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)

The objectives were to compare expression of mRNA for cytochrome P450 cholesterol side-chain cleavage (P450scc), cytochrome P450 17alpha-hydroxylase (P450c17), cytochrome P450 aromatase (P450arom), 3beta-hydroxysteroid dehydrogenase Delta(4), Delta(5) isomerase (3beta-HSD), FSH receptor (FSHr) and LH receptor (LHr) in bovine ovarian follicles of the first and second waves of the bovine oestrous cycle and to determine if LH infusion changes growth, steroidogenesis and gene expression in second wave follicles. Transrectal ultrasonography was used to examine follicular size changes during the oestrous cycle in non-lactating Holstein cows (n=31). Saline or purified bovine LH was infused intravenously into cows at emergence of follicular waves for 2 or 4 days using a computer-controlled syringe pump (n=5-6 per treatment). Treatments were: wave 1, saline (W1S); wave 2, saline (W2S) or LH (25 microg/h; W2LH). During infusion, blood samples were collected at 12min intervals for 8h via i.v. catheters for measurement of serum LH concentrations. Ovaries were removed from cows on days 2 or 4 after emergence of follicular waves. Follicles were frozen and stored at -80 degrees C. Follicular fluid (FF, 50 microl) was collected for determination of progesterone (P4), oestradiol-17beta (E2) and androstenedione (A4) concentrations. Frozen sections (14 microm) were used for in situ hybridization to measure expression of mRNA (% pixel intensity) for P450scc, P450c17, P450arom, 3beta-HSD, FSHr, and LHr. LH infusion resulted in a serum LH pattern (high frequency) similar to the early luteal phase. There were no significant differences in size of follicles among the three treatment groups. Follicular fluid concentrations of E2 and A4 in W2S were lower than those of W1S on day 2 of a follicular wave. LH infusion into cows during the midluteal phase increased follicular fluid E2 and A4 concentrations in second wave follicles on day 2 of a follicular wave (W2LH) compared to those of W2S. The increase in follicular fluid E2 on day 2 in wave 2 follicles after LH infusion occurred possibly through an increase in mRNA expression of P450c17 and 3beta-HSD. In conclusion, follicular fluid concentrations of E2 and A4 were lower in W2S than in W1S and E2 and A4 concentrations were restored by infusion of LH in W2LH with an increase in mRNA expression of P450c17 and 3beta-HSD.
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PMID:Concentrations of steroids and expression of messenger RNA for steroidogenic enzymes and gonadotropin receptors in bovine ovarian follicles of first and second waves and changes in second wave follicles after pulsatile LH infusion. 1153 Feb 65

Steroidogenesis is a major function of the developing follicle. However, little is known about the stage of onset of steroid regulatory proteins during follicular development in sheep. In this study, several steroidogenic enzymes were studied by immunohistochemistry and/or in situ hybridization; cytochrome P450 side chain cleavage (P450(scc)), cytochrome P450 17alpha-hydroxylase (17alphaOH), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), cytochrome P450 aromatase (P450(arom)), steroidogenic factor 1 (SF-1), steroidogenic acute regulatory protein (StAR), and LH receptor (LH-R). To define the stages of follicular growth, ovarian maps were drawn from serial sections of ovine ovaries, and follicles were located and classified at specific stages of growth based on morphological criteria. In this way, the precise onset of gene expression with respect to stages of follicular growth for all these proteins could be observed. The key findings were that ovine oocytes express StAR mRNA at all stages of follicular development and that granulosa cells in follicle types 1-3 express 3beta-HSD and SF-1. Furthermore, the onset of expression in theca cells of StAR, P450(scc), 17alphaOH, 3beta-HSD, and LH-R occurred in large type 4 follicles just before antrum formation. This finding suggests that although the theca interna forms from the type 2 stage, it does not become steroidogenically active until later in development. These studies also confirm that granulosa cells of large type 5 follicles express SF-1, StAR, P450(scc), LH-R, and P450(arom) genes. These findings raise new questions regarding the roles of steroidogenic regulatory factors in early follicular development.
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PMID:Onset of steroidogenic enzyme gene expression during ovarian follicular development in sheep. 1190 8

