Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.1.1.3 (HSD)
 3,464 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The in vivo influence of gonadotropins on the activities of oxidoreductases of androst-5-ane and androst-5-ene steroids and pregnenolone was examined in testes from young rats. Animals were given daily injections of human CG for 5 days starting at 20 days of age and the testicular 12,000 X g supernatants were assayed for steroid oxidoreductase activities. Marked increases (up to 8-fold) were noted in the rate of oxidation of the 3beta-hydroxyl of 3beta-hydroxy-5beta-androstan-17-one, 3 beta-hydroxy-5alpha-androstan-17-one, 5alpha-androstane-3beta,17beta-diol, dehydroepiandrosterone, and pregnenolone, and in the 3-keto reduction of 17beta-hydroxy-5alpha-androstan-3-one, 17beta-hydroxy-5beta-androstan-3-one, 5beta-androstane-3,17-dione, and 5alpha-androstane-3,17-dione. The hormone response required a certain amount of time as no response was detected until 72 h after the first injection. As little as 1 IU hCG/injection resulted in significant increases in 3beta-oxidoreductase (3beta-HSD) activities. FSH and TSH gave no significant increases and 25 microgram NIH-LH-S18 resulted in increases only when the hormone was suspended in a sesame oil-beeswax mixture. Hormone treatments did not result in increased 5-ane-3alpha-HSD activities. Rats receiving chronic human CG treatment starting at 66 days of age showed less marked increases in 5-ane-3beta-HSD activities than the younger rats and no significant enhancement in 5-ene-3beta-HSDs. It is suggested that during sexual maturation the testicular biosynthesis of active 5-ane androgen(s) proceeds via 5-ane precursors with the help of age and gonadotropin-dependent 5-ane 3beta-oxidoreductase.
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PMID:Steroidogenesis in rat Leydig cells: effect of gonadotropins on the activity of 5-ane and 5-ene 3alpha- and 3beta-hydroxysteroid dehydrogenases during sexual maturation. 74 93

Adult male rats were given s.c. injections of melatonin (400 micrograms/100 g body weight per day) for 14 days. On day 15, the weights of the testis and accessory sex organs were less, testicular 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activity was inhibited, spermatogenesis was suppressed and serum levels of gonadotrophins, testosterone and alpha 2u-globulin were decreased compared with control animals injected with vehicle. In a third group of rats given the same dose of melatonin for 14 days, administration of dihydrotestosterone (DHT) at a dose of 25 micrograms/100 g body weight per day on days 8-14 resulted in serum levels of alpha 2u-globulin, FSH, LH and testosterone and testicular 17 beta-HSD activity similar to those seen in vehicle-injected control animals. Weights of the testes and accessory sex organs and spermatogenesis were normal after administration of DHT in melatonin-treated rats. In another group of rats, the depressive effects of melatonin treatment on plasma gonadotrophins were reversed by the administration of alpha 2u-globulin on days 8-14. It was concluded that treatment with DHT prevents the depressive action of melatonin on testicular function by inducing the synthesis of alpha 2u-globulin.
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PMID:Effect of dihydrotestosterone on serum concentrations of alpha 2u-globulin and on spermatogenesis in melatonin-treated rats. 169 6

Quantitative evaluation of the different varieties of germ cells at stage VII of the seminiferous epithelium cycle, namely type-A spermatogonia (ASg), preleptotene spermatocytes (pLSc), midpachytene spermatocytes (mPSc) and step 7 spermatids (7 Sd) along with Leydig cell nuclear area (LCNA) and radioimmunoassay of plasma levels of gonadotropins (FSH and LH), prolactin (PRL) and testosterone (T), activities of testicular, delta 5-3 beta hydroxysteroid dehydrogenase (delta 5-3 beta-HSD) and 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) were measured in mature rats of the Wistar strain following treatment with lithium chloride at a dose of 200 ug/100 g body wt/day for 7,14 and 21 days. A remarkable reduction in plasma levels of FSH (P less than 0.001), LH (P less than 0.05, P less than 0.01), PRL (P less than 0.05, P less than 0.001) and T (P less than 0.001) along with significant diminution in the activities of testicular delta 5-3 beta-HSD (P less than 0.001) and 17 beta-HSD (P less than 0.001) were observed following lithium treatment for 14 and 21 days. 21 days of treatment also resulted a marked degree of degeneration of ASg (P less than 0.05) and 7Sd(P less than 0.001) at stage VII but 14 days of treatment did not exhibited any significant effect on testicular gametogenesis. LCNA was decreased after lithium chloride treatment for 14 and 21 days (P less than 0.001). 7 days of treatment did not exert any notable result in the above parameters. The results of our experiment suggest that duration of lithium treatment is the critical factor for its adverse effects on testicular activity when the plasma levels of lithium remain within the therapeutic range. The possibility of an indirect action of lithium at the level of the testes is also discussed. Hence the data of our experiments have potential clinical implication.
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PMID:Effect of lithium chloride on spermatogenesis and testicular steroidogenesis in mature albino rats: duration dependent response. 184 58

