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Biomedical subjects

R H Asch

Publications and source records attributed to R H Asch.

At least 163 records · Page 9Linked to original sources
PubMed1982

Luteolytic effect of azastene in the nonhuman primate.

The ability to block steroidogenesis with 4,4,17-alpha-trimethylandrost-5-eno[2,3,-d]isoxazol-17-ol (azastene) was studied in 3 different models. Oral administration of 500 mg to rhesus monkeys on different days of their luteal phase induced marked depression of circulating progesterone concentrations, and in some cases early onset of menses. Simultaneous administration of human chorionic gonadotropin (hCG) during the midluteal phase did not overcome the luteolytic effect of azastene. Concentrations of 50 micrograms/ml of azastene inhibited testosterone secretion by decapsulated mice testes in vitro in response to hCG [controls, 1165 +/- 196 ng/ml, azastene, 306 +/- 40 ng/ml (P less than .01)]. Production of progesterone by dispersed luteal cells from rhesus monkey corpora lutea was markedly inhibited by the presence of 25 and 50 micrograms/ml azastene in the incubation media (P less than .05 and less than .01, respectively). The availability of a compound that blocks in vivo and in vitro gonadal steroidogenesis opens a new approach to postcoital contraception in primates because of its luteolytic and interceptive activity. The possible mechanisms of action of azastene are discussed.

Abortifacient Agents↗
PubMed1981

The effects of an LH-RH antagonist ([N-Ac-D-Trp(1)(3), D-p-Cl-Phe(2), D-Phe(6), D-Ala(10)]-LH-RH) during the preovulatory period of the rhesus monkey.

Seven regularly cycling rhesus monkeys (Macaca mulatta) were used in this experiment. The animals were followed during two consecutive cycles. During the first cycle (control), the animals did not receive any treatment and the date of ovulation was determined by using daily total serum estrogens and serial laparoscopies. In the second cycle, the animals received 1 mg daily of [N-Ac-D-Trp(1)(3),D-p-Cl-Phe(2), D-Phe(6), D-Ala(10)-LH-RH by intramuscular injection from days 10-14. The date of ovulation was determined by using the same methodology as the control cycle. Blood samples were drawn daily from day 8 of the cycle until the onset of menses, and the serum was used to measure total estrogens, progesterone and LH. A significant delay of the preovulatory LH peak and ovulation occurred in 5 of the 7 animals resulting in a proportional increase in cycle length as compared to the control cycle. No changes in cycle length or date of LH peak occurred in the other 2 animals. One of them did not present signs of ovulation as determined by laparoscopy (no recognizable stigma or corpus luteum). Progesterone production and length of the luteal phase were not affected by the treatment.

Animals↗
PubMed1981

Human chorionic gonadotropin blocks the estrogen-induced luteinizing hormone release in long-term castrated rhesus monkeys: evidence for an ultrashort-loop negative feedback.

We studied the effects of human chorionic gonadotropin (hCG) administration on the biphasic response of luteinizing hormone (LH) to estrogen challenge in long-term castrated, female rhesus monkeys. Estradiol benzoate (EB), 400 micrograms, was administered to all animals at time zero; hCG, 2000 IU, was administered either concomitantly or 12 hours after EB. Blood samples were obtained every 6 hours for 58 hours, and then at 72 and 82 hours. Control animals received EB alone. Serum LH and beta hCG were determined by radioimmunoassay. Control animals showed a typical biphasic response to EB: an initial decrease in LH levels, 50% to 70% of baseline, from +6 hours until +30 hours; then a large increase, 150% to 190% of baseline, at +48 hours. Animals treated with hCG at time zero showed an initial decrease in LH, 40% to 70% of baseline, but LH returned to basal levels at +42 hours. Animals treated with hCG 12 hours after EB showed an initial decrease in LH, 45% to 55% of baseline, but LH returned to basal levels at +36 hours. These results suggest that an LH ultrashort-loop negative feedback may exist in the nonhuman primate.

Animals↗
PubMed1981

Fertility following fimbriectomy and tubo-ovarian microsurgery in the rabbit.

It is generally believed that tubal fimbriae function as a highly specialized and indispensable component of the ovum pickup mechanism. The present study was undertaken to examine the feasibility of creating a functional tubo-ovarian relationship following fimbriectomy. Fourteen New Zealand White rabbits underwent unilateral microsurgical fimbriectomy followed by creation of a distal ampullary flap which was oversewn to the exposed ovarian cortex. Two weeks after surgery, the animals were inseminated and induced to ovulate with an intravenous injection of 100 IU of human chorionic gonadotropin. Thirteen of fourteen uterine horns on the control side and ten of fourteen on the operated side became pregnant. The ratios of ova ovulated to those which implanted were 73.2% on the control side and 37.8% on the operated side. Morphologic studies revealed a normal complement of ciliated and secretory cells lining the endosalpinx of the juxtaposed ampullary flap. The portion of ovarian cortex covered by the flap similarly exhibited no morphologic abnormalities. These findings indicate that fertility can be maintained in the absence of fimbriae and suggest a surgical technique for restoration of fertility following elective sterilization by fimbriectomy or following pathologically induced destruction of the fimbriae.