There have been reports of successful follicular growth following xenogenic transplantation of the human ovarian cortex into immunodeficient mice. In this study, we examined the immunohistochemical expression and localization of steroidogenic enzymes in the graft of nonpathological human ovary following xenogenic transplantation into nonobese diabetic severe combined immune deficient (NOD-SCID) mice. We studied human follicles following xenotransplantation into NOD-SCID mice using immunohistochemistry antibodies against the cell proliferation marker (Ki 67), steroidogenic enzymes P450 cholesterol side chain cleavage (P450 scc), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), cytochrome P450 17alpha hydroxylase (P450 c17), cytochrome P450 aromatase (P450 arom), androgen receptor (AR), estrogen receptor (ER), and Ad4-binding protein (Ad4BP), a transcription factor for all steroidogenic P450 genes. In the pre-antral follicles of these grafts, Ki 67 and Ad4BP were detected in both the theca and granulosa cell layer. P450 scc, P450 c17, 3beta-HSD, and AR were present in only the theca cell layer, observations of which were consistent with the findings of nonpathological human ovarian cortex. P450 arom and ER were not detected in these grafts, however, and these follicles did not possess any specific feature of a dominant follicle. These findings suggest that the expression of steroidogenic enzymes in human follicles following xenogenic transplantation into NOD-SCID mice is similar to that of nonpathological human ovaries. However, these follicles do not possess any features of dominant follicles, which are known to develop into the corpus luteum.
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PMID:Immunohistochemical localization of steroidogenic enzymes in human follicle following xenotransplantation of the human ovarian cortex into NOD-SCID mice. 1265 35

Organotins are known to induce imposex (pseudohermaphroditism) in marine neogastropods and are suggested to act as specific endocrine disruptors, inhibiting the enzyme-mediated conversion of steroid hormones. Therefore, we investigated the in vitro effects of triphenyltin (TPT) on human 5alpha-reductase type 2 (5alpha-Re 2), cytochrome P450 aromatase (P450arom), 17beta-hydroxysteroid dehydrogenase type 3 (17beta-HSD 3), 3beta-HSD type 2 and 17beta-HSD type 1 activity. First, the present study demonstrates that significant amounts of TPT occurred in the blood of eight human volunteers (0.17-0.67 microg organotin cation/l, i.e. 0.49-1.92 nmolcation/l). Second, TPT showed variable inhibitory effects on all the enzymes investigated. The mean IC(50) values were 0.95 microM for 5alpha-Re 2 (mean of n=4 experiments), 1.5 microM for P450arom (n=5), 4.0 microM for 3beta-HSD 2 (n=1), 4.2 microM for 17beta-HSD 3 (n=3) and 10.5 microM for 17beta-HSD 1 (n=3). To exclude the possibility that the impacts of TPT are mediated by oxidizing essential thiol residues of the enzymes, the putative compensatory effects of the reducing agent dithioerythritol (DTE) were investigated. Co-incubation with DTE (n=3) resulted in dose-response prevention of the inhibitory effects of 100 microM deleterious TPT concentrations on 17beta-HSD 3 (EC(50) value of 12.9 mM; mean of n=3 experiments), 3beta-HSD 2 (0.90 mM; n=3), P450 arom (0.91 mM; n=3) and 17beta-HSD 1 (0.21 mM; n=3) activity. With these enzymes, the use of 10mM DTE resulted in an at least 80% antagonistic effect, whereas, the effect of TPT on 5alpha-Re 2 was not compensated. In conclusion, the present study shows that TPT acts as an unspecific, but significant inhibitor of human sex steroid hormone metabolism and suggests that the inhibitory effects are mediated by the interaction of TPT with critical cysteine residues of the enzymes.
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PMID:Dithioerythritol (DTE) prevents inhibitory effects of triphenyltin (TPT) on the key enzymes of the human sex steroid hormone metabolism. 1276 82

