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Biomedical subjects

R F Casper

Publications and source records attributed to R F Casper.

At least 145 records · Page 8Linked to original sources
PubMed1984

Studies on the effect of gonadotropin-releasing hormone and its agonist on human luteal steroidogenesis in vitro.

The possible direct effect of gonadotropin-releasing hormone (GnRH) and a potent GnRH agonist [( imBzl )-D- His6 -Pro9-NEt]-GnRH on basal and human chorionic gonadotropin (hCG)-stimulated progesterone, androstenedione, and estradiol production by cultured human luteal cells was examined. Luteal cells from the early or midluteal phase of the menstrual cycle responded to hCG stimulation with two to fivefold increases in steroid production in both short-term (4 hours) and long-term (up to 144 hours) culture in chemically defined medium without serum. After 48 hours in this system, levels of androstenedione and estradiol were very low, and progesterone was the predominant steroid produced. The addition of GnRH or a potent GnRH agonist to the medium had no effect on either basal or hCG-stimulated steroid secretion. When luteal cells were cultured longer (for up to 10 days) in the presence of serum, GnRH agonist caused no significant alteration of either basal or hCG-stimulated progesterone production. Collectively, these results support the conclusion that GnRH and its potent agonist do not act directly on human corpora luteal cells to modulate steroidogenesis.

Androstenedione↗
PubMed1984

Prolonged elevation of hypothalamic opioid peptide activity in women taking oral contraceptives.

To examine the hypothesis that endogenous opioid peptide activity is chronically elevated by oral contraceptives, we infused either naloxone or saline into 10 women during the use of, or 5-6 and 9-10 days after stopping, combination birth control pills. A paradoxical increase in prolactin occurred with naloxone infusion during and 5-6 days after stopping the pills. Serum LH levels were not significantly elevated by naloxone until 9-10 days after cessation of pill use. These results suggest that hypothalamic opioid peptide activity is continuously elevated in women taking oral contraceptives.

Adult↗
PubMed1984

The postcoital test as a predictor of pregnancy among 355 infertile couples.

Late follicular phase postcoital tests in 355 infertile couples (selected to exclude severe defects in ovulation, seminal or tubal function) were scored for mucus characteristics and sperm motility. Cervical mucus characteristics were associated with postcoital sperm motility (P less than 0.001) but not with pregnancy. Postcoital sperm motility in cervical mucus was strongly associated with total motile sperm count per ejaculate (F = 5.38, P less than 0.001). Postcoital sperm motility was a weak predictor of pregnancy when more than five motile sperm were observed per high power microscopic field. When the log rank tests for postcoital sperm motility were repeated in groups with low (less than 10 million) and high (10 million or more) total motile sperm count per ejaculate, the association between postcoital sperm motility and pregnancy was not statistically significant. Regression analysis controlling for other potential predictors revealed no independent association between postcoital sperm motility and the later occurrence of pregnancy in this group of infertile couples.

Adult↗
PubMed1983

Initiation of parturition in humans.

The mechanism by which parturition is initiated in humans is largely unknown. The placenta and fetal membranes appear to play the major role in the initiation of labour, and the fetus may influence the timing of labour. Clinical observations and experiments with animals have revealed that placental neuropeptides may be able to control steroid metabolism and trigger the onset of labour, while the fetus may be able to interact with such events to initiate parturition at an appropriate time. However, further study is needed to determine the role of placental releasing factors and glycoprotein hormones and their ability to control placental steroid metabolism.

Actins↗
PubMed1982

Luteal phase defects induced by an agonist of luteinizing hormone-releasing factor: a model for fertility control.

Subcutaneous injection of 50 micrograms of a luteinizing hormone-releasing factor agonist (LRF agonist) for three successive days at the time of menstruation in normal cycling women induces a shortened luteal phase with suboptimal concentrations of circulating estradiol and progesterone. This luteal phase defect follows a reduced concentration of follicle-stimulating hormone during the follicular phase and a resulting inadequate follicular maturation. Since a short luteal phase is associated with an endometrium not conductive to implantation, administration of the LRF agonist at the onset of menstrual cycle may prove to be a practical and novel approach to fertility control.

Adult↗
PubMed1982

The effect of luteinizing hormone-releasing factor and its agonist on cultured human granulosa cells.

