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Biomedical subjects

Y S Moon

Publications and source records attributed to Y S Moon.

At least 73 records · Page 4Linked to original sources
PubMed1985

Effects of cannabinoids on progesterone release in cultures of rat luteal cells.

This study investigated the direct effects of tetrahydrocannabinols (THC) on progesterone release by cultured rat luteal cells, as a function of dose and time. During a 24-h incubation, the level of progesterone in the culture medium was decreased by 35% and 60% in the presence of 1 microM 11-OH-delta 9-THC and 8 beta-OH-delta 9-THC, respectively, when compared with control cultures. Dose-response analysis revealed that 8 beta-OH-delta 9-THC inhibited progesterone levels at 0.1 microM but not at lower concentrations. The action of 8 beta-OH-delta 9-THC was rapid in onset and a significant effect could be observed as early as 2 h following the addition of the cannabinoid. While luteinizing hormone (LH, 1 microgram/ml) significantly enhanced progesterone release in the culture medium over the respective control levels, this action of LH was dramatically suppressed by the concomitant presence of 8 beta-OH-delta 9-THC at 2, 4 and 24 h in separate experiments. Moreover, the increase in the level of progesterone in the culture medium induced by 8-bromo-cyclic AMP was also attenuated by the concomitant presence of 8 beta-OH-delta 9-THC in the cultures. These results further substantiate a direct action of cannabinoids on the steroidogenic function of the corpus luteum, and that it involves at least some step(s) distal to the LH-sensitive adenylate cyclase system.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

Inhibition of 20 alpha-hydroxysteroid dehydrogenase activity by follicle-stimulating hormone and androgens in cultured rat granulosa cells: a search for the mechanism of action.

Alterations of progesterone metabolism and especially of 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD) activity were studied in cultured rat granulosa cells following various treatments. The cells were incubated for up to 48 h with or without follicle-stimulating hormone (FSH), androgens, hydroxyflutamide, estrogens, chlorea toxin, and dibutyryl cAMP [Bu2 cAMP]. Subsequently, the cells were incubated for 3 h with [4-14 C] progesterone (0.5 microM). The progesterone utilization and accumulation of 20 alpha-reduced and 5 alpha-reduced metabolites were assessed following thin-layer chromatography separation of radiolabeled steroids. Both FSH (1 microgram/ml) and testosterone (0.5 microM) decreased the 20 alpha-HSD activity by decreasing the maximal velocity (by 52% and 37%, respectively) without changing significantly the Km value. The inhibition of 20 alpha-HSD was demonstrable following 12 and 24 h exposure to FSH and following 24 and 48 h exposure to testosterone. Effects comparable to that induced by testosterone were elicited by other androgens (androstenedione and 5 alpha-dihydrotestosterone), but not by estrogens (estradiol-17 beta and estrone). Hydroxyflutamide reversed testosterone-induced effects: the increase of endogenous progesterone accumulation and the decrease of 20 alpha-HSD activity. Both cholera toxin (0.001-10 micrograms/ml) and Bu2 cAMP (62.5-1000 micrograms/ml) caused a dose-dependent inhibition of 20 alpha-HSD activity. Present results indicate that: the inhibition of 20 alpha-HSD by both FSH and androgens may be of a noncompetitive nature; androgen action on 20 alpha-HSD may be a true androgenic, receptor-mediated effect; and cAMP may mediate the FSH action on 20 alpha-HSD activity.

20-Hydroxysteroid Dehydrogenases↗
PubMed1984

Differential actions of FSH and androgens on progesterone catabolism by rat granulosa cells.

Rat granulosa cells were preincubated with follicle-stimulating hormone (FSH, 1 micrograms/ml) and/or androgens (testosterone and 5 alpha-dihydrotestosterone, 0.5 microM) and subsequent [4-14C]progesterone metabolism by these cells was studied. Granulosa cells metabolized radiolabeled progesterone to three major products 20 alpha-hydroxy-4-pregnen-3-one, 3 alpha-hydroxy-5 alpha-pregnan-20-one, and 5 alpha-pregnane-3 alpha, 20 alpha-diol. Androgens, but not FSH, decreased overall progesterone utilization. Both FSH and androgens decreased conversion of progesterone to 20 alpha-hydroxy-4-pregnen-3-one. The accumulation of 5 alpha-pregnane-3 alpha, 20 alpha-diol was increased by FSH, decreased by testosterone, and not altered by 5 alpha-dihydrotestosterone. The accumulation of 3 alpha-hydroxy-5 alpha-pregnan-20-one was significantly increased by both FSH and androgens. Present results indicate that FSH as well as androgens modulate progesterone metabolism by rat granulosa cells. FSH appears to increase 5 alpha-reductase activity and/or decrease 20 alpha-hydroxysteroid dehydrogenase activity while androgens decrease only 20 alpha-hydroxysteroid dehydrogenase activity.

