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Biomedical subjects

B H Yuen

Publications and source records attributed to B H Yuen.

At least 73 records · Page 4Linked to original sources

Differential effects of 8-bromo-cyclic AMP on human chorionic gonadotropin (hCG), progesterone and estrogen production by term placental cells.

The present study examined the effects of a cAMP analog on the output of hCG and progesterone (P) in human term trophoblast cells in culture, as well as the conversion of androstenedione and testosterone to estradiol--17 beta and estrone by these cells. The levels of hCG and P in the culture medium increased throughout the four-day culture period. Addition of 8-bromo-adenosine-3',5'-monophosphate (8-Br-cAMP), forskolin or cholera toxin (but not 8-Br-cGMP) stimulated hCG and P production by the cultivated placental cells. In contrast, the presence of 8-Br-cAMP for 2 days significantly decreased basal estradiol-17 beta output, as well as conversion of androstenedione to estradiol-17 beta; the conversion of androstenedione to estrone was not affected. 8-Br-cAMP attenuated the conversion of testosterone to both estradiol-17 beta and estrone. These results further support the view that cAMP could have both stimulatory and inhibitory actions on placental hormonogenesis.

8-Bromo Cyclic Adenosine Monophosphate↗

Direct effects of clomiphene citrate on the steroidogenic capability of human granulosa cells.

The effects of clomiphene citrate (CC), 17 beta-estradiol (E2), and human chorionic gonadotropin (hCG) on the accumulation of progesterone (P) and 20 alpha-hydroxy-4-pregnen-3-one (20 alpha-OHP) in cultured human granulosa cells (GC) were examined. In addition, the metabolism of [4-14C]pregnenolone and accumulation of [4-14C]P in response to CC and E2 were determined. The authors conclude the following: (1) the dose-dependent inhibition of P and 20 alpha-OHP production by CC in GC was not reproduced by E2, (2) hCG abolished these effects of CC, (3) these inhibitory actions of CC were not associated with altered 3 beta-hydroxysteroid dehydrogenase activity nor P catabolism indicating that, (4) these actions by CC on the GC occur at some step(s) during steroidogenesis preceding the formation of pregnenolone. These findings may explain, at least in part, the luteal deficiency experienced by women treated with CC, and they also provide a rationale for the use of hCG supplementation during ovulation induction with CC.

20-alpha-Dihydroprogesterone↗

Effects of an antiandrogen, flutamide, on oocyte quality and embryo development in rats superovulated with pregnant mare's serum gonadotropin.

Increased oocyte degeneration in rats is associated with enhanced ovarian androgen secretion following superovulation with pregnant mare's serum gonadotropin (PMSG). To determine whether androgens may be causally related to oocyte degeneration, we examined the effects of an antiandrogen, flutamide, on oocyte quality and embryo development after induction of superovulation with PMSG. Immature female Sprague-Dawley rats were used for two experiments. In the first experiment, the females received either 5 mg flutamide or vehicle alone 30 and 36 h after 40 IU PMSG and were killed at 48, 60, and 72 h. Although total number of oocytes was not significantly different between the two groups, flutamide significantly reduced the percentage of degenerate oocytes ovulated at all the time intervals examined (p less than 0.01). In the second experiment, the females were given 4 IU PMSG (control) or 40 IU PMSG with either 5 mg flutamide or vehicle. The rats were mated and then killed on Days 2, 3, 4, and 5 of pregnancy. Compared to control, flutamide did not effectively prevent the early loss of preimplantation embryos nor the developmental retardation which took place in the vehicle-treated rats after Day 2. However, flutamide treatment was associated with a significant decrease in embryo degeneration and a significant increase in the percentage of cleaved embryos on Day 2 (p less than 0.01). Compared to levels associated with the vehicle regimen, ovarian and/or serum androgen levels in the flutamide-treated rats significantly decreased at 60 h (p less than 0.01) and on Day 2 (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗

Time-dependent effects of follicle-stimulating hormone on progesterone metabolism by cultured rat granulosa cells.

