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 cellular localization of inhibin alpha, betaA, and betaB subunits, 3beta-hydroxysteroid dehydrogenase (3beta-HSD), and cytochrome P450 aromatase (aromatase) in stallion testes was investigated. In addition, detailed seasonal changes in circulating immunoreactive (ir)-inhibin were investigated in correlation with testosterone, estradiol, LH, and FSH. Inhibin alpha subunit-positive staining was observed in Sertoli cells, and more clearly positive staining was noted in Leydig cells. Inhibin betaA and betaB subunits were also stained in both types of cells. Immunoreactivity of 3beta-HSD and aromatase was confined to the Leydig cells. There was no seasonal effect on the percentage of the areas within seminiferous tubules and interstitial tissues that stained positive for the inhibin alpha subunit. The highest plasma concentrations of ir-inhibin were observed in the breeding season, and the lowest levels were noted during the nonbreeding season. The circulating concentrations of ir-inhibin, steroid hormones, and gonadotropins were positively correlated with each other throughout the 2 years studied. The presence of the inhibin alpha and beta subunits in Leydig cells and Sertoli cells in the equine testis suggests that these cells may secrete dimetric (bioactive) inhibin in circulation of stallions, and that the circulating ir-inhibin may be a useful indicator of the testicular function of stallions.
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PMID:Testicular inhibin in the stallion: cellular source and seasonal changes in its secretion. 967 94

In human estrogen-dependent neoplasms such as breast, endometrioid endometrial, and surface epithelial-stromal ovarian carcinomas, intratumoral aromatase is considered to play important roles in converting circulating androgens derived from adrenal cortex and/or ovary to estrogens, possibly in association with 17 beta-HSD type 1 and estrogen sulfatase. Analysis of intratumoral aromatase in these estrogen-dependent neoplasms is important not only in understanding the development and biological behavior of these tumors, but also in the clinical management of these patients, because suppression of intratumoral aromatase by newly developed aromatase inhibitors may provide new potentials in endocrine therapy of these patients.
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PMID:Intratumoral aromatase in human breast, endometrial, and ovarian malignancies. 979 59

Troglitazone (a thiazolidinedione that improves insulin resistance) lowers elevated androgen concentrations in women with polycystic ovarian syndrome. In this study, we assessed the direct effects of troglitazone on steroidogenesis in porcine granulosa cells. Troglitazone inhibited progesterone production in a dose- and time-dependent manner (earliest effects at 4 h, maximum at 24 h) without affecting cell viability. Progesterone production was also inhibited by troglitazone in the presence of 25-hydroxycholesterol, indicating that the drug does not affect intracellular cholesterol transport. Troglitazone also inhibited FSH- and forskolin-stimulated progesterone secretion. The reduced progesterone production was accompanied by marked elevations of pregnenolone concentrations, suggesting inhibition of 3beta-hydroxysteroid dehydrogenase (3beta-HSD). The activity of 3beta-HSD in troglitazone-treated granulosa cells was decreased by more than 60%, compared with controls after 24 h. Troglitazone did not affect aromatase activity in porcine granulosa cells. In summary, troglitazone has direct effects on porcine granulosa cell steroidogenesis. The drug specifically inhibits 3beta-HSD activity, resulting in impaired progesterone production. The clinical relevance of this direct in vitro effect on steroidogenesis needs further investigation.
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PMID:Troglitazone inhibits progesterone production in porcine granulosa cells. 983 34