Animals↗
PubMed1981

Inhibition of the postcastration rise of luteinizing hormone and follicle-stimulating hormone in female rhesus monkeys (Macaca mulatta) by the administration of a luteinizing hormone-releasing hormone inhibitory analog ([N-Ac-D-Trp1-3,D-p-Cl-phe2,D-Phe6,D-Ala10]-LH-RH).

Regularly cycling rhesus monkeys were bilaterally oophorectomized for study of postcastration rise of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The animals were divided in two groups, control animals, which received vehicle, and experimental animals, which received intramuscularly 1 mg of a potent luteinizing hormone-releasing hormone (LHRH) inhibitory analog ([N-Ac-D-Trp1-3,D-p-Cl-phe2,D-Phe6,D-Ala10]-LH-RH) from the day of castration for 10 days. The controls showed significant elevations of FSH and LH 3 to 4 days after castration, but in the experimental animals the rise in gonadotropins was blocked until the LHRH antagonist administration was discontinued. The dynamics of gonadotropin elevation after the discontinuation of [N-Ac-D-Trp1-3,D-p-Cl-phe2,D-Phe6,D-Ala10]-LH-RH administration were similar to those observed in control animals after castration. The availability of a compound that selectively inhibits FSH and LH secretion in primates opens a new approach to contraception and for the treatment of conditions in which gonadotropin inhibition is desired.

Animals↗
PubMed1981

Effects of delta 9-tetrahydrocannabinol during the follicular phase of the rhesus monkey (Macaca mulatta).

It is well documented in the literature that delta 9-tetrahydrocannabinol (THC) decreases serum concentrations of pituitary gonadotropins in several species. To study its effects in the menstrual cycle of regularly cycling rhesus monkeys, 2.5 mg/kg THC were administered to five animals from days 1-18 of the cycle [ovulation day in our colony, 15 +/- 1 day (mean +/- SD)]. Controls received vehicle (Tween 80 and saline) in an identical protocol. Animals were bled daily or every other day, and serum total estrogens, LH, PRL, and progesterone were determined by RIA. Serial laparoscopies were performed to visualize ovulation. Whereas animals treated with vehicle presented normal cycle lengths (26, 26, 29, 30, and 34 days), those treated with THC presented abnormal lengths (145, 76, 22, 94, and 59 days). All vehicle-treated cycles were ovulatory, while four of five THC cycles were anovulatory (P < 0.02). Five THC-treated animals were anovulatory in the posttreatment cycle. To determine the site of action of THC-induced anovulation, five animals received THC, human menopausal gonadotropin, and hCG simultaneously. All ovulated normally, as determined by laparoscopic visualization of stigma. Normal luteal phases were evidenced by normal luteal phase lengths and serum progesterone concentrations. These findings are of clinical relevance, since they were achieved with doses of THC that produce blood concentrations similar to those found in heavy marijuana users.

Animals↗
PubMed1981

Luteolytic effect of D-Trp6-luteinizing hormone-releasing hormone in the rhesus monkey (Macaca mulatta).

A potent agonist of luteinizing hormone, D-Trp6-LRH, was administered at different stages during the luteal phase of rhesus monkeys (Macaca mulatta). Luteolysis, evidenced by short luteal phases and decreased serum progesterone concentrations, was consistently induced when the analog was injected on days 3 or 5 post ovulation; however, no effect was observed when it was given on day 7 post ovulation. Increasing doses of hCG administered from days 6-10 post ovulation prevented the luteolytic effect of D-Trp6-LRH. The possible mechanisms of action and the potential uses of LRH analogs as contraceptive agents are discussed.

Animals↗
PubMed1981

Glucocorticoid suppression of pituitary prolactin release in the nonhuman primate.

The administration of 8 mg dexamethasone daily for 8 days significantly lowered basal and TRH-stimulated PRL levels in ovariectomized rhesus monkeys. A single acute injection of dexamethasone attenuated the total amount of PRL released after TRH stimulation, although basal and peak PRL levels were not significantly different from those found in controls. In an attempt to determine the site of action of glucocorticoids on PRL secretion, baboon pituitaries were incubated with cortisol. Cortisol at a concentration of 3 x 10(-5) M significantly inhibited PRL secretion in vitro, while a concentration of 3 x 10(-4) M was needed to block TRH-stimulated prolactin release. In conclusion, glucocorticoids can suppress pituitary PRL secretion by a direct action on the pituitary gland, although a hypothalamic site of action may also be involved.

