Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

In gonadectomized rats of either sex s.c. administration of 5 alpha-dihydrotestosterone (DHT) reversed, in a dose dependent manner, effects brought about by gonadectomy: it decreased pituitary wet weight and serum levels of LH and FSH and suppressed microsomal enzyme activities involved in testosterone and progesterone metabolism in the pituitary gland, NADPH-linked 5 alpha-reductase and NADH-linked 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSDH). Concomitantly administered nonsteroidal antiandrogen, flutamide (5 mg/day), antagonized some of the suppressive effects induced by a 14-day treatment of gonadectomized rats with high dose (1 mg/day) of DHT. It completely blocked DHT action on pituitary 5 alpha-reductase activity in the female rat and, in the male, inhibition was found to be 30-35%. In male, but not female rats, it completely blocked DHT suppression of serum FSH level whereas it slightly, but significantly inhibited DHT suppression of serum LH in rats of either sex. However, flutamide did not prevent DHT suppression of pituitary wet weight or NADH-linked 3 alpha-HSDH activity. Concomitantly administered progestational antiandrogen, cyproterone acetate (5 mg/day), inhibited DHT-induced weight increase of seminal vesicles by 50-55% and completely blocked the weight decrease of pituitary gland but did not antagonize DHT suppression of serum gonadotropins or pituitary enzyme activities. The results obtained with flutamide suggest that DHT-induced suppression of pituitary NADPH-linked 5 alpha-reductase, but not NADH-linked 3 alpha-HSDH activity, might involve an androgen receptor mechanism.
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PMID:The action of 5 alpha-dihydrotestosterone and antiandrogens on the activities of 5 alpha-reductase and 3 alpha-hydroxysteroid dehydrogenase in the pituitary gland of gonadectomized rats. 680 44

The influence of androgens on the FSH modulation of progestin biosynthetic enzymes was studied in vitro. Granulosa cells obtained from immature, hypophysectomized, estrogen-treated rats were cultured for 3 days in a serum-free medium containing FSH (20 ng/ml) with or without increasing concentrations (10(-9)-10(-6)M) or 17 beta-hydroxy-5 alpha-androstan-3-one (dihydrotestosterone; DHT), 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-diol), or the synthetic androgen 17 beta-hydroxy-17-methyl-4,9,11-estratrien-3-one (methyltrienolone; R1881). FSH treatment increased progesterone and 20 alpha-hydroxy-4-pregnen-3-one (20 alpha-OH-P) production by 10.2- and 11-fold, respectively. Concurrent androgen treatment augmented FSH-stimulated progesterone and 20 alpha-OH-P production in a dose-related manner (R1881 greater than 3 alpha-diol greater than DHT). In the presence of an inhibitor of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), the FSH-stimulated pregnenolone (3 beta-hydroxy-5-pregnen-20-one) production (a 20-fold increase) was further enhanced by co-treatment with R1881, 3 alpha-diol or DHT. Furthermore, FSH treatment increased 4.4-fold the activity of 3 beta-HSD, which converts pregnenolone to progesterone. This stimulatory action of FSH was further augmented by concurrent androgen treatment. In contrast, androgen treatment did not affect FSH-stimulated activity of a progesterone breakdown enzyme, 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD). These results demonstrate that the augmenting effect of androgens upon FSH-stimulated progesterone biosynthesis is not due to changes in the conversion of progesterone to 20 alpha-OH-P, but involves an enhancing action upon 3 beta-HSD/delta 5,delta 4-isomerase complexes and additional enzymes prior to pregnenolone biosynthesis.
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PMID:Androgen regulation of progestin biosynthetic enzymes in FSH-treated rat granulosa cells in vitro. 682 Dec 86