Sex steroids play a crucial role in the development and differentiation of normal mammary gland as well as in the regulation of breast cancer growth. Local intracrine formation of sex steroids from inactive precursors secreted by the adrenals, namely, dehydroepiandrosterone and its sulfate, may regulate growth and function of peripheral target tissues, including the breast. Both endocrine and paracrine influences on the proliferation of human breast cancer cells are well recognized. Breast tumors harbor tumor-associated macrophages and tumor-infiltrating lymphocytes that secrete a wide spectrum of cytokines. These factors may also contribute to neoplastic cell activity. The present study was designed to investigate the action of cytokines on 3beta-hydroxysteroid dehydrogenase (3beta-HSD) activity, which is an essential step in the biosynthesis of active estrogens and androgens in human breast cancer cell lines and in normal human mammary epithelial cells in primary culture. 3Beta-HSD activity was undetectable in ZR-75-1 and T-47D estrogen receptor-positive (ER)+ cells under basal growth conditions. This activity was markedly induced after exposure to picomolar concentrations of interleukin (IL)-4 or IL-13. The potent stimulatory effect of these cytokines on 3beta-HSD activity was also observed in the ER- MDA-MB-231 human breast cancer cell line and in normal human mammary epithelial cells (HMECs) in primary culture. The stimulation of 3beta-HSD activity by IL-4 and IL-13 results from a rapid increase in 3beta-HSD type 1 mRNA levels as measured by RT-PCR and Northern blot analyses. Such an induction of the 3beta-HSD activity may modulate androgenic and estrogenic biological responses as demonstrated using ZR-75-1 cells transfected with androgen- or estrogen-sensitive reporter constructs and treated with the adrenal steroid 5-androstene-3beta,17beta-diol. The DNA-binding activity of Stat6, a member of the signal transducers and activators of transcription gene family, is activated 30 min after exposure to IL-4 and IL-13 in human breast cancer cell lines as well as in HMECs in primary culture. In these cells, Stat6 activated by IL-4 or IL-13 binds to two regions of the 3beta-HSD type 1 gene promoter, containing Stat6 consensus sequences. IL-4 induction of 3beta-HSD mRNA and activity is sensitive to staurosporine. This protein kinase inhibitor also inhibits IL-4-induced Stat6 DNA-binding activity. Our data demonstrate for the first time that IL-4 and IL-13 induce 3beta-HSD type 1 gene expression, thus suggesting their involvement in the fine control of sex steroid biosynthesis from adrenal steroid precursors in normal and tumoral human mammary cells. Furthermore, aromatase and/or 5alpha-reductase(s) are expressed in the mammary gland and in a large proportion of human breast tumors. An increase in the formation of their substrates, namely, 4-androstenedione and testosterone, may well have a significant impact on the synthesis of active estrogens and androgens in these tissues.
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PMID:Induction of 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase type 1 gene transcription in human breast cancer cell lines and in normal mammary epithelial cells by interleukin-4 and interleukin-13. 989 13

Ovarian interstitial cells (OICs) are a common feature of mammalian gonads but little is understood concerning their origin or functional significance. This study investigated the development and steroidogenic potential of OIC in feral and colony-reared feline queens. Reproductive tracts, collected from a total of 50 female colony and feral cats, were fixed and analyzed by morphometry. Ovarian sections were also immuno-stained for the expression of the steroidogenic enzymes 17alpha-hydroxylase/17,20 lyase cytochrome P450 (P450c17), 3beta-hydroxysteroid dehydrogenase/Delta5-Delta4 isomerase (3beta-HSD), and aromatase. These findings were related to serum estradiol and testosterone concentrations and to the degree of existing cystic endometrial hyperplasia (CEH). Feral cats had three times as many OICs as colony-reared queens (2713 +/- 855 vs 744 +/- 494 cells/mm(2), P < 0.01). These cells were lipid laden and expressed both P450c17 and 3beta-HSD at levels that were higher than those seen in the theca interna of adjacent follicles. Aromatase expression was undetectable. The pattern of enzyme expression was consistent with development of interstitial tissue from atretic follicles and the potential for continued steroid secretion during the anestrum. The incidence of CEH was higher in older (>5 years old; 88.2%) than in younger (2-4 years; 30%) colony queens (P < 0. 01), whereas no such disease was evident in any of the feral cats. Estradiol levels were higher in colony-reared than in feral cats, but testosterone levels were not different. These data are consistent with the transformation of the theca interna of atretic follicles in cats into OICs that retain a similar, or even enhanced, steroidogenic phenotype. Colony-reared cats exhibit a predisposition to CEH compared with feral queens that is associated with elevated serum estradiol concentrations. Whether or not OICs somehow prevent the development of uterine disease or otherwise reflect a gonadal response to reduced negative feedback on the hypothalamic-pituitary axis remains to be determined.
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PMID:Studies on the origin of ovarian interstitial tissue and the incidence of endometrial hyperplasia in domestic and feral cats. 1052 57