Animals↗
PubMed1984

Clinical, endocrinologic, and intraovarian prostaglandin F responses to H-1 receptor blockade in the ovarian hyperstimulation syndrome: studies in the rabbit model.

The effects of chlorpheniramine maleate, an H-1 receptor blocker, on clinical and endocrinologic features and intraovarian prostaglandin F (PGF) content were assessed in the rabbit model of the ovarian hyperstimulation syndrome. H-1 receptor blockade prevented ascites, attenuated ovarian enlargement (2.68 +/- 0.37 gm versus 4.15 +/- 0.056 gm; p less than 0.05), and augmented intraovarian PGF content (8.4 +/- 0.84 versus 3.95 +/- 1.12 pg/mg protein; p less than 0.05). Steroidogenesis was unaffected. In the control group, in which weights remained stable, animals with minimal ascites (scores less than or equal to 2; n = 4) were compared to other control animals with a greater accumulation of fluid (scores greater than or equal to 3; n = 4). The former also exhibited lower ovarian weights (2.94 +/- 0.41 versus 5.35 +/- 0.59 gm; p less than 0.05) and higher PGF ovarian content (6.05 +/- 1.56 versus 1.8 +/- 0.75 pg/mg of protein; p less than 0.05). This triad of minimal ascites, lower ovarian weights, and elevated intraovarian PGF seen both in treated animals and in inherently more resistant control animals did not appear to depend on changes in body weight. The conclusion reached was that H-1 receptor blockade prevented ascites, reduced ovarian enlargement, and augmented PGF content but did not affect steroidogenesis. This protective effect of chlorpheniramine may be mediated at least in part by prostaglandins.

Animals↗
PubMed1984

Steroidogenic capabilities of various compartments of rat ovarian follicles in culture.

The production of progesterone, estrogen and androgen as well as the metabolism of radiolabelled progesterone by various cellular components of rat ovarian follicles were studied. Granulosa (G), theca (T), recombined granulosa plus theca (G+T) and intact follicular wall (FW) of ovaries from immature rats treated with pregnant mare serum gonadotropin (8 IU) were cultured for 24 h in the presence or absence of [4-14C]progesterone. The estrogen and androgen accumulation when calculated per follicle was several fold greater in FW than in G, T, or G+T preparations. The conversion of radiolabelled progesterone to its identified C21 catabolites (20 alpha-hydroxy-4-pregnen-3-one and 3 alpha-hydroxy-5 alpha-pregnan-20-one) was significantly lower in FW than in G+T incubations. Conversely, the metabolism of radiolabelled progesterone to androsterone was several fold greater in FW than in G+T incubations. Addition of hydroxyflutamide to FW incubations significantly decreased estrogen production and increased the conversion of radiolabelled progesterone to androsterone. Estrogen production by follicular wall may be enhanced by androgenic stimulation of aromatase activity as well as by a structure-dependent factor(s) of a yet unknown nature, both of which may decrease progesterone catabolism to biologically inactive progestins while promoting progesterone conversion to androgens and eventually to estrogens.

Androgens↗
PubMed1983

The role of prostaglandin F in the symptoms of endometriosis.

Prostaglandin F (PGF) levels in endometriotic tissue in vitro have been shown to be higher than the levels in healthy ovarian tissue and uterine endometrium. The results of a study of nine women with endometriosis support this finding and suggest that prostaglandins have an important role in the pathogenesis of the symptoms and infertility in such women.

Endometritis↗
PubMed1983

Androgenic alteration in pathways of C19-steroid metabolism by cultured rat granulosa cells.