Activin is a dimeric protein implicated in the local control of follicular steroidogenesis. Using cultured rat granulosa cells, we previously showed that the effect of activin on FSH-induced progesterone synthesis changes with preovulatory follicular development, from positive regulation in nondifferentiated (immature) granulosa cells to negative regulation in preovulatory (mature) granulosa cells. The aim of the present study was to assess development-related effects of activin on the expression of enzymes crucial to progesterone synthesis: cholesterol side-chain cleavage cytochrome P450 (P450scc) and 3 beta-hydroxysteroid dehydrogenase/delta 5-4-isomerase (3 beta HSD). Nondifferentiated granulosa cells were isolated from the ovaries of estrogen-pretreated immature female rats that received no other treatment; differentiated granulosa cells were obtained from similar animals treated for 48 h with human FSH to induce preovulatory follicular development. Cells were cultured for 48 h in serum-free medium with and without human FSH and/or recombinant activin-A, and medium was collected for measurement of progestagens (progesterone, pregnenolone, and 20 alpha-dihydroprogesterone). In cultures of nondifferentiated granulosa cells, activin augmented the FSH-induced production of all three steroids. In differentiated granulosa cells, activin suppressed the FSH-stimulated production of progesterone and 20 alpha-dihydroprogesterone, but had no effect on pregnenolone. The presence of exogenous pregnenolone increased the overall production of progesterone, but did not alter qualitative steroidogenic responses to activin. To assess the interaction between FSH and activin on 3 beta HSD and P450scc messenger RNA (mRNA) expression, Northern blot analyses were performed on total RNA isolated from cultured granulosa cells. Treatment in vitro with FSH alone markedly enhanced the abundance of both the 3 beta HSD and P450scc mRNA transcripts in nondifferentiated and differentiated granulosa cells. FSH-stimulated expression of P450scc mRNA was further enhanced by cotreatment of nondifferentiated granulosa cells with activin. However, activin had no consistent effect on FSH-stimulated expression of 3 beta HSD mRNA in nondifferentiated cells. In differentiated granulosa cells, both mRNAs were suppressed more than 50% by the presence of activin. We conclude that the in vitro effects of activin on FSH-induced expression of 3 beta HSD and P450scc mRNAs in rat GC are similar: initially stimulatory (P450scc) or without effect (3 beta HSD), then becoming completely inhibitory. The mechanism of this development-dependent change in the granulosa cell response to activin remains to be elucidated.
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PMID:Regulation of 3 beta-hydroxysteroid dehydrogenase delta 5/delta 4-isomerase and cholesterol side-chain cleavage cytochrome P450 by activin in rat granulosa cells. 762 57

The expression of four major steroidogenic enzymes in porcine theca and granulosa cell layers of preovulatory follicles was related to the levels of steroids in follicular fluid and gonadotropin concentrations in peripheral serum at slaughter. Ovaries were collected during proestrus, early estrus, and late estrus as evidenced by behavioral signs. Follicles were dissected from the ovaries, and theca, granulosa, and follicular fluids were pooled for each of 24 sows. Cytochromes P450 17 alpha-hydroxylase/17-20 lyase (P450c17), aromatase (P450arom) and side-chain cleavage (P450scc), as well as 3 beta-hydroxysteroid dehydrogenase (3 beta HSD), were subjected to Northern and Western immunoblot analyses. The concentrations of estradiol-17 beta, testosterone, androstenedione, and progesterone were determined in follicular fluid, and peripheral serum was assayed for estradiol-17 beta, LH, and FSH. Stages of preovulatory development were verified by plasma levels of LH, FSH, and estradiol-17 beta. Thecca expressed P450c17, P450arom, P450scc, and 3 beta HSD whereas granulosa expressed only P450arom and low levels of P450scc. Thecal P450c17, thecal P450arom, and granulosa P450arom expression decreased coincidentally as serum estradiol-17 beta and follicular fluid estradiol-17 beta, testosterone, and androstenedione levels declined after the presumed gonadotropin surge. Unlike P450c17 and P450arom P450scc and 3 beta HSD remained relatively constant in theca and granulosa. From these data, we suggest that the theca interna may be the primary steroidogenic compartment of the porcine follicle during its final stages of preovulatory development. Moreover, preovulatory estrogen secretion appears to be controlled by the coordinated expression of a triad of enzymes in the porcine follicle that includes theca P450c17, theca P450arom and granulosa P450arom.
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PMID:Steroidogenesis in the preovulatory porcine follicle. 781 46

The effects of prostatectomy on testicular steroidogenic enzymes, and on serum levels of gonadotropins, prolactin, and testosterone were studied. Adult male rats were prostatectomized and sacrificed after 14 and 21 days. There was augmentation of both delta 5-3 beta-hydroxysteroid dehydrogenase (delta 5-3 beta-HSD) and 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activities in the testes along with increased levels of FSH, prolactin, and testosterone in the serum, while no changes were observed in serum levels of LH. Hence it may be concluded that the prostate gland has an inhibitory effect on testicular androgenesis and can exert some influence in the regulation of FSH and prolactin secretion.
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PMID:Effects of prostatectomy on testicular androgenesis and serum levels of gonadotropins in mature albino rats. 784 63