The possible direct effect of luteinizing hormone-releasing factor (LRF) and a potent LRF agonist, [D-Trp6,Pro9NEt]-LRF (LRF-Ag), on basal and follicle-stimulating hormone (FSH)-stimulated estrogen and progesterone production by cultured human granulosa cells was examined. Granulosa cells, collected from healthy follicles (4 to 12 mm in diameter) in the early to midfollicular phase were grown for 2 days in serum-free medium with aromatase substrate (androstenedione; 10(-7) M) and human FSH (100 ng/ml), LRF (10(-10) to 10(-7) M) or in LRF-Ag (10(-7) M). Granulosa cells from each follicle responded to FSH stimulation by showing marked increases (2- to 20-fold) in estrogen and progesterone production. Concomitant treatment with high doses of LRF or LRF-Ag did not alter the steroidogenic effect of FSH. These results suggest that in contrast to the rat, LRF and its agonistic analog do not act directly on human granulosa cells to inhibit acute steroidogenic function.

Adult↗
PubMed1982

Induction of luteolysis by luteinizing hormone-releasing factor (LRF) agonist: sensitivity, reproducibility, and reversibility.

The reproducibility, reversibility, and the maximal effectiveness of the luteolytic action of [D-Trp6,Pro9NEt]-LRF (luteinizing hormone-releasing factor) (LRF-agonist) were evaluated during 43 treatment cycles in 15 normal women. LRF-Ag (50 microgram) administration subcutaneously on 1 or 2 days at varying times during the luteal phase of consecutive cycles was made. Successful luteolysis was achieved in 26 of 27 cycles (96%) in which LRF-Ag was administered between 5 and 8 days after the luteinizing hormone (LH) peak. However, LRF-Ag treatment failed to induce luteolysis in 10 of 13 cycles (77%) when treatment began within 5 days of the LH peak. The luteal phase of posttreatment cycles was functionally unaffected by prior LRF-Ag treatment. The present study has thus demonstrated the reproducibility and reversibility of LRF-Ag as a potent luteolytic agent, although its action is dependent upon the timing of administration with a window of maximal effectiveness on days 5 to 8 of the luteal phase.

Adult↗
PubMed1981

In vitro heteroregulation of LH receptors by prolactin and FSH in rat granulosa cells.

The purpose of the present study was to further characterize the regulation of LH/hCG receptors by FSH in granulosa cells and test the hypothesis that the LH/hCG receptor levels are heteroregulated by PRL. Granulosa cells from immature hypophysectomized, DES-treated rats were cultured for 2-4 days in defined medium containing androstenedione (10(-7) M) and/or FSH and PRL, after which [125I]iodo-hCG binding to the granulosa cells was measured. When granulosa cells were cultured for 2 days (days 0-2) with increasing concentrations of FSH (0.1-100 ng/ml), there was a dose related increase in [125I]iode-hCG binding from a control value of 1.05 +/- 0.2 fmoles/10(6) cells to a maximum of 20 +/- 1.8 fmoles/10(6) cells. The miminum, half-maximum (ED50) and maximum doses of FSH were 0.3, 0.5 and 3 ng/ml, respectively. At concentrations of FSH greater than 3 ng/ml there was a progressive decrease in [125I]-iodo-hCG binding to a low value of 6.1 +/- 1 fmoles/10(6) cells at 100 ng/ml of FSH. No changes in [125I]iodo-hCG binding were observed in response to PRL (1 microgram/ml) during the day 0-2 incubation. When granulosa cells were stimulated for 2 days with 20 ng/ml of FSH, washed, and then recultured for another 2 days (days 2-4) with FSH, the LH/hCG receptor content remained high (F leads to F = 17.4 +/- 2.8 fmoles/10(6) cells). In contrast, when FSH-primed cells were recultured for 2 days without FSH, the [125I]iodo-hCG binding decreased sharply to near control levels (F leads to C = 2.5 +/- 0.2 fmoles/10(6) cells). This marked loss of LH/hCG receptors was largely prevented when FSH primed cells were recultured with PRL (F leads to P = 10.3 +/- 1.5 fmoles/10(6) cells). This stimulatory effect of PRL on [125I]iodo-hCG binding was dose-dependent: minimum, ED50, and maximum doses of PRL were 0.2, 0.5 and 1 microgram/ml, respectively. Scatchard-plot analysis revealed that although the dissociation constant (Kd) of the LH/hCG receptors stimulated by FSH and PRL were of similar high affinity (approximately 8 x 10(-11) M), the maximum binding (Bmax) values in the PRL-treated cells were less. Addition of 10(-7) estradiol together with the PRL did not cause a further increase in Bmax values above that observed with PRL alone.