The development of long term culture conditions with which to study the regulation of expression of aromatase, cholesterol side-chain cleavage enzyme, and 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) in human granulosa-lutein cells is described in this report. Conditions have been established for the dispersal, growth, freezing, and storage of functional human granulosa cells isolated from preovulatory follicles of women undergoing laparoscopy for gamete intrafallopian tube transfer and in vitro fertilization procedures. Optimal growth conditions for human granulosa-lutein cells were determined by plating cells at a low density and testing the capacity of a variety of culture conditions to support growth. A combination of fetal bovine serum (FBS), horse serum, and the serum substitute UltroSer G was found to increase cell number to maximal levels, 8- to 10-fold higher than with sera alone. Human granulosa-lutein cells grown under these conditions had a doubling rate of 36-40 h and were morphologically distinct from human theca interna cells grown under similar conditions. Human granulosa-lutein cells treated with forskolin retracted and rounded up, whereas cultures of human ovarian theca interna cells or human fibroblasts treated similarly did not retract. Human granulosa-lutein cells were grown for successive passages and transferred to serum-free medium containing forskolin, LH, hCG, or cholera toxin. Addition of these agents resulted in a time- and dose-dependent increase in aromatase activity and progesterone secretion. In these studies FSH treatment was found not to increase aromatase activity. In a study of the time course of 3 beta HSD activity in the absence of forskolin under serum-free conditions, it was found that 3 beta HSD activity increased 3-fold during the 72-h treatment period. Forskolin-stimulated 3 beta HSD activity also increased in a time-dependent manner, with levels in treated cells 3-fold higher than those in control cells. Northern analysis performed on total RNA obtained from forskolin- or hCG-stimulated granulosa-lutein cells confirmed that the increase in aromatase activity was associated with a corresponding increase in levels of mRNA specific for aromatase cytochrome P-450. Levels of mRNA encoding cholesterol side-chain cleavage cytochrome P-450 were similarly increased in cells treated with forskolin compared with unstimulated values at each of the time points investigated. Under serum-free conditions in the absence of stimulation, the 3.4-kilobase band of aromatase cytochrome P-450 mRNA was detectable.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Proliferating human granulosa-lutein cells in long term monolayer culture: expression of aromatase, cholesterol side-chain cleavage, and 3 beta-hydroxysteroid dehydrogenase. 237 Feb 96

The gonadotrophic regulation of progesterone production by rat granulosa cells was examined in a chemically-defined medium containing FSH, dibutyryl cyclic AMP [Bu)2cAMP) and the calcium ionophore, A23187. FSH and A23187 alone significantly enhanced the production of pregnenolone, progesterone and its metabolite, 20 alpha-hydroxypregn-4-en-3-one (20 alpha-OH-P) from endogenous substrate(s). Stimulation of progesterone production by A23187 was accompanied by an increase in 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) but not 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD) activity, as attested by enhancement of the metabolism of exogenous pregnenolone to progesterone but not of progesterone to 20 alpha-OH-P. In contrast, although (Bu)2cAMP increased pregnenolone and progesterone production and the metabolism of exogenous progesterone to 20 alpha-OH-P, it failed to stimulate the conversion of exogenous pregnenolone to progesterone. The increase in progesterone production and in the conversion of exogenous pregnenolone to progesterone by FSH and A23187 was concentration- and time-dependent. Whereas maximal stimulation of de-novo progesterone synthesis by FSH was evident by 6 h (earliest time examined), a significant increase in the conversion of exogenous pregnenolone to progesterone in the presence of FSH or the ionophore was not noted until 12 h of incubation. Although a small but significant increase in progesterone production was also noted as early as 6 h of incubation in the presence of the calcium ionophore, this was markedly smaller than that elicited by FSH. We conclude that the calcium ionophore A23187 and (Bu)2cAMP have similar as well as distinct effects on progesterone production in rat granulosa cells in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of A23187 and dibutyryl cyclic AMP on progestagen production by rat granulosa cells in vitro. 254 59