The effects of FSH on the accumulation of endogenous progesterone and 20 alpha-hydroxy-4-pregnen-3-one as well as on the metabolism of [4-14C]progesterone were studied in 24, 48 and 72 h cultures of rat granulosa cells. FSH stimulated the accumulation of both progesterone and 20 alpha-hydroxy-4-pregnen-3-one by 6-18 fold and 2.5-44 fold, respectively. Short term exposure (24 h) to FSH resulted in the ratio of progesterone to 20 alpha-hydroxy-4-pregnen-3-one accumulations significantly increased (by 2.6 fold), while the reverse was observed for the longer (48 and 72 h) cultures whereby control levels of the ratio of progesterone to 20-alpha-hydroxy-4-pregnen-3-one were significantly greater (by 50% and 270%, respectively) than those of FSH-treated cultures. Effects of FSH on [4-14C]progesterone were also time-dependent. Twenty-four hour cultures were associated with FSH induced inhibition of 20 alpha-reduced metabolites of progesterone (by 55%) while the 48 and 72 h exposures to FSH resulted in a significant increase of the 20 alpha-reduced metabolites above control levels (by 73% and 230%, respectively). Consequently, it is postulated that FSH may exert biphasic time-dependent actions on 20 alpha-hydroxysteroid dehydrogenase activity with short term inhibitory and longer term stimulatory effects.

20-Hydroxysteroid Dehydrogenases↗

Effects of superovulatory doses of pregnant mare serum gonadotropin on oocyte quality and ovulatory and steroid hormone responses in rats.

Immature rats (aged 28 days) were injected with 4, 20, or 40 IU pregnant mare serum gonadotropin (PMSG) and sacrificed every 6 or 12 hr. Control rats (4 IU) ovulated between 60 and 72 hr, whereas rats given superovulatory doses of PMSG (20 and 40 IU) ovulated between 24 and 72 hr. The oocyte count from the superovulated rats increased slightly between 24 and 36 hr and markedly between 48 and 72 hr. Degenerated oocytes were recovered 48 and 36 hr after administration of 20 and 40 IU PMSG, respectively. Thereafter, the proportion of degenerated oocytes was dose dependent and reached a maximum at 72 (30.9%, 20 IU) and 60 hr (61.0%, 40 IU). 17 beta-estradiol content of the superovulated ovaries increased significantly (P less than 0.01) from 36 hr and was maximal at 60 (20 IU) or 54 hr (40 IU), when compared to the control regimen. Administration of 40 IU PMSG resulted in a biphasic increase of progesterone content with the peaks at 36 and 60 hr. Androgen content of the superovulated ovaries was lower than control levels during the first 36 hr but was significantly (P less than 0.01) higher thereafter. The results suggest that these alterations in the steroid response (particularly androgens) from 36 hr onward following superovulation may be responsible for the coincidental occurrence of abnormal oocytes, possibly by disturbing the specific intrafollicular steroid environment essential for complete maturation. In addition, oocyte aging that is due to earlier activation by the exogenous luteinizing hormone activity may be a contributing factor.

Androgens↗

Human chorionic gonadotropin, prolactin, estriol, and dehydroepiandrosterone sulfate concentrations in cord blood of premature and term newborn infants: relationship to the sex of the neonate.

Although the composition of human chorionic gonadotropin, prolactin, estriol, and dehydroepiandrosterone sulfate in the umbilical cord blood has been studied, less information is available on the effect of fetal sex on the cord blood concentrations. We assayed these hormones in cord blood from 405 newborn infants delivered between 23 and 43 weeks of gestation. In pooled data for both sexes, human chorionic gonadotropin showed a declining trend from the beginning to the end of the sampling interval. By contrast, in 398 newborn infants of known sex, prolactin, estriol, and dehydroepiandrosterone sulfate levels increased during the same period. Sex differences were observed for human chorionic gonadotropin only; female newborn infants had higher cord blood concentrations throughout the sampling period, with the differences becoming statistically significant between 29 and 36 weeks.

Chorionic Gonadotropin↗

Differing concentrations of human chorionic gonadotropin and prolactin in the cyst fluid of hydatidiform mole and in amniotic fluid.

The concentrations of human chorionic gonadotropin and prolactin in the cyst fluid of molar tissue were compared with that of normal amniotic fluid. Molar fluid was aspirated from the vesicles of molar tissue in eight women (duration of amenorrhea 14.1 +/- 1 week, mean +/- SEM). Amniotic fluid was obtained at amniocentesis in 24 women (mean duration of amenorrhea 15.9 +/- 0.2 week). Hormones were measured by specific radioimmunoassay. The concentrations (mean +/- SEM) of human chorionic gonadotropin in molar fluid and amniotic fluid were 581,829 +/- 112,581 and 3187 +/- 505 mlU/ml (p less than 0.001), respectively. For prolactin the levels in molar fluid and amniotic fluid were 44 +/- 24 and 1962 +/- 313 ng/ml (p less than 0.001), respectively. These data demonstrate that molar fluid contains 182-fold higher levels of human chorionic gonadotropin and 45-fold lower levels of prolactin than amniotic fluid obtained from normal pregnant women with a similar duration of amenorrhea. In addition to altered endocrine function of the trophoblast, there may be altered prolactin secretion from the decidua in molar pregnancy as compared with normal pregnancy. Further research is required to evaluate prolactin production from decidua of molar pregnancy.