The relationship between glucocorticoid secretion from the adrenal gland and gonadal function has previously been attributed to central inhibition by the adrenal steroids of pituitary gonadotropin output. This review focuses on the direct actions of glucocorticoids within the gonads, including positive effects on germ cell maturation and both positive and negative effects on the stimulation of gonadal steroidogenesis by LH and FSH. In addition, we address the role in the gonads of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD), which interconverts the glucocorticoids with their inactive 11-ketosteroid derivatives. To date, two isoforms of 11 beta HSD have been described. 11 beta HSD1, purified and cloned from the liver, has a relatively low affinity for glucocorticoids and acts instead as an 11-oxoreductase, whereas the high affinity 11 beta HSD2, first identified in the kidney, acts as an efficient 11 beta-dehydrogenase to inactivate physiological concentrations of glucocorticoid. We propose that in the gonads, 11 beta HSD1 promotes the positive effects of glucocorticoids on germ cell maturation (by increasing the local concentration of active glucocorticoids), whereas a high affinity 11 beta-dehydrogenase activity, consistent with that of 11 beta HSD2, inactivates glucocorticoids and so protects luteal cells from the inhibitory effects of these steroids during the luteal phase of the ovarian cycle.
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PMID:A working hypothesis for the regulation of steroidogenesis and germ cell development in the gonads by glucocorticoids and 11 beta-hydroxysteroid dehydrogenase (11 beta HSD). 805 59

We report pubertal maturation and dynamic studies of gonadotropin and gonadal hormone secretion in long term glucocorticoid-treated siblings with nonsalt-wasting classic adrenal and gonadal 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) deficiency. The 18-yr-old female siblings spontaneously developed thelarche and menarche at 10 and 12 yr, respectively, and manifested irregular menses, hirsutism, and polycystic ovaries at 17 yr. The 16-yr-old male sibling spontaneously developed secondary sex characteristics at age 11 yr and exhibited Tanner IV-V pubic hair, a 6.5 x 3.0-cm surgically repaired penis, and enlarged nonnodular testes. Overnight (2200-0700 h) plasma gonadotropin (every 20 min) and gonadal steroid levels (every 2 h) under ACTH adrenal suppression revealed the following. In the male sibling, there were overall normal Tanner V male LH (3-21 mIU/mL) and FSH (1.2-13 mIU/mL) levels, normal peak frequency and amplitude of LH (70 +/- 62 min and 15 +/- 3 mIU/mL, respectively) and FSH (65 +/- 28 min and 13 +/- 3 mIU/mL), and low normal Tanner V testosterone (T) levels (11.4-17.9 nmol/L). In the female sibling, there were normal follicular phase range LH (10-28 mIU/mL) and FSH (5.1-17.2 mIU/mL) levels, normal peak frequency and amplitude of LH (96 +/- 17 min and 22 +/- 4.5 mIU/mL, respectively) and FSH (62 +/- 27 min, 13 +/- 4 mIU/mL), and early follicular phase estradiol (E2) levels (100-170 pmol/L). The LH-releasing hormone-stimulated LH response was in the normal adult range in the male and normal for the early follicular phase in the female. In contrast, ACTH and adrenal delta 5-steroid responses to CRH administration were elevated in each sibling. Gonadal suppression via Norlutin administration (30 mg/day for 3 days) after prolonged adrenal suppression by dexamethasone resulted in suppression of dehydroepiandrosterone (DHEA) and E2 in the female and DHEA and T in the male. Gonadal stimulation via hCG administration (5000 IU/day for 3 days, im) during continuous adrenal suppression resulted in a low E2 response in the female (200 pmol/L; control, 295-660 pmol/L) and a low T response in the male (15.3 nmol/L; control, 17-39 nmol/L), whereas delta 5-17-hydroxypregnenolone and DHEA levels rose 2- to 4.7-fold in each sibling. In conclusion, despite partial gonadal 3 beta HSD deficiency, the dynamics of gonadotropin and gonadal hormone secretion in these siblings indicate the absence of increased LH secretion, in contrast to the markedly increased ACTH secretion resulting from adrenal 3 beta HSD deficiency.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Hypothalamic-pituitary-gonadal axis function in pubertal male and female siblings with glucocorticoid-treated nonsalt-wasting 3 beta-hydroxysteroid dehydrogenase deficiency congenital adrenal hyperplasia. 807 18

The effects of gonadotropins (LH + FSH) and dexamethasone on the spermatogenic and steroidogenic activity in the adrenalectomized Mabuya carinata have been studied. Secondary spermatocytes, spermatids, and spermatozoa were absent, and there was a significant decrease in the activity levels of delta 5-3 beta-hydroxysteroid dehydrogenase (delta 5-3 beta-HSDH) and glucose-6-phosphate dehydrogenase in the adrenalectomized lizards compared with those of controls. Administration of either dexamethasone or LH + FSH to adrenalectomized lizards resulted in restoration of testicular activity as revealed by the appearance of secondary spermatocytes, spermatids, and spermatozoa and a significant increase in the activity level of delta 5-3 beta-HSDH compared to that of adrenalectomized lizards. The results indicate that impairment in gonadotropin secretion might be a major factor in inducing testicular regression following adrenalectomy in M. carinata.
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PMID:Effects of dexamethasone and gonadotropins on the testis of the adrenalectomized lizard Mabuya carinata (Schn.) 817 28