Recently, a protein fraction [follicle regulatory protein (FRP)] which inhibits FSH-induced granulosa cell aromatase activity was isolated from both human and porcine follicular fluid. In this study, the actions of FRP on 3 beta-hydroxysteroid dehydrogenase (3 beta-HSDH) activity were examined using granulosa cells obtained from hyperstimulated patients undergoing oocyte aspiration for in vitro fertilization. Granulosa cells were cultured with 0, 167, or 500 micrograms/ml FRP with or without human menopausal gonadotropin (hMG; 10 mIU/ml). After 48 h, the medium (S) was removed and stored. Cells then were mechanically lysed and centrifuged at 10,000 X g. The supernatant was further centrifuged (100,000 X g) to obtain a microsomal fraction (M) and cytosol (C). The M fraction was resuspended in medium 199 with 10(-6) M pregnenolone plus 5 microM NAD+ and incubated for 2 h to determine 3 beta-o1 dehydrogenase activity. The S, C, and M fractions were all assayed for progesterone (P) by RIA. hMG markedly increased P concentrations in the S and C fractions. The M fraction demonstrated a hMG-dependent enhancement in 3 beta-HSDH activity. However, the hMG-associated S, C, and M P levels were decreased in granulosa cells coincubated with FRP. In conclusion, ovarian steroidogenesis may be dependent on the integrated interactions of both gonadotropins and local nonsteroidal paracrine/autocrine modulators of granulosa cell function.
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PMID:Effect of human menopausal gonadotropin and follicle regulatory protein(s) on 3 beta-hydroxysteroid dehydrogenase in human granulosa cells. 392 17

Progestins have recently been shown to augment gonadotropin-stimulated progesterone and 20 alpha-hydroxypregn-4-en-3-one (20 alpha-OH-P) biosynthesis in cultured rat granulosa cells. The mechanism by which progestins autoregulate ovarian progestin biosynthesis was investigated by studying the modulation of pregnenolone biosynthesis as well as the activities of the enzymes 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) and 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD). Granulosa cells obtained from immature hypophysectomized, estrogen-treated rats were cultured with FSH and/or progestins. Pregnenolone production was measured in the presence of cyanoketone (10(-6) M) to inhibit 3 beta-HSD activity. Enzymatic activities of 3 beta-HSD and 20 alpha-HSD were determined in cell homogenates by direct enzyme assays. FSH stimulated pregnenolone production, while treatment with progesterone or R5020 alone was ineffective. Concomitant treatment with the progestins further enhanced FSH-stimulated pregnenolone production in a dose-dependent manner with minimal effective doses of 10(-8) and 10(-7) M for R5020 and progesterone, respectively. In FSH-primed cells, LH increased pregnenolone accumulation, and concomitant treatment with R5020 also enhanced the LH action. Furthermore, the gonadotropins stimulated the activity of 3 beta-HSD, and this effect was further enhanced by concomitant treatment with either R5020 or progesterone in a dose-dependent manner. In addition, the 20 alpha-HSD activities were enhanced by progestins in cells treated with FSH but not with LH. Thus, both natural and synthetic progestins stimulate the gonadotropin-induced progesterone production in cultured granulosa cells via enhancing the 3 beta-HSD enzyme as well as pregnenolone biosynthesis.
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PMID:Progestin regulation of progesterone biosynthetic enzymes in cultured rat granulosa cells. 393 85

Studies within the Arab population in Israel revealed 25 pseudohermaphrodites due to 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) deficiency. Twenty-three individuals, presently living in the Gaza strip, belong to a very large inbred kinship which extends over 8 generations. All affected subjects (46, XY) were born with mild to moderate degrees of ambiguity of an apparently normal-looking female genitalia and therefore were reared as girls. In childhood, genital abnormalities consisted of a clitoral-like phallus surrounded by a chordee, non-fused labial-scrotal folds and a urogenital sinus. The testes were in the inguinal canals, or rarely, in the labial-scrotal folds. Wolffian structures were normally differentiated while Mullerian structures were absent. At puberty, subjects developed a male body habitus with abundant body hair and beard. Gynecomastia was absent. The phallus and testes enlarged to adult proportions while the prostate remained small. Together with the physical change from girls to boys they developed a male identity having erections and ejaculations, which in 7 cases led to the spontaneous adoption of a male gender role. In adults the hormonal abnormalities consisted of greatly elevated delta 4-androstenedione (delta 4) (350-1267 ng/dl) associated with subnormal testosterone (T) levels (0.9-3.1 ng/ml). Dihydrotestosterone (DHT) levels, with the exception of 1 patient, were relatively low in all cases (27-35 ng/dl). Children had low levels of delta 4, T and DHT, which were normal for age. Although from puberty on there was a significant rise of the 3 androgens, delta 4 always remained extremely elevated and T and DHT relatively low when compared to normal controls. Dexamethasone failed to suppress the androgen pattern while HCG augmented the defect, making the diagnosis possible in 2 prepubertal children. Dehydroepiandrosterone (DHEA) and 17-hydroxyprogesterone (17-OHP) levels were normal or moderately elevated. Estradiol (E2) levels were normal in children and all but 2 adults, who had high levels. LH and FSH levels were very high after puberty, but normal before. However, there was an overresponse to LHRH in all age groups. The contrast between the lack of intrauterine virilization of the external genitalia in fetuses with 17 beta-HSD deficiency versus the marked masculinization that occurs after puberty still remains a puzzling phenomenon. It is conceivable that the postpubertal development of a male phenotype with change of gender identity and role occurs due to the joint effect of delta 4, T and DHT, even though secreted in inadequate proportions. Thus masculinization in these individuals is a slow process requiring a longer period of time than that of normal puberty to be completed.
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PMID:Male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase deficiency: studies on the natural history of the defect and effect of androgens on gender role. 631 Feb 48

