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Biomedical subjects

A J Duleba

Publications and source records attributed to A J Duleba.

At least 37 records · Page 2Linked to original sources
PubMed1995

Baseline cyst formation after luteal phase gonadotropin-releasing hormone agonist administration is linked to poor in vitro fertilization outcome.

OBJECTIVE: To investigate the prognostic significance of baseline ovarian cysts after luteal phase GnRH agonist (GnRH-a) administration for IVF-ET. DESIGN: All nondonor IVF-ET cycles in one program in which luteal phase GnRH-a was administered between July 1993 and January 1994 were assessed for the formation of baseline ovarian cysts defined as a mean diameter > or = 15 mm. Outcome data from the IVF cycles were compared between patients with and without baseline ovarian cysts. RESULTS: Of 78 IVF cycles, baseline cysts > or = 15 mm were noted in 26 cycles. Cycles in which cysts were formed were associated with significantly older patients with significantly higher baseline FSH values. Cycles in which cysts were present demonstrated fewer follicles, retrieved oocytes, and embryos. Cyst cycles also demonstrated a lower peak E2 level, implantation rate, and clinical pregnancy rate (PR) per initiated cycle (7.7% versus 32.7%). Cyst cycles also demonstrated a higher cancellation rate. Logistic regression modeling, accounting for age, confirmed significantly lower clinical PRs in cycles with a baseline cyst. CONCLUSIONS: Baseline cyst formation after luteal phase GnRH-a administration is both a marker for poor responders and a reliable predictor of poor stimulation and low PRs in a given IVF-ET cycle.

Chorionic Gonadotropin↗
PubMed1995

Changes in magnetic resonance transverse relaxation times of two muscles following standardized exercise.

Magnetic resonance (MR) imaging studies of exercising leg muscles were performed to compare the changes in MR transverse relaxation times (T2) that result from exercise of the anterior tibialis (AT) and extensor digitorum/hallicus longus (E) in the anterior compartment of the lower leg with those T2 changes in the medial and lateral gastrocnemius (G) in the posterior compartment. Spin-echo MR images were obtained at 1.5 Tesla before and during the first 14 min of recovery from dynamic exercise. In order to normalize the exercise, workloads for each subject were set at 25% of the measured maximum voluntary contraction (MVC) of the anterior and posterior compartments. In separate exercise sessions, a nonmagnetic, pneumatic exercise apparatus was employed for either dorsiflexion or plantarflexion against a fixed constant resistance for two different exercise durations (1 min 45 s or 5 min). Transaxial MR images (TR = 1000 ms, TE = 30, 60, 90, 120 ms, 128 x 256 matrix, 1.5 cm slice) were used to calculate T2 values. Although subjects performed approximately 7-fold more work (P < or = 0.001, dorsiflexion vs plantarflexion) during plantarflexion than during dorsiflexion at both exercise duration's, the exercise induced T2, while being greater than those at rest (P < or = 0.001), were not significantly different in the different compartments. We conclude that, when exercised at the same workload (25% of MVC), these two muscles produce T2 changes that are not significantly different from each other.

Adult↗
PubMed1993

Sandostatin has no direct effect on ovarian steroidogenesis in vitro.

Rat granulosa and theca-interstitial cells from immature, oestradiol-treated rats were isolated and incubated for 144 h with follicle stimulating hormone (FSH), luteinizing hormone (LH), insulin alone or in combinations, and with two doses of sandostatin (10(-7) M and 10(-6) M per culture). Oestradiol and testosterone production by granulosa and theca-interstitial cells, respectively, was measured in culture media. The stimulatory effects of FSH alone and FSH with insulin but not insulin alone on oestradiol production by granulosa cells were observed. Similarly, increased testosterone concentrations after treatment with LH alone and LH with insulin but not insulin alone were found in media from theca-interstitial cells. The addition of high or low doses of sandostatin to the cultures did not affect the production of oestradiol or testosterone. It was concluded that sandostatin does not exert any direct effect on ovarian steroidogenesis in vitro.

Animals↗
PubMed1993

Insulin actions on ovarian steroidogenesis are not modulated by metformin.