Adult↗

Effects of adenosine 3',5'-cyclic monophosphate, forskolin, and cholera toxin on hormone production in human term placental cells.

Trophoblast cells from human term placenta in monolayer culture were used to investigate the role of adenosine 3',5'-cyclic monophosphate in the production of human chorionic gonadotropin and estradiol-17 beta. The intracellular concentration of adenosine 3',5'-cyclic monophosphate was elevated by (1) addition of an adenosine 3',5'-cyclic monophosphate analogue, 8-bromoadenosine 3',5'-cyclic monophosphate, (2) inhibition of the hydrolysis of Gs-GTP complex by cholera toxin, and (3) direct stimulation of adenylate cyclase with forskolin. Addition of 2 mmol/L of 8-bromoadenosine 3',5'-cyclic monophosphate markedly increased the accumulation of human chorionic gonadotropin in the culture medium on days 2, 3, and 4 of treatment. Likewise, addition of cholera toxin (0.2 microgram/ml) or forskolin (50 mumol/L) also enhanced human chorionic gonadotropin production. On the other hand, the production of estradiol-17 beta was significantly inhibited by 8-bromoadenosine 3',5'-cyclic monophosphate, at the same time that human chorionic gonadotropin production was enhanced in the same experiments. These results further support a differential role of adenosine 3',5'-cyclic monophosphate on human chorionic gonadotropin and estradiol-17 beta production in the human term placenta.

Cholera Toxin↗

Actions of LH/hCG on accumulation and catabolism of progestins in cultured rat granulosa cells.

Immature hypophysectomized rats were treated with estradiol-17 beta and follicle-stimulating hormone. Granulosa cells were isolated and incubated for 24 h with or without varying doses of ovine luteinizing hormone (NIMADD-oLH-24) or human chorionic gonadotropin (NIADDK CR 125) and accumulations of progesterone and 20 alpha-hydroxy-4-pregnen-3-one were determined. The cells were reincubated for 3 h with [4-14C]progesterone (0.5 nmol/mL) and the radiolabelled metabolites were separated and quantified. Both LH (0.04-1.0 ug/mL) and hCG (0.04-1.0 ug/mL) enhanced the accumulation of endogenous progesterone (by up to 300 and 150%, respectively) and 20 alpha-hydroxy-4-pregnen-3-one (by up to 90 and 85%, respectively) producing dose-dependent increases of the ratio of progesterone to 20 alpha-hydroxy-4-pregnen-3-one (by up to 125 and 70%, respectively). Studies of the metabolism of [1-14C] progesterone have demonstrated that both LH and hCG led to a dose-dependent decrease of the utilization of radiolabelled progesterone (down to 64 and 70%, respectively, of the control value). This effect was associated with an LH- and hCG-dependent inhibition of 20 alpha-hydroxysteroid dehydrogenase activity (down to 60 and 70%, respectively, of the control value) but had no significant effect on 5 alpha-reductase. The present results indicate that LH and hCG stimulate accumulation of progesterone at least in part by decreasing the 20 alpha-hydroxysteroid dehydrogenase activity.

20-Hydroxysteroid Dehydrogenases↗

Effects of prostaglandins E2 and F2 alpha on progesterone metabolism by rat granulosa cells.

Rat granulosa cells were cultured with or without PGE2 and/or PGF2 alpha. Accumulation of endogenous progesterone and 20 alpha-hydroxy-4-pregnen-3-one was determined. Additionally, [4-14C]progesterone metabolism was assessed. PGE2 increased progesterone accumulation, in part, by decreasing progesterone catabolism to 20 alpha-reduced progestins. In contrast, PGF2 alpha stimulated 20 alpha-hydroxysteroid dehydrogenase activity, thus increasing progesterone catabolism. Combined treatment with PGE2 and PGF2 alpha augmented progesterone accumulation to levels above controls but below those attained with PGE2 alone. These data indicate that PGE2 and PGF2 alpha exert opposite effects on progesterone production and catabolism and that the ratio of PGE2 to PGF2 alpha in the local granulosa cell milieu may be of importance in determining overall progesterone output.