Pretreatment of rat granulosa cells with androgens altered the subsequent metabolism of [4-14C]testosterone in vitro. In cells pretreated with testosterone or 5 alpha-dihydrotestosterone, the accumulation of radiolabeled 5 alpha-androstane-3 alpha, 17 beta-diol decreased by 40% and 36%, respectively, when compared with control, while the levels of androstenedione increased by 64% and 54%, respectively. For comparison, pretreatment with 0.5 microM 17 beta-estradiol failed to affect the level of radioactivity incorporated into all three major metabolites. In other experiments, granulosa cells were incubated in the presence of 0.5 microM [4-14C]dihydrotestosterone. While 5 alpha-androstane-3 alpha, 17 beta-diol was decreased slightly by pretreatment with testosterone or 5 alpha-dihydrotestosterone, radiolabeled androsterone was increased significantly. These data suggest a possible modulatory action of androgens on ovarian 17 beta-hydroxysteroid dehydrogenase and/or 5 alpha-reductase activity.

Androgens↗
PubMed1983

Effect of prolactin in an experimental model of the ovarian hyperstimulation syndrome.

In the rabbit model of the ovarian hyperstimulation syndrome, animals given ovine prolactin with human menopausal gonadotropins (hMGs), as compared to animals receiving hMGs alone, demonstrated an increase in the formation of ascitic fluid, a decrease in mean plasma estradiol, and an increase in the mean plasma progesterone concentrations. The ovarian estradiol and progesterone content reflected that of the peripheral blood. These data suggest that, under the conditions of these experiments, prolactin may play a role in the pathogenesis of ascites formation but not the ovarian enlargement observed in this syndrome. Although the plasma estradiol levels were lower and the progesterone levels were higher in the animals treated with prolactin and gonadotropins, this did not prevent the occurrence of ascites, a cardinal clinical sign of this gonadotropin-induced syndrome.

Animals↗
PubMed1983

Adrenal and sex steroid hormone production by a virilizing adrenal adenoma and its diagnosis with computerized tomography.

The presence of an androgen-secreting tumor in a 29-year-old woman was confirmed and its location was determined by computerized axial tomographic (CAT) scanning. The hormone production from this virilizing adrenal adenoma was studied in vivo and in vitro. The major secretory products of the tumor (as compared to normal adrenal tissue) were testosterone (24-fold) and 17 beta-estradiol (five-fold). Although the adenoma produced lesser amounts of dehydroepiandrosterone sulfate (DHEAS), the demonstration of elevated serum testosterone and DHEAS in serial samples was a better marker for an androgen-secreting adrenal tumor than were the urinary 17-ketosteroids, which remained in the upper limit of normal. The hormone production from the tumor depended neither on adrenocorticotropic hormone nor on human chorionic gonadotropin. The conclusions were that: (1) on the basis of serial measurements of serum testosterone and DHEAS, virilizing adrenal adenomas may be suspected when the concentrations of these hormones reach or exceed 200 ng/dl and 6,600 ng/ml, respectively; (2) the high-resolution CAT scanner can accurately localize these tumors; (3) cosmetic and menstrual dysfunction regressed after resection of the tumor; and (4) virilizing adrenal adenomas may produce both androgens and estrogens.

17-Ketosteroids↗
PubMed1983

Androgenic modulation of progesterone metabolism by rat granulosa cells in culture.

Effects of androgens on progesterone accumulation, utilization of exogenous progesterone and accumulation of [4-14C]progesterone metabolites by rat granulosa cells in culture were studied. Androgen increased progesterone accumulation in cultures without exogenous progesterone and slowed the overall decline of progesterone concentration in cultures supplemented with exogenous progesterone. Both aromatizable testosterone and nonaromatizable 5 alpha-dihydrotestosterone decreased [4-14C]progesterone utilization by granulosa cells by 12 to 30%. This effect was observed irrespective of whether the cells were continuously exposed to androgens or only pre-exposed. In he same experiments, androgens decreased conversion of radiolabeled progesterone to 20 alpha-hydroxy-4-pregnen-3-one by 11 to 50% and to 5 alpha-pregnane-3 alpha, 20 alpha-diol by 26 to 49%. Accumulation of 3 alpha-hydroxy-5 alpha-pregnan-20-one was not altered in 3 h incubations and was increased by up to 43% in 24 h incubations by androgen treatment. It is suggested that androgens alter progesterone catabolism by granulosa cells by decreasing 20 alpha-hydroxysteroid dehydrogenase activity and that this effect may contribute to overall stimulatory action of androgens on progesterone accumulation.

Animals↗
PubMed1982

Enzyme inactivation and inhibition by gossypol.