Animals↗
PubMed1981

Interactions of cocaine and delta 9-tetrahydrocannabinol with the hypothalamic-hypophysial axis of the female rat.

The acute effects of cocaine and/or delta 9-tetrahydrocannabinol (THC) were studied in ovariectomized female rats. Intermediate doses of cocaine (10 or 20 mg/kg) caused an increase in serum luteinizing hormone (LH) and a decrease in serum prolactin levels, whereas a higher dose (40 mg/kg) caused a decrease in serum LH. THC (10 mg/kg) attenuated serum LH and prolactin levels. The THC effect on LH was blocked by cocaine. Neither drug alone or in combination affected serum follicle-stimulating hormone levels. The cocaine-induced changes in LH levels were closely paralleled by changes in hypothalamic norepinephrine content, suggesting a neurochemical basis for cocaine's action on LH release.

Animals↗
PubMed1981

Effects of hCG on prostaglandin synthesis and function of corpus luteum.

The effect of intramuscular injections of human chorionic gonadotropin (hCG) on subsequent in vitro prostaglandin (PG) production by the corpus luteum was studied in the rhesus monkey. Four monkeys received increasing doses of hCG from days 6 to 10 after ovulation. On day 11, laparotomy and luteectomy were performed. Five untreated animals served as controls. The production of prostaglandins F (PGF) and E (PGE) by the corpus luteum of the animals treated wit hCG was significantly lower than that of the controls (P less than .01). After hCG treatment, the decrease in PGF production was greater than that of PGE, resulting in a lower ratio of PGF:PGE production than in the controls (P less than .01). Histologic evaluation of the corpora lutea revealed regressive changes in the control group, whereas signs of active secretion were observed in the hCG-treated group. Progesterone concentrations in peripheral blood of the hCG-treated group were approximately fourfold higher than in the controls, and the hCG-treated group did not have a postmidluteal phase decrease. These results suggest that the ratio of production of PGF to PGE by the corpus luteum of the rhesus monkey may play a role in the control of its lifespan and steroidogenic capacity.

Animals↗
PubMed1980

Danazol for benign breast disease.

Three groups of women with benign breast disease were treated with danazol for 3 to 6 months. Doses of 100 mg per day were given to 40 patients, 200 mg to 55, and 400 mg to 35. The age range of the patients was 20 to 48 years. The patients were rechecked at 6-month intervals over a period of 48 months. Most of them were seen four or more times after completion of therapy. Elimination of nodularity occurred in about two thirds; three experienced no improvement, and partial resolution was obtained in the remainder. Untoward effects were minimal or trivial. Danazol proved to be an excellent hormonal agent in the management of fibrocystic disease of the breast.

Adult↗
PubMed1980

Mechanism of induction of luteal phase defects by danazol.

The effects of danazol on the luteal phase of cycling rhesus monkeys and on the ability of the intact rhesus monkey to respond to hCG stimulation were studied in two experiments. In a third experiment the impact of danazol upon the response of the decapsulated mouse testis to hCG stimulation was evaluated. These experiments demonstrated that danazol shortens the luteal phase and decreases progesterone production in intact monkeys via a direct effect on the gonad.

Animals↗
PubMed1980

Danazol binding and translocation of steroid receptors.

Danazol, an isoxazol derivative of ethinyl testosterone which suppresses gonadotropin levels and acts as a weak androgen, is shown by competition studies to bind rat androgen receptor (Ki 10(-8M) and progestin receptor (Ki 10(-7)M) but not estrogen receptor. Effective antigonadotropin doses to the rat in vivo translocate only androgen receptor to target cell nuclei; nuclear receptor levels remain elevated more than 6 hours. The same translocation occurs when rat uteri are incubated with danazol in vitro, showing that the action of danazol is direct and probably does not require metabolic conversion of the drug.

Animals↗
PubMed1980

Pelvic adhesions following microsurgical and macrosurgical wedge resection of the ovaries.

The incidence of postoperative adhesion formation following microsurgical and macrosurgical ovarian wedge resection was contrasted in 10 adult female rhesus monkeys. Bilateral wedge resection was performed on day 10 of the luteal phase using microsurgical technique on one ovary and macrosurgical technique contralaterally. Animals were examined 4 weeks postoperatively. Adhesion formation occurred in only one ovary in which microsurgery had been employed (10%). In contrast, adhesion formation followed macroscopic ovarian wedge resection in five ovaries (50%). All adhesions were periovarian, emanating from the suture line on the ovarian surface. Adhesions were most common on the nonovulatory ovary.

Animals↗