Animals↗

Occurrence of molar pregnancy in patients undergoing elective abortion: comparison with other clinical presentations.

Clinical data of molar pregnancies found in women undergoing elective abortion (group 1, n = 39) were compared to those of molar pregnancies in women who experienced spontaneous abortions (group 2, n = 157) and women in whom molar pregnancy was discovered before symptoms of spontaneous abortion were evident (group 3, n = 209). Group 1 women were younger and experienced uterine evacuation at an earlier stage of amenorrhea than groups 2 and 3. Group 3 had larger uteri at evacuation and longer intervals of positive tests for the beta-subunit of human chorionic gonadotropin during the postmolar phase as compared with groups 1 and 2. On the basis of available provincial data for the number of elective abortions, the estimated incidence of molar pregnancies in this population was 1:2,699. The presence of malignant gestational trophoblastic neoplasia was documented in a single patient in group 1. The incidence of malignant gestational trophoblastic neoplasia in this group was not significantly different from that in groups 2 and 3. Routine pathologic examination of the products of conception in women undergoing elective abortion coupled with routine assays of the beta-subunit of human chorionic gonadotropin when molar pregnancy is found can identify both noninvasive and invasive trophoblastic disease in these women.

Abortion, Induced↗

Inhibition of human chorionic gonadotropin production by prolactin from term human trophoblast.

In vivo suppression of prolactin concentrations by bromocriptine near term, in a pregnant woman with a prolactinoma, was followed by augmentation of human chorionic gonadotropin levels. Suspension of drug therapy at 38 weeks of gestation was followed by a reversal of this sequence of events. In vitro, both ovine prolactin and human prolactin added to explants of term placental trophoblast significantly inhibited human chorionic gonadotropin production from this tissue. Although, with ovine prolactin, this inhibitory effect was demonstrable up to 5 micrograms/ml of ovine prolactin in the culture medium, only doses of 0.1 to 0.2 micrograms/ml of human prolactin significantly suppressed human chorionic gonadotropin production. Overall, 0.1 and 0.2 micrograms/ml of ovine prolactin and human prolactin most consistently suppressed human chorionic gonadotropin production to a statistically significant extent. In general, the concentrations in the culture medium of both ovine prolactin and human prolactin that inhibited human chorionic gonadotropin production in vitro were comparable to the concentrations of prolactin present in the mother and fetus. These in vivo and in vitro observations suggest that prolactin inhibits human chorionic gonadotropin production from term human trophoblast.

Adult↗

Relationship of gonadotropin-releasing hormone, danazol, and prostaglandin blockade to ovarian enlargement and ascites formation of the ovarian hyperstimulation syndrome in the rabbit.

The effects of pharmacologic doses of gonadotropin-releasing hormone, danazol, and indomethacin on the clinical and endocrinologic features of the ovarian hyperstimulation syndrome were studied in the rabbit. The ovarian hyperstimulation syndrome was induced with Pergonal (75 IU of follicle-stimulating hormone and 75 IU of luteinizing hormone) and a follicle-stimulating hormone-dominant gonadotropin preparation (85 IU of follicle-stimulating hormone and 53 IU of luteinizing hormone). None of the three agents tested were effective in suppressing the ovarian enlargement and ascites formation in these animals. Ascites developed despite quite significant variations in plasma and intraovarian sex steroid hormone and intraovarian prostaglandin F levels induced by danazol and indomethacin. Ascites develops in hyperstimulated women in association with both follicular and luteal hyperstimulation. In contrast, the ascites response in the hyperstimulated rabbit develops in the presence of follicular hyperstimulation alone without a significant degree of luteal hyperstimulation.

Animals↗

Comparison of the outcome of ovulation induction therapy in an in vitro fertilization program employing a low-dose and an individually adjusted high-dose schedule of human menopausal gonadotropins.