The medical treatment of endometriosis needs to be optimized. Therapeutic management strategies of endometriosis-associated pain or recurrent disease is primarily aimed at downregulating the ovarian function or at antagonizing the effect of estrogen in ectopic endometrial implants. In this context, basic research is delivering powerful tools for the possible development of new, specific treatment modalities. Recently, aromatase overexpression has been detected in endometriotic tissue. Aromatase (p450arom) is responsible for conversion of C19 androgens to estrogen in several human tissues. Aromatase activity gives rise to local estrogen biosynthesis, which, in turn, stimulates prostaglandin E(2) production by upregulation of cyclooxygenase-2 (COX-2), thus establishing a positive feedback cycle. Another abnormality in endometriosis, i. e. the deficiency in 17 beta-hydroxysteroiddehydrogenase type-II (17 beta-HSD-Type-II) expression, impairs the inactivation of estradiol to estrone. In contrast to the eutopic endometrium, these molecular aberrations collectively favour accumulation of increasing amounts of local estradiol and prostaglandin E(2) in endometriosis. In several human cell lines, prostaglandin and estrogen concentrations are associated with proliferation, migration, angiogenesis, apoptosis resistance, and even invasiveness. Consequently, aromatase and COX-2 are promising new therapeutic targets. In summary, specific aromatase inhibitors (such as Letrozole, Anastrozol or Exemestan) or selective COX-2 inhibitors (e.g. Celecoxib, Rofecoxib) are of great interest to be studied in clinical trials in premenopausal woman with endometriosis to extend the spectrum of currently available treatment options.
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PMID:[Aromatase inhibitors--theoretical concept and present experiences in the treatment of endometriosis]. 1450 58

Gonadotropins (GTHs; FSH and LH) require two major steroidal mediators, estradiol-17 beta (E(2)) and 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (17 alpha,20 beta-DP) to act as critical hormones to execute oocyte growth and maturation, respectively. A two-cell type model has been proposed, where the theca cells provide the precursor steroids, and the granulosa cells produce the two steroidal mediators under the direct influence of FSH and LH. A distinct shift in steroidogenesis, i.e. from E(2) to 17 alpha,20 beta-DP as well as the steroidogenic enzyme genes from ovarian cytochrome P450 aromatase (oP450arom) to 20 beta-hydroxysteroid dehydrogenase (20 beta-HSD), occurs in the granulosa layers of ovarian follicles prior to oocyte maturation. The triggering of the steroidogenic shift by GTHs in granulosa cells occurs through the subjugation of Ad4BP/SF-1 expression in respect of oP450arom, followed by an over-expression of 20 beta-HSD probably through the CREB.
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PMID:A shift in steroidogenesis occurring in ovarian follicles prior to oocyte maturation. 1502 70

Many genes involved in gonadal development have been proposed for mammals. To elucidate if those genes play any critical role in sexual differentiation of the avian gonad, we have examined expressions of the genes for proposed sex-determining factors (SF1, Sox9, DMRT1, Wpkci, and AMH), steroidogenic enzymes (P-450scc, 3beta-HSD, P-450c17, 17beta-HSD and aromatase) and the estrogen receptor in the urogenital system during chicken embryogenesis (days 4-16 of incubation), using a semi-quantitative reverse transcription-polymerase chain reaction. Transcripts of the genes for sex-determining factors except Wpkci and AMH were detected in both sexes but had no sexual dimorphism. Wpkci expression was female specific and constantly high throughout incubation. AMH was expressed in both sexes from the earliest stages but was higher in males than in females after the onset of gonadal differentiation. Expressions of the genes for more downstream enzymes in a steroidogenic pathway, such as P-450c17, 17beta-HSD and aromatase, were clearly higher in females than in males. In particular, 17beta-HSD expression increased in the course of gonadal development in females, whereas it was constantly low in males. Aromatase was highly expressed in females during gonadal differentiation but not in males over the period. In addition, to elucidate the relationship between gene activation during embryogenesis and reproductive abnormalities in wild birds, we examined expressions of these genes in embryos treated with various doses of diethylstilbestrol (DES), as a representative estrogenic compound. DES had no effect on the expressions of all the genes in either sex during the periods of gonadal differentiation (days 8, 12, and 16). Sexual dimorphism of the gene expression for steroidogenic enzymes appeared to be closely related to gonadal development in the chicken embryo, especially in the female. However, all the genes examined here seem unlikely to respond to xenoestrogens.
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PMID:Gene expression of sex-determining factors and steroidogenic enzymes in the chicken embryo: influence of xenoestrogens. 1530 64

