Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q7LGC8 (HSD)
 3,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For preventing the reduction of bone mass in postmenopausal women, oestrogen replacement is known to be useful and the importance of sex steroids in bone metabolism in both sexes is well established. The presence of steroid-converting-enzyme activities in various osteoblast and osteoblast-like cells has been demonstrated using in vitro culture systems. In the present study, we assessed the expression of messenger ribonucleic acid (mRNA) for aromatase, steroid sulphatase, 5 alpha-reductase, 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) and 3 beta-HSD by reverse transcription-polymerase chain reaction in the human osteoblast-like cell lines, MG 63 and HOS. Oestrogen, androgen and progesterone receptor mRNAs were also measured. Expression of mRNA for these enzymes and receptors was found in both cell lines without induction. From these and previous findings, we conclude that osteoblast-like cells have the capacity to form biologically potent oestrogens and androgens from peripheral circulating steroids. This may indicate an important role of bone in facilitating hormonal action.
 ...
PMID:Steroid formation in osteoblast-like cells. 951 72

The hormonal basis for masculine song development in the zebra finch remains unidentified. To understand how steroids are differentially supplied to the brains of males and females to cause sexually dimorphic development of this behavior, we have studied the steroidogenic capability of zebra finch tissues during early development (1 to 8 days posthatching). Here, we report on the use of cultures of whole gonads, adrenals, and telencephalons to measure the activities of two steroidogenic enzymes: aromatase, the enzyme that catalyzes the conversion of androgen to estrogen, and 3beta-hydroxysteroid dehydrogenase/delta4-delta5 isomerase (3beta-HSD), the enzyme that converts pregnenolone into progesterone. We also examined the effect of cAMP on aromatase activity in these tissues as this intracellular second messenger has been shown previously to regulate aromatase in both central and peripheral tissues of other species. In untreated cultures, aromatase was detected at the highest levels in male and female telencephalon and in ovary. Dibutyryl (dB)-cAMP had no significant effect on aromatase activity in any tissue. However, after dB-cAMP treatment, estrogens were regularly detected in cultures of whole testes. Although this activity was relatively low when compared to total activity found in other tissues, due to the small size of the testes at this age of development, the specific activity (per milligram of protein) might be high enough to produce some estrogen. Adrenal aromatase was unconfirmed in the presence or absence of cAMP. 3Beta-HSD activity was undetected in brain but was detected in gonads and adrenals from all birds. There were no significant differences in gonadal or adrenal 3beta-HSD activity between males and females. Although these data present the first evidence for testicular aromatase in the zebra finch, they provide no evidence to support a mechanism to generate a greater estrogenic signal in male zebra finches after hatching.
 ...
PMID:Activities of aromatase and 3beta-hydroxysteroid dehydrogenase/delta4-delta5 isomerase in whole organ cultures of tissues from developing zebra finches. 957 Oct 11

In the analysis of the regulation of human corpus luteum, it is very important to localize the sites of specific steroid hormone production to obtain a better understanding of luteal function. We have examined expression of steroidogenic enzymes, steroid receptors, and adrenal 4 binding protein (Ad4BP), a transcription factor of steroidogenesis, in corpus luteum of normal cycling human ovary. Corpus luteum can be classified into four different stages from ovulation to complete regression or fibrosis based on these findings: (1) corpus luteum, (2) steroid-producing degenerating corpus luteum or SPDCL, (3) nonsteroid producing or NSPDCL, and (4) corpus albicans. Corpus luteum in the luteal phase is characterized as follows: (a) the expression of P450scc (cholesterol side chain cleavage), 3 beta HSD (hydroxysteroid dehydrogenase), and Ad4BP in almost all the luteinized granulosa and theca cells, consistent with active progesterone biosynthesis; (b) expression of estrogen-producing P450arom (aromatase) in luteinized granulosa cells, indicating active estrogen production and that of P450c17 (17 alpha hydroxylase) in luteinized theca cells, and (c) expression of progesterone receptor (PR) and androgen receptor (AR) in both luteinized granulosa and theca cells. SPDCL correspond to corpus luteum undergoing regression or degeneration in the following cycle and are characterized as follows: (a) absence of all the steroidogenic enzymes and Ad4BP in the luteinized granulosa cells, suggestive of hormonally inactive nature of these cells and (b) marked expression of P450scc, 3 beta HSD, P450c17 and Ad4BP in luteinized theca cells. NSPDCL is characterized as the absence of all the steroidogenic enzymes and sporadic expression of Ad4BP in luteinized theca cells. These findings indicate that luteal cells remain even after losing expression of steroidogenic enzymes, consistent with a prolonged process of degeneration or regression of human corpus luteum. In corpus albicans, all the cells were replaced by fibrosis and steroidogenic enzymes; steroid receptors and Ad4BP were not expressed at all. Localization of steroidogenesis in human corpus luteum has thus provided new insights into understanding of its biological features.
 ...
PMID:Localization of steroidogenesis and steroid receptors in human corpus luteum. Classification of human corpus luteum (CL) into estrogen-producing degenerating CL, and nonsteroid-producing degenerating CL. 958 Sep 43