Animals↗
PubMed1981

Intravaginal administration of progesterone: enhanced absorption after estrogen treatment.

A progesterone solution was administered by intravaginal instillation, intramuscular injection, and sublingually to estrogen-deficient women, with or without estradiol (E2) replacement, and serum progesterone (P) concentrations were measured by radioimmunoassay. Intravaginal application to postmenopausal subjects receiving E2 gave the highest values of serum P: 10 times baseline at 15 minutes and 30 to 40 times at 1 to 2 hours, with sustained levels, for 7 hours and decline to 10 times baseline at 24 hours. Intravaginal application to hypoestrogenic women gave similar results, but of much lower magnitude (highest value, 20 times baseline). Intramuscular injection, in contradistinction, showed gradually increasing levels over the study period, up to 30 times basal values at 24 hours. It contrast, sublingual application produced very modest serum increases, to approximately 10 times baseline within 2 hours and return to basal value at 24 hours. Since the most rapid and highest levels were observed by vaginal application to postmenopausal women receiving estrogen, and considering that the vagina has been similarly shown to be very effective for estrogen absorption, it is conceived that full hormone replacement could be accomplished in the deficient states by cyclic vaginal application of both steroids.

Absorption↗
PubMed1981

Simultaneous pulsatile release of prolactin and luteinizing hormone induced by luteinizing hormone-releasing factor agonist.

Subcutaneous injection of 50 microgram long acting agonist of LRF (LRF-Ag) resulted in the prompt, simultaneous pulsatile release of both LH and PRL in four hypogonadal women. After repeated daily administration of LRF-Ag. LH release in response to LRF-Ag was markedly attenuated, and LH pulses were abolished. LRF-Ag induced PRL release was also attenuated but remained pulsatile. These findings demonstrate the dissociation of the LRF-Ag-induced contemporaneous release of LH and PRL and suggest a hypothalamic site of action of LRF-Ag on PRL release.

Estradiol↗
PubMed1981

Menopausal flushes: effect of pituitary gonadotropin desensitization by a potent luteinizing hormone- releasing factor agonist.

Recent evidence suggests that the menopausal flush is linked to the neuroendocrine events which govern pulsatile LH secretion and thermoregulation. This study was designed to determine whether abolishment of LH pulses may abate flush episodes. After pituitary gonadotropin densensitization by a LRF agonist, LH and FSH pulses were abolished, and serum gonadotropin levels were decreased. Flush episodes, however, were unaltered. These findings demonstrate that pulsatile LH release by the pituitary is not causally related to menopausal flushes, and support the contention that flush episodes are initiated by a hypothalamic mechanism(s).

Body Temperature↗
PubMed1981

Rapid absorption of micronized estradiol-17 beta following sublingual administration.

The effect of sublingual administration of 2 mg of micronized estradiol-17 beta (E2) on circulating concentrations of estrone (E1), E2, luteinizing hormone, and follicle-stimulating hormone was evaluated. Six women were studied during the early follicular phase, along with 3 hypogonadal women. Absorption of E2 was extremely rapid with a respective 9-fold and 41-fold increase over basal serum levels within 30 minutes. However, for most of the 24-hour period studied, E1 rather than E2 was the predominant circulating estrogen. Although physiologic levels of E2 can be maintained, it would appear that the sublingual route is not ideal for E2 replacement, as concomitant superphysiologic elevation of circulating E1 occurs.

Absorption↗
PubMed1980

Changes in pituitary hormones during and following transsphenoidal removal of prolactinomas.