Enzymes modulating local steroid availability play an important role in the progression of human breast cancer. These include isoforms of 17beta-hydroxysteroid dehydrogenase (17-HSD), aromatase and steroid sulphatase (STS). The aim of this study was to investigate the expression, by reverse transcription polymerase chain reaction, of 17-HSD types I-IV, aromatase and steroid STS in a series of 51 human breast tumour biopsies and 22 primary cultures of epithelial and stromal cells derived from these tumours, giving a profile of the steroid-regulating network for individual tumours. Correlations between enzyme expression profiles and expression of the interleukin (IL)-6 gene were also sought. All except one tumour expressed at least one isoform of 17-HSD, either alone or in combination with aromatase and STS. Expression of 17-HSD isoforms I-IV were observed in nine tumours. Of the 15 tumours which expressed three isoforms, a combination of 17-HSD II, III and IV was most common (6/15 samples). The majority of tumours (n = 17) expressed two isoforms of 17-HSD with combinations of 17-HSD II and IV predominant (7/17 samples). Eight tumours expressed a single isoform and of these, 17-HSD I was in the majority (5/8 samples). In primary epithelial cultures, enzyme expression was ranked: HSD I (86%) > STS (77%) > HSD II (59%) > HSD IV (50%) = aromatase (50%) > HSD III (32%). Incidence of enzyme expression was generally reduced in stromal cultures which were ranked: HSD I (68%) > STS (67%) > aromatase (48%) > HSD II (43%) > HSD IV (28%) > HSD III (19%). Expression of IL-6 was associated with tumours that expressed > or = 3 steroid-converting enzymes. These tumours were of higher grade and tended to come from patients with family history of breast cancer. In conclusion, we propose that these enzymes work in tandem with cytokines thereby providing sufficient quantities of bioactive oestrogen from less active precursors which stimulates tumour growth.
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PMID:In vivo and in vitro expression of steroid-converting enzymes in human breast tumours: associations with interleukin-6. 1057 57

Although progesterone plays an essential role in ovulation and the luteiniziation of the primate follicle, the expression of cellular components required for progesterone synthesis and their control is not well defined. This study was designed to determine the time course and gonadotrophin versus steroid regulation of the transcription of genes involved in progesterone synthesis in peri-ovulatory follicles. Granulosa cells or whole ovaries were obtained from macaques undergoing controlled ovarian stimulation either before (0 h) or up to 36 h following the administration of an ovulatory human chorionic gonadotrophin (HCG) bolus with or without a 3beta-hydroxysteroid dehydrogenase (3beta-HSD) inhibitor, with or without a non-metabolizable progestin. Granulosa cell concentrations of low density lipoprotein receptor (LDL-R) and steroidogenic acute regulatory protein (StAR) mRNA increased transiently 12 h following HCG administration (P < 0.05) at which time steroid depletion tended to reduce StAR mRNA (P = 0.06). At 36 h post-HCG progesterone suppressed the LDL-R mRNA levels (P < 0.05). P450 side-chain cleavage (P450scc) mRNA decreased in a time-dependent fashion up to 24 h, whereas 3beta-HSD mRNA increased within 12 h of HCG administration (P < 0.05) in a steroid-independent manner. Whole ovarian 17alpha-hydroxylase (P450c17) and granulosa cell P450 aromatase (P450arom) mRNA declined in a time-dependent fashion; by 36 h after HCG administration, steroid depletion increased P450arom mRNA, although progestin replacement did not return aromatase to control values (P < 0.05). These data demonstrate diverse patterns of steroidogenic enzyme expression that generally reflect the conversion of the macaque peri-ovulatory follicle from an oestrogen to progesterone producing gland. Although mRNAs associated with progesterone synthesis and metabolism are primarily regulated by gonadotrophins, cholesterol uptake and utilization may be modulated locally by steroids in luteinizing granulosa cells.
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PMID:Hormonal regulation of steroidogenic enzyme expression in granulosa cells during the peri-ovulatory interval in monkeys. 1061 Dec 55