AME has been a crucial experiment of biology from which much has been learnt about corticosteroid hormone action and mineralocorticoid hypertension. 11 beta-HSD is an important pre-receptor pathway determining corticosteroid hormone action. Any tissue expressing 11 beta-HSD1 or 11 beta-HSD2 can clearly modulate glucocorticoid and mineralocorticoid action independent of circulating concentrations. A series of related enzymes operates in a similar fashion to determine hormone action for other members of the thyroid/steroid hormone receptor superfamily (e.g. 17 beta-HSD, 25-hydroxyvitamin D 1 alpha-hydroxylase, aromatase, 5'-deiodinase, 5 alpha-reductase). Endocrinologists have been obsessed with measuring the concentrations of a hormone in the circulation and making their decisions on the basis of these results, whether or not that hormone is involved in the pathogenesis of a disease process. Such an approach needs to be revised, with greater emphasis on considering the action of a hormone within a given tissue and, in turn, on the role of these enzymes in the pathogenesis of human disease.
 ...
PMID:Cortisol, hypertension and obesity: the role of 11 beta-hydroxysteroid dehydrogenase. 959 34

Postmenopausal loss of 17 beta-estradiol (E2) in women is associated with decreased bone mineral density and increased susceptibility to osteoporotic bone fracture. These changes in bone status are assumed to be due to circulating levels of the hormone; therapeutic replacement of E2 can alleviate the bone disease. However, recent reports have shown that human osteoblastic (OB) cells are able to synthesize estrogens locally, via expression of the enzyme aromatase. In this study, we have characterized the expression and activity of aromatase and 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) in rat OB cell lines. Aromatase activity in ROS 17/2.8, ROS 25/1, and UMR 106 cells was similar to that shown in human OB cells, with the highest levels of activity observed in the more differentiated ROS 17/2.8 cells (Vmax = 45 pmol/h/mg of protein). The rat OB cells also showed 17 beta-HSD activity, with the predominant metabolism in all three cell lines being estrone (E1) to E2. As with aromatase, the highest activity was observed in ROS 17/2.8 cells (Vmax = 800 pmol/h/mg of protein). Northern analyses indicated the variable presence of transcripts corresponding to the type 1, 2, 3, and 4 isoforms of 17 beta-HSD. Further analysis of androstenedione metabolism indicated that the net effect of aromatase and 17 beta-HSD activity varied with cell type and culture treatment. All three OB cell lines were able to synthesize E1, E2, and testosterone from androstenedione, although activity varied between OB cell types. Regulatory effects were observed with 1,25-dihydroxyvitamin D3 (positive) and dexamethasone (negative). These data suggest that local synthesis of sex hormones is an important function of OB cells and may play a key role in the modulation of bone turnover independent of circulating hormone concentrations.
 ...
PMID:Characterization of aromatase and 17 beta-hydroxysteroid dehydrogenase expression in rat osteoblastic cells. 962 31

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.
 ...
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.
 ...
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.
 ...
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.
 ...
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.
 ...
PMID:Studies on the origin of ovarian interstitial tissue and the incidence of endometrial hyperplasia in domestic and feral cats. 1052 57


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>