This study presents the first evidence that the non-hormonal, biological substance, 1,2,3- trihydroxypropane (THP) acts as a selective and potent antispermatogenic agent without any apparent toxic or endocrine side effects. The studies were done on 119 rats which were injected intratesticularly (50-200 microliter) with either sterile filtered distilled water (Control) or water/THP (3:7; Treated) and histological, biochemical and fertility determinations were made up to 11 weeks after the injections. The results show that within one week of a single injection with THP, the weights of testes and epididymides are significantly less than those of the Controls and the reduced weights persist for at least 11 weeks. The seminiferous tubules are largely depleted of spermatogenetic cells by 2 weeks and they remain devoid of dividing germ cells for the 11 week period. The Leydig cells have a normal appearance and histochemically show the same 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) and 3 beta-HSD activities as Controls. In vitro studies of the testes showed that the activities of the steroid enzymes 20 alpha-HSD, 17 beta-HSD, 17 alpha-hydroxylase and C17-20-lyase and the production of testosterone and androstenedione were not altered by the THP treatment. Similarly, serum levels of testosterone, LH, and FSH, measured by RIA, and weights of the prostate and seminal vesicles were the same as in Controls. Treated males showed the same degree of sexual behaviour and mating frequency as the Controls, but after the 3rd mating were 100% infertile for the duration of the experiments. The total number of sperm in epididymides of Treated rats was reduced by 99.99% after the 3rd mating.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Suppression of spermatogenesis without inhibition of steroidogenesis by a 1,2,3-trihydroxypropane solution. 642 45

The mechanism by which gonadotropin-releasing hormone (GnRH) inhibits ovarian progesterone production was investigated by studying the GnRH modulation of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD)/delta 5-delta 4-isomerase activity in cultured rat granulosa cells. Ovarian granulosa cells, obtained from immature hypophysectomized estrogen-treated rats, were incubated with various hormones in vitro, and 3 beta-HSD activity was determined by measuring the conversion of radiolabeled pregnenolone to progesterone. Treatment with FSH increased the apparent maximal velocity of the enzyme by about 6-fold in a dose-dependent manner, with an ED50 value of 3.58 ng/ml. FSH treatment also resulted in an approximately 10-fold increase in the apparent Km of this enzyme (from 0.46 to 4.98 microM). In contrast, concomitant treatment with GnRH (10(-8) M) inhibited the FSH-stimulated increase in enzyme activity by about 27%. This inhibitory effect of GnRH was associated with a decrease in the apparent maximal velocity, while the apparent Km remained unchanged. Furthermore, the inhibitory effect of GnRH was observed whether the enzyme activity was expressed per mg protein or per mg DNA. Concomitant treatment with 10(-6) M of a GnRH antagonist, [D-pGlu1,D-Phe2,D-Trp3,6]GnRH, completely blocked the inhibitory effect of GnRH. In contrast to the inhibitory effect of GnRH on FSH-stimulated 3 beta-HSD activity, treatment with GnRH alone increased enzyme activity by about 40%. This was accompanied by a slight but significant stimulation of basal progestin production by GnRH in granulosa cells. The present results coupled with the observed GnRH stimulation of 20 alpha-HSD activity reported earlier suggest that GnRH inhibits the FSH stimulation of progesterone production by decreasing the conversion of pregnenolone to progesterone as well as by increasing the metabolism of progesterone.
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PMID:Regulation of ovarian 3 beta-hydroxysteroid dehydrogenase activity by gonadotropin-releasing hormone and follicle-stimulating hormone in cultured rat granulosa cells. 680 8


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