In contrast to normal endometrium, the expression of aromatase is aberrant in endometriosis and is stimulated by prostaglandin E2 (PGE2). This results in local production of estrogen, which induces PGE2 formation and establishes a positive feedback cycle. Another abnormality in endometriosis--deficient 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) type 2 expression--impairs the inactivation of estradiol (E2) to estrone (E1). These molecular aberrations collectively favor accumulation of increasing quantities of E2, and PGE2 in endometriosis. The clinical relevance of these findings was exemplified by the successful treatment of an unusually aggressive case of postmenopausal endometriosis with an aromatase inhibitor.
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PMID:Aromatase as a therapeutic target in endometriosis. 1065 2

In the course of avian embryo development, estrogen has been indicated to play a key role in gonadal differentiation by the inhibition of aromatase (P-450arom) that synthesizes estrogen from androgen. Biosynthesis of estrogen requires not only P-450arom but also other enzymes for a steroidogenic pathway. To elucidate gonadal differentiation, the steroidogenic pathway should be studied comprehensively in the early developmental stages including that of sex differentiation. Therefore, in the present study, the expressions of the steroidogenic genes, P-450scc, 3beta-HSD, P-450c17, 17beta-HSD and P-450arom, were measured at the developmental stages (days 2-9 of incubation) of chicken embryos by quantitative RT-PCR. Transcripts for all the genes studied, except for P-450arom were detected in all the developmental stages examined, indicating that mRNAs for the steroidogenic enzymes required to convert cholesterol to androgens are present in the avian embryo before gonadal differentiation. In contrast, P-450arom mRNA was detected in female embryos during days 5-9 of incubation but not in male embryos throughout incubation. The onset of P-450arom gene expression at day 5 coincides with the stage of gonadal differentiation, corroborating the role of estrogen in the process of gonadal differentiation in chicken.
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PMID:Expression of five steroidogenic genes including aromatase gene at early developmental stages of chicken male and female embryos. 1065 98

In Experiment 1, the influence of exogenous GH on steroid secretion by granulosa and theca interna cells recovered from small (1-3 mm), medium (4-6 mm) and large (8-12 mm) follicles was tested. In the second experiment, theca cells (Tc) and granulosa cells (Gc) obtained from large follicles were cultured separately or in two types, Tc/Gc co-culture, where both types of cells were mixed in one well or Gc and Tc were separated by cell culture membrane inserts. In the third experiment, the influence of GH on the morphology of Gc and Tc cells and activity of Delta(5),3beta-hydroxysteroid dehydrogenase (3beta-HSD) was studied. Cells were grown in the control medium (M199+5% of calf serum) or supplemented with 100 ng/ml GH. Testosterone (10(-7) M) was added as the aromatase substrate to granulosa cells cultures. The media were assayed after 48 h of culture for progesterone and oestradiol by RIA. GH added to the culture media had no effect on oestradiol and progesterone secretion by granulosa cells isolated from small and medium follicles while it stimulated both oestradiol and progesterone secretion by Gc isolated from large preovulatory follicles. A stimulatory effect on oestradiol secretion by Tc isolated from all size follicles was observed. GH did not stimulate progesterone secretion by Tc isolated from small follicles but stimulated progesterone secretion by Tc isolated from medium and large preovulatory follicles. Both co-culture systems exhibited synergistic effect on oestradiol secretion. The stimulatory effect on progesterone secretion under the influence of GH was observed in Gc cultured alone and Tc cultured alone. In contrast, the secretion of progesterone was attenuated in both co-culture systems and the addition of GH further augmented this attenuation. A statistically significant increase in oestradiol secretion was observed in all culture conditions. The addition of GH to the culture medium stimulated the activity of 3beta-HSD compared with the control culture from both types of cells. In conclusion, the present studies indicate that there are direct and follicular development stage dependent actions of GH on steroidogenesis of porcine follicular cells.
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PMID:Response of porcine theca and granulosa cells to GH during short-term in vitro culture. 1070 Jun 49


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