Activin and inhibin are structurally related dimeric glycoproteins belonging to the transforming growth factor-beta superfamily of proteins which are synthesized and secreted by the granulosa cells of the ovary. Although initially characterized by their ability to influence FSH secretion from pituitary cells, paracrine regulatory roles of these factors on neighboring ovarian theca interna have been suggested. While inhibin has been shown to increase and activin to decrease the production of androgens, the mechanisms of action are not well defined, partly due to difficulties in obtaining adequate numbers of thecal cells from individual patients or animal models. Using a unique human ovarian thecal-like tumor (HOTT) cell culture model system we investigated the biochemical and molecular mechanisms controlling C19 steroidogenesis and the effects of activin and inhibin on the activity and expression of key ovarian thecal steroidogenic enzymes, cholesterol side-chain cleavage cytochrome P450 (P450scc), 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) and 17 alpha-hydroxylase/17,20 lyase cytochrome P450 (P450c17). Steroid production, level of steroidogenic enzyme mRNA expression, and enzyme activity following treatment with forskolin, inhibin-A and activin-A were examined. Basal steroid production, enzyme activities, and steroidogenic enzyme mRNA levels were not markedly different following treatment with activin (25 ng/ml) or inhibin (25 ng/ml) alone. Forskolin (10 microM) markedly increased production of both androstenedione (fivefold) and progesterone (threefold) as well as the activity of 3 beta HSD (sevenfold), and P450c17 (sevenfold) over basal. Forskolin stimulated the expression of mRNA for P450scc (fourfold), 3 beta HSD (threefold), and P450c17 (eightfold) over basal. Androstenedione accumulation was decreased by 60% in the forskolin plus activin group compared with forskolin alone, while progesterone production was maintained. This was attributed to a reduction of P450c17 mRNA (45% of forskolin alone) and activity (45% of forskolin alone). In contrast, co-treatment with forskolin and inhibin increased androstenedione production by 40% while decreasing progesterone by 40% compared with forskolin alone. Concomitantly, this was associated with a higher P450c17 mRNA expression (1.5-fold) and activity (twofold) but with minimal effects on the mRNA for 3 beta HSD and P450scc. HOTT cell responses to activin (0.05-50 ng/ml) and inhibin (0.05-50 ng/ml) in the presence of forskolin demonstrated dose-dependent effects on the steroid accumulation, enzymatic activity and mRNA expression of P450c17. Additionally, the differences seen on mRNA expression of steroidogenic enzymes in response to these factors were time-dependent. In summary, forskolin stimulated C19 steroid production from HOTT cells by increasing the expression of all steroidogenic enzymes examined. Inhibin and activin exerted differential effects on the expression of these enzymes which resulted in alterations in the steroid profile toward production of C19 steroids in the case of inhibin and away from C19 steroids in the case of activin. The influence of these important intraovarian factors on the expression of P450c17, a pivotal enzyme in thecal cell production of C19 steroids, could impact greatly on the follicular milieu of a normal developing follicle as well as in pathophysiological disorders such as polycystic ovarian syndrome.
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PMID:Inhibin and activin differentially regulate androgen production and 17 alpha-hydroxylase expression in human ovarian thecal-like tumor cells. 869 35

The distributions of oxytocin (OT) and the oxytocin receptor (OTR) have been characterised in preovulatory follicles of the marmoset monkey and are described in relation to the process of luteinisation using a combination of in vitro and in vivo techniques, including immunohistochemistry and granulosa cell culture. Ovaries were collected in the periovulatory phase before and 22h after exogenous gonadotropin (hCG) treatment, but prior to ovulation. Before hCG treatment, OT immunoreactivity (OT-ir) was found mostly in granulosa cells of antral follicles, especially in the layers nearest the antrum. In contrast, oxytocin receptor immunoreactivity (OTR-ir) was observed principally in basal granulosa cells of antral follicles. Progesterone receptor (PR) and 3 beta hydroxysteroid dehydrogenase (3 beta HSD), markers for luteinisation, were negative for all ovarian tissues collected before hCG treatment. After hCG treatment, almost all granulosa cell layers in antral follicles stained positively for both OT-ir and OTR-ir, most prominently in preovulatory follicles and especially in the cumulus oophorus. This increase in staining was associated with an induction of PR and 3 beta HSD activity in the granulosa cells of preovulatory follicles. OT production by granulosa cells in culture was stimulated by the addition of hCG, but only in cultures derived from preovulatory follicles; whereas FSH was without any effect. Addition of extrinsic OT to the cultures elicited an increase in progesterone production only for the granulosa cells derived from preovulatory follicles. Together, the results of the in vivo and in vitro studies point to an involvement of OT in the process of leuteinisation in the marmoset monkey.
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PMID:Oxytocin: a follicular luteinisation factor in the marmoset monkey. 871 8


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