Prolactin (PRL) and other pituitary hormones (luteinizing hormone, follicle-stimulating hormone, growth hormone [GH], thyrotropin stimulating hormone) were measured before, during, and after transphenoidal pituitary adenomectomy in 16 patients with hyperprolactinemia. The diagnosis of prolactinoma was made in three of the 16 patients by the absence of PRL response to thyrotropin-releasing factor (TRF) and a dopamine receptor antagonist, metoclopramide, without radiologic evidence of an adenoma. Contrary to findings in subjects with normal PRL values, the PRL rise in response to anesthesia and operation was absent. Other pituitary hormones, with the exception of GH, which increased during anesthesia and operation, exhibited no acute changes. In 11 of 16 cases, complete tumor removal was achieved as determined by the rapid decline of PRL levels to normal values within 24 to 48 hours after operation and by subsequent clinical follow-up. This finding documents that the adenoma is the main source of excessive PRL secretion. The circulating half time of immunoreactive PRL determined by frequent sampling in these patients was variable, ranging from 74 to 190 minutes, significantly longer than the previously reported value of 15 minutes determined by bioassay. Although a transient decline was evident, serum PRL levels remained elevated in those patients with incomplete tumor removal. These findings suggest that a single measurement of serum PRL within 24 to 48 following transphenoidal adenomectomy is a reliable indicator of the success or failure of the procedure.

Adenoma↗
PubMed1980

Chorionic gonadotropin prevents LRF-agonist-induced luteolysis in the human.

The effects of exogenous and endogenous hCG on the luteolytic action of LRF-agonist, [D-Trp6, Pro9NEt]-LRF (LRF-Ag), were evaluated. In sequential studies, 4 normal cycling women treated with LRF-Ag (50 microgram S.C.) on two consecutive days had premature decline of circulating levels of progesterone (P) and estradiol (E2) with a shortened (p < 0.05) luteal phase (11.5 +/- 1.2 days) when compared to the control cycle (15 +/- 0.7 days). When intramuscular hCG was added to the LRF-Ag treatment in doses of 100 IU or 5000 IU daily for 7 days, the luteal function was prolonged (19 +/- 1.2 days, p < 0.05) with significant (p < 0.001) elevation of P and E2 levels compared with the control cycle. Four women with early pregnancy, requesting therapeutic abortion, were given LRF-Ag (50 microgram or 500 microgram S.C.) on 2 consecutive days. None of the 4 women aborted and there was no change in the levels of beta hCG, P or E2 over the course of a week. These results indicate that both exogenous or endogenous hCG can overcome the luteolytic effect of LRF-Ag within the dose and duration used. The possibility that a more prolonged administration of a larger dose of LRF-Ag may negate the luteotropic effect of hCG remains to be explored.

Chorionic Gonadotropin↗
PubMed1980

Gonadotropin-estradiol responses to a superactive luteinizing hormone-releasing hormone agonist in women.

After the sc administration of 1, 10, and 50 micrograms of the LRF agonist [D-Trp6,Pro9,NEt]LRF, dose-dependent increments in circulating levels of LH, FSH, and estradiol were observed which were 2- to 3-fold greater in the late than in the early follicular phase. The 10-microgram dose of LFR agonist appears to induce a maximal acute gonadotropin-estradiol response. Both 10- and 50-microgram doses of the agonist elicited gonadotropin increments which were several times greater than that seen during the midcycle surge. The only difference between the two doses was the more sustained action on gonadotropin release of the latter. It is estimated that this superactive LRF agonist is approximately 140 times more potent than the decapeptide LRF. These observations provide information useful in the application of this LRF agonist for clinical studies.

Adult↗
PubMed1980

Evidence for an increased opioid inhibition of luteinizing hormone secretion in hyperprolactinemic patients with pituitary microadenoma.

The inhibiting role of endogenous opioid peptides on gonadotropin secretion was evaluated by the infusion of an opioid receptor antagonist, naloxone (1.6 mg/h for 4 h), in 10 hyperprolactinemic patients with pituitary microadenoma (prolactinoma) and 5 normal women during the early follicular phase of the cycle. In normal women, naloxone infusion induced no significant changes in any of the three pituitary hormones measured. Six prolactinoma patients with low normal levels of basal LH [10.0 +/- 1.0 mIU/ml +/- SE)] responded to naloxone infusion with an increment of circulating LH in the form of an amplified pulsatile pattern of release, which lasted for at least 2 h after the infusion. The other 4 patients with prepubertal levels of LH (4.9 +/- 0.8 mIU/ml) exhibited no LH response to naloxone. There were no significant changes in FSH or PRL levels in either group of patients. These findings suggest that an increased endogenous opioid inhibition of LH release occurs in patients with PRL-producing microadenoma.

Adenoma↗