreatment levels whereas 6-phosphogluconate, malate, and isocitrate dehydrogenase dehydrogenases exhibited a partial return to normal. Adrenalectomy prior to PMS withdrawal enhanced the decline in MAD while sharply elevating G6PD and 20alpha-hydroxysteroid dehydrogenase. Corticosterone and progesterone prevented the G6PD changes induced by adrenalectomy and moderated the rise in 20alpha-OHSD. Adrenalectomy appears to enhance the process of luteolysis.

Adrenalectomy↗

The effect of inhibition of prostaglandin synthesis on ovarian hypertrophy in the rat.

Aspirin and indomethacin, inhibitors of prostaglandin biosynthesis, were utilized to determine the role of prostaglandins (PGs) in ovarian weight gain in rats following unilateral ovariectomy or treatment with PMSG. After unilateral ovariectomy, the compensatory ovarian hypertrophy was 185-0% compared with 139-8% and 97-5% in rats treated with indomethacin and aspirin, respectively. The adrenal weights in rats treated with aspirin were also reduced significantly. Administration of PGE2 or PGF2alpha with aspirin reversed the effect of aspirin on the adrenals but had no effect on the ovarian weight. Indomethacin and aspirin treatment of animals injected with PMSG also reduced the ovarian weight gain. If 100 mug PGE2 were given twice daily, this effect was reversed in both groups but thrice daily administration had no effect on rats receiving aspirin. In PMSG-treated rats, 100 mug PGF2alpha twice daily did not reverse the effect of indomethacin and aspirin, and actually enhanced the effect of aspirin.

Adrenal Glands↗