The present study was designed (i) to assess the changes in the activity of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and cytochrome P450 aromatase (P450arom) in the ovaries of hens which are subjected to a pause in egg laying by fasting, and (ii) relate these changes with progesterone (P(4)) and estradiol (E(2)) production in the ovary. Hy-Line Brown laying hens (n=90) were fasted for 5 days with water deprivation only on day 3 and subsequently fed every second day up to day 13 and then ad libitum. Birds were euthanized (n=18) on day 0, 3, 6, 9 and 16 of the experiment. The activities of 3beta-HSD and P450arom were evaluated in stroma with cortical follicles (<1mm) and in the wall of white non-hierarchical (1-8 mm) and yellow hierarchical follicles (>8 mm) by histochemical and immunohistochemical method, respectively. Ovarian P(4) and E(2) were measured radioimmunologically. Hens stopped egg laying on day 4 of the experiment and pause in egg laying lasted up to day 12. The hens then began to gradually resume egg laying and on day 16 all hens laid eggs. It was found that during the pause in egg laying: (i) the activity of 3beta-HSD in stroma and normal white follicles was slightly decreased while P450arom activity was significantly increased; (ii) in yellow hierarchical follicles which became atretic and regressed, activity of both enzymes were markedly decreased; (iii) ovarian P(4) production dramatically decreased, whereas ovarian E(2) production after an initial decrease significantly increased. In white atretic follicles the activity of 3beta-HSD and P450arom was very weak during the whole experiment. In conclusion, the present results indicate that during a pause in egg laying white follicles become resistant to atresia.
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PMID:Steroidogenic activity of chicken ovary during pause in egg laying. 1610 May 67

We investigated the effects of theca cells or FSH on granulosa cell differentiation and steroid production during bovine early follicular growth, using a co-culture system in which granulosa and theca cells were cultured on opposite sides of a collagen membrane. Follicular cells were isolated from early antral follicles (2-4 mm) that were assumed to be in gonadotropin-independent phase and just before recruitment into a follicular wave. Granulosa cells were cultured under serum-free conditions with and without theca cells or recombinant human FSH to test their effects on granulosa cell differentiation. Messenger RNA levels for P450 aromatase (aromatase), P450 cholesterol side chain cleavage (P450scc), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), LH receptor (LHr), and steroidogenic acute regulatory protein (StAR) in granulosa cells were measured by real-time quantitative RT-PCR analysis. FSH enhanced aromatase mRNA expression in granulosa cells, but did not alter estradiol production. FSH also enhanced mRNA expression for P450scc, LHr, and StAR in granulosa cells, resulting in an increase in progesterone production. In contrast, theca cells enhanced aromatase mRNA expression in granulosa cells resulting in an increase in estradiol production. Theca cells did not alter progesterone production and mRNA expression in granulosa cells for P450scc, 3beta-HSD, LHr, and StAR. The results of the present study indicate that theca cells are involved in both rate-limiting steps in estrogen production, i.e., androgen substrate production and aromatase regulation, and that theca cell-derived factors regulate estradiol and progesterone production in a way that reflects steroidogenesis during the follicular phase of the estrous cycle.
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PMID:Effects of ovarian theca cells on granulosa cell differentiation during gonadotropin-independent follicular growth in cattle. 1654 62

There is evidence that estrogens can directly modulate human prostate cell activity. It has also been shown that cultured human prostate cancer LNCaP can synthesize the active estrogen estradiol (E2). To elucidate the metabolism of estrogens in the human prostate, we have studied the expression of enzymes involved in the formation and inactivation of estrogens at the cellular level. 17beta-Hydroxysteroid dehydrogenase (17beta-HSD) types 1, 2, 4, 7, and 12, as well as aromatase mRNA and protein expressions, were studied in benign prostatic hyperplasia (BPH) specimens using in situ hybridization and immunohistochemistry. For 17beta-HSD type 4, only in situ hybridization studies were performed. Identical results were obtained with in situ hybridization and immunohistochemistry. All the enzymes studied were shown to be expressed in both epithelial and stromal cells, with the exception of 17beta-HSD types 4 and 7, which were detected only in the epithelial cells. On the basis of our previous results, showing that 3beta-HSD and 17beta-HSD type 5 are expressed in human prostate, and of the present data, it can be concluded that the human prostate expresses all the enzymes involved in the conversion of circulating dehydroepiandrosterone (DHEA) to E2. The local biosynthesis of E2 might be involved in the development and/or progression of prostate pathology such as BPH and prostate cancer through modulation of estrogen receptors, which are also expressed in epithelial and stromal cells.
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PMID:Expression of enzymes involved in estrogen metabolism in human prostate. 1665 92


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