Three lactate dehydrogenase isozymes and malate dehydrogenase purified from mouse tissues were inactivated with time by low concentration of gossypol. The degree of enzyme inactivation is both gossypol- and enzyme-concentration-dependent. Under the same experimental conditions, lactate dehydrogenase-X and lactate dehydrogenase-5 were inactivated faster than lactate dehydrogenase-1. NADH was shown to partially protect the enzymes against inactivation by gossypol. The results of this study suggest that the enzymes are inactivated by the minor components in gossypol preparations. Isozymes of glutathione S-transferases were reversibly inhibited by gossypol. The inhibition of transferases by gossypol was shown to be competitive with respect to the 1-chloro-2,4-dinitrobenzene. It is proposed that the male antifertility effect of gossypol may be related to the selective inactivation of sperm-specific lactate dehydrogenase-X.

Animals↗
PubMed1982

Metabolism of testosterone by human granulosa cells in culture: influence of follicle-stimulating hormone and luteinizing hormone.

Human granulosa cells were isolated from follicles (8 to 15 mm) and cultivated for 24 hours in the presence or absence of follicle-stimulating hormone (NIH-FSH-HS-1, 1 microgram/ml) and luteinizing hormone (NIAMDD-hLH-1, 1 microgram/ml). Testosterone -4-14C was added subsequently to all cultures for 4-, 6-, and 24-hour periods. Of the seven metabolites of testosterone studied, 17 beta-estradiol (E2) and estrone (E1) were the major products. In all patients, levels of E2 were three to ten times higher than those of E1. Production of E2, but not E1, was stimulated by either follicle-stimulating hormone (FSH) or luteinizing hormone (LH). The cells of the largest follicle (15 mm) showed greater response to LH than to FSH. Production of the other C19 and C18 metabolites was very low or negligible. These results further suggest that FSH regulates the aromatization of testosterone in human granulosa cells, and that LH may have the same effect on the matured follicle during the preovulatory period.

Adult↗
PubMed1982

Comparative studies of androgen metabolism in theca and granulosa cells of human follicles in vitro.

In eight separate experiments, theca and granulosa were isolated from human follicles (5-25 mm in diameter), and their capacities to metabolize radiolabelled testosterone in 24 hour cultures were assessed. Theca metabolized testosterone primarily to androstenedione, however significant aromatization to estradiol-17 beta and to estrone was also observed. Granulosa metabolized testosterone primarily to estra-diol-17 beta and estrone, while smaller quantities were converted to androstenedione. In seven of these experiments, the intermediate of aromatization, 19-hydroxytestosterone, was identified. In six of these experiments, theca, when compared to granulosa, produced more androstenedione but less estradiol-17 beta and estrone. 5 alpha-Reduced androgens were non-detectable or produced in small quantities. In a single experiment, metabolism of androstenedione was compared to metabolism of testosterone by both theca and granulosa. Theca metabolized androstenedione to testosterone in smaller quantities than testosterone to androstenedione. Granulosa metabolized androstenedione to testosterone in higher quantities than testosterone to androstenedione. Both theca and granulosa aromatized androstenedione more readily than testosterone.

Adult↗
PubMed1982

Estradiol-17 beta and androgen secretion by isolated porcine ovarian follicular cells in vitro.

The cellular sources and gonadotropic regulation of porcine ovarian estrogen and androgen were assessed by culturing isolated granulosa cells and thecal cells from medium size follicles (4-6 mm diameter) separately for 24 h in a chemically defined medium containing gonadotropins and (or) testosterone. At the end of the culture period, estradiol-17 beta (estradiol) and androgens in the media were determined by radioimmunoassays. Production of estradiol by granulosa cells without an exogenous aromatizable androgen was low in the absence or presence of a highly purified preparation of either follicle-stimulating hormone (FSH. 0.25 microgram/mL) or luteinizing hormone (LH. 1 microgram/mL). Addition of testosterone or androstenedione (0.5 microM), but not dihydrotestosterone or pregnenolone, significantly increased estradiol secretion. Additional increases were observed when FSH, LH, prostaglandin E2, or dibutyryl cyclic 3'.5'-adenosine monophosphate was present. Production of estradiol by thecal cells was low in the presence or absence of exogenous testosterone, and was essentially unaffected by the presence of gonadotropins. Thecal cells, however, released large amounts of androstenedione and smaller amounts of testosterone and other androgens during 24-h culture and the production of these androgens was stimulated by LH but not by FSH. Androgen secretion by granulosa cells was negligible when compared with the theca and was unaffected by gonadotropins. It is concluded that the theca is the prime site for follicular androgen biosynthesis by the porcine ovarian follicle, and, upon LH stimulation, may provide androgen precursors for estradiol production by granulosa cells.

Androgens↗