Metformin, an agent used in treatment of non-insulin-dependent diabetes mellitus, is believed to act by potentiating the effects of insulin on glucose metabolism. This study was designed to determine whether metformin affects the actions of insulin on ovarian steroidogenic capability. Rat thecal-interstitial (T-I) and granulosa (G) cells were cultured in chemically defined media for 144 h with or without gonadotrophins [luteinizing hormone (LH) at 100 ng/ml or follicle stimulating hormone (FSH) at 100 ng/ml], insulin (1 microgram/ml) and/or metformin (1 and 5 micrograms/ml). Production of testosterone and progesterone by T-I cells, and 17 beta-oestradiol and progesterone by G cells were assessed. Insulin potentiated LH-dependent stimulation of testosterone production by T-I cells and FSH-dependent stimulation of 17 beta-oestradiol production by G cells, but did not significantly affect progesterone production by T-I cells or G cells in the presence or absence of gonadotrophins. Metformin did not affect any of the actions of insulin on steroidogenesis. These results suggest that insulin may modulate ovarian steroidogenesis via a pathway separate from that modulating glucose metabolism. Actions of insulin on steroidogenesis are selective with regard to stimulation of specific aspects of steroidogenesis and do not simply amplify gonadotrophin effects.

Animals↗
PubMed1992

Expectant management of choriocarcinoma limited to placenta.

Choriocarcinoma limited to placenta was discovered "incidentally" following a seemingly uneventful term pregnancy. The newborn had unsuspected severe anemia and thrombocytopenia, due to fetomaternal hemorrhage. His recovery was good following transfusions. The mother was asymptomatic and her extensive workup for metastatic choriocarcinoma was negative. She was subsequently managed expectantly and monitored with serial serum beta-hCG, demonstrating near-logarithmic decline to non-pregnant levels within 5 weeks of delivery.

Adult↗
PubMed1992

Prognostic factors in assessment and management of male infertility.

Evaluation of 304 infertile couples with at least one abnormal semen analysis (sperm density < 20 x 10(6)/ml and/or motility < 50%) and no apparent female factors was performed in a multicentre prospective cohort study. In 73 cases therapeutic donor insemination was performed (TDI group) with a resulting pregnancy rate of 48%. The remaining 231 couples (non-TDI group) had an overall pregnancy rate of 25%. The TDI group had a shorter duration of infertility. The ages of both partners were comparable in TDI and non-TDI groups. In the non-TDI group, univariate analysis resulted in identification of six clinical variables associated with a change in pregnancy rates. The strongest association was noted for length of infertility. There was a weaker association for semen volume, concentration of leukocytes in semen, history of pregnancy in the female partner and laparoscopy. Multiple variable analysis of data from the non-TDI group revealed that independent predictors of pregnancy were 'duration of infertility' and 'history of pregnancy in the female partner'. The multiple variable modelling suggested that (i) an increase in the length of infertility by 1 month prolongs the time to pregnancy by an additional 1.6% (95% confidence interval: 1.5-1.7%); and (ii) a history of past pregnancy in the female partner reduces the time of pregnancy by 51% (95% confidence interval: 47-56%).

Female↗
PubMed1989

Effects of clomiphene citrate on ovarian function in hypophysectomized rats.

On Days 28-30 of age, hypophysectomized rats were treated with oestradiol-17 beta (0.1 mg/day) and/or clomiphene citrate (0.1 mg/day). Subsequent treatment with PMSG (10 i.u., on Day 31) and hCG (10 i.u., on Day 33) was identical for all animals. Rats were killed on Day 34. Treatment with oestradiol-17 beta alone resulted in ovulations of 45.1 +/- 5.5 oocytes/rat (mean +/- s.e.m.). There were no ovulations among animals treated with clomiphene citrate alone but treatment with oestradiol-17 beta and clomiphene citrate resulted in a significant (P less than 0.05) reduction (23.1 +/- 7.6 oocytes/rat) in ovulatory response. Similarly, ovarian weights and serum progesterone concentrations were highest in the oestradiol-17 beta-treated rats, intermediate in those given oestradiol plus clomiphene citrate and the lowest in rats receiving clomiphene citrate alone. We suggest that clomiphene citrate exerts direct ovarian antiovulatory and oestrogen-antagonist actions.

Animals↗
PubMed1988

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↗
PubMed1987

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↗
PubMed1986

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↗
PubMed1986

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↗
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

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

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

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↗