A low-dose "nonsuperovulation" scheme of ovulation induction (schedule 1: 15 treatment cycles in 13 women) was compared to a high-dose, individually adjusted "controlled-superovulation" scheme of human menopausal gonadotropin administration (schedule 2: 18 treatment cycles in 17 women, with four women also having been treated under schedule 1). In schedule 2 more human menopausal gonadotropin was employed, 17 beta-estradiol plasma levels were higher, and more ova were retrieved per treatment cycle (p less than 0.01) with a higher rate of mature ova (p = 0.001). Also, under this schedule all treatment cycles resulted in successful retrieval of ova, whereas under schedule 1, four cycles (27%) were abandoned before laparoscopy because the follicles had ovulated (p = 0.03). Furthermore, the proportion of embryos cleaving to the two- to four-cell stage were higher under schedule 2 (38 of 53, or 72%) as compared to schedule 1 (13 of 25, or 52%), but this was not statistically significant (p = 0.07). Two pregnancies were conceived under schedule 2 giving a rate of 11% per treatment cycle. It was concluded that schedule 2, the individually adjusted controlled-superovulation scheme of human menopausal gonadotropin administration, was the superior technique of ovulation induction in an in vitro fertilization program.

Adult↗

Alterations of 20 alpha-hydroxysteroid dehydrogenase activity in cultured rat granulosa cells by follicle-stimulating hormone and testosterone.

The effect of follicle-stimulating hormone (FSH) and testosterone (T) on rat granulosa cell progestin metabolism was investigated by incubation of the cells for 24 h with FSH and/or T and subsequent reincubation with an appropriate rabiolabeled steroid for 3 h. Exposure to varying concentrations of FSH (8-1000 ng/ml) and T (4-500 nM) decreased overall 4-[14C] progesterone utilization and accumulation of 20 alpha-reduced metabolites of progesterone in a dose-related manner. The accumulation of 5 alpha-reduced metabolites was not markedly changed by FSH and T treatments. Treatments with FSH and/or T decreased utilization of all progestins studied: progesterone by 30-50%, 20 alpha-hydroxy-4-pregnen-3-one by 23-31%, 3 alpha-hydroxy-5 alpha-pregnan-20-one by 41-64%, and 5 alpha-pregnane-3 alpha,20 alpha-diol by 26-34%. The greatest effects were observed following FSH + T treatments. Decreased utilization of substrates was associated with the decrease of 20 alpha-hydroxy-steroid dehydrogenase activity; the conversion of progesterone to 20 alpha-hydroxy-4-pregnen-3-one was decreased by 44-62%, the conversion of 20 alpha-hydroxy-4-pregnen-3-one to progesterone was decreased by 41-61%, the conversion of 3 alpha-hydroxy-5 alpha-pregnan-20-one to 5 alpha-pregnane-3 alpha,20 alpha-diol was decreased by 42-69%, and the conversion of 5 alpha-pregnane-3 alpha,20 alpha-diol to 3 alpha-hydroxy-5 alpha-pregnan-20-one was decreased by 53-60%. The incubation of granulosa cells with cyanoketone (10(-6)M), an inhibitor of delta 5,3 beta-hydroxysteroid dehydrogenase, virtually eliminated de novo progesterone production but did not alter the inhibitory effect of FSH and T on radiolabeled progesterone utilization and accumulation of 20 alpha-reduced metabolites, indicating that the observed effects are not influenced by endogenous production of progesterone. It was concluded from these studies that both FSH and testosterone inhibit the 20 alpha-hydroxysteroid dehydrogenase activity and consequently decrease progesterone catabolism by granulosa cells.

20-Hydroxysteroid Dehydrogenases↗

Relief of asthma in two patients receiving danazol for endometriosis.

This paper describes two patients with endometriosis in whom treatment with danazol resulted in a concomitant remission of asthma. Neither patient reported an association of clinical symptoms with phases of their menstrual cycle. Whether the remission was fortuitous or related to suppression of the activity of the endometriotic tissue or to the ability of danazol to increase the serum levels of two protease inhibitors that are deficient in patients with asthma remains to be determined.

Adult↗

Evaluation of the beta-Neocept test for early pregnancy.

We tested the validity of the beta-Neocept test for early pregnancy against that of the plasma human chorionic gonadotropin beta-subunit radioimmunoassay (beta-HCG RIA). The beta-Neocept test had a sensitivity of 88%, a specificity of 93%, a positive predictive value of 95%, a negative predictive value of 84% and an accuracy of 90%. In view of these performance characteristics, its low cost and its ease of use, the beta-Neocept test could be used as the initial pregnancy test when there is a high probability of pregnancy, as there was in this study population, which consisted of 111 women attending endocrine infertility clinics. The more expensive beta-HCG RIA could be reserved for special indications and for patients in whom the results of the urinary hemagglutination inhibition tests are inconsistent with the clinical signs and symptoms.

Adult↗