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)

The 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase (3beta-HSD) isoenzymes catalyze an essential step in the formation of all classes of active steroid hormones. We have recently shown that 3beta-HSD type 1 gene expression is specifically induced by interleukin (IL)-4 and IL-13 in breast human cancer cell lines and in normal human mammary epithelial cells in primary culture. There is evidence that IL-4 stimulates bifurcating signaling pathways in which the signal transducer and activator of transcription-6 (Stat6)-signal pathway is involved in differentiation and gene regulation, whereas insulin receptor substrate (IRS) proteins mediate the mitogenic action of IL-4. In fact, we have shown that Stat6 was activated by IL-4 in all cell lines studied where IL-4 induced 3beta-HSD expression, but not in those that failed to respond to IL-4. The present study was designed to investigate the potential contribution of IRS proteins and their downstream targets to IL-4-induced 3beta-HSD type 1 gene expression. IL-4 rapidly induced IRS-1 and IRS-2 phosphorylation in ZR-75-1 human breast cancer cell lines. Moreover, insulin-like growth factor (IGF)-I and insulin, which are well known to cause IRS-1 and IRS-2 phosphorylation, increased the stimulatory effect of IL-4 on 3beta-HSD activity. IRS-1 and IRS-2 are adapter molecules that provide docking sites for different SH2-domain-containing proteins such as the phosphatidylinositol (PI) 3-kinase. In this light, the inhibition of IL-4-induced 3beta-HSD expression by wortmannin and LY294002, two potent PI 3-kinase inhibitors, indicates the probable involvement of the PI 3-kinase signaling molecules in this response to IL-4. Furthermore, it has been suggested that the IRS proteins are part of the signaling complexes that lead to activation of the mitogen-activated protein (MAP) kinase by insulin; thus we investigated the potential role of the MAP kinase (MAPK) cascade in the IL-4 action. In ZR-75-1 cells, both the activation of MAPK by IL-4 and the IL-4-induced 3beta-HSD activity were completely blocked by PD98059, an inhibitor of MAPK activation. Wortmannin also blocked MAPK activation by IL-4, IGF-I, and insulin, suggesting that the MAPK cascade acts as a downstream effector of PI 3-kinases. To further understand the cross-talk between signaling pathways involved in IL-4 action, we investigated the possible involvement of protein kinase C (PKC). The potential role of PKC was suggested by the observation that the well known PKC activator phorbol-12-myristate-13-acetate (PMA) potentiated the IL-4-induced 3beta-HSD activity. Taken together, these findings suggest the existence of a novel mechanism of gene regulation by IL-4. This mechanism would involved the phosphorylation of IRS-1 and IRS-2, which transduce the IL-4 signal through a PI 3-kinase- and MAPK-dependent signaling pathway. The inability of IGF-I, insulin, and PMA to stimulate 3beta-HSD expression by themselves in the absence of IL-4 makes obvious the absolute requirement of an IL-4-specific signaling molecule. Our findings thus suggest that the multiple pathways downstream of IRS-1 and IRS-2 must act in cooperation with the IL-4-specific transcription factor Stat6 to mediate the induction of 31beta-HSD type 1 gene expression in ZR-75-1 human breast cancer cells.
 ...
PMID:Multiple signaling pathways mediate interleukin-4-induced 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase type 1 gene expression in human breast cancer cells. 1067 96

Mutations in the 3beta-hydroxysteroid dehydrogenase (3beta-HSD) type II gene have been reported in a small number of affected females. We report a 46,XX girl born to consanguineous parents from Chile. At birth, she had normal but hyperpigmented female external genitalia. At 60 days she presented salt loss. At 20 months, the diagnosis of classic salt-losing 3beta-HSD deficiency was made based on an elevated serum 17-hydroxpregnenolone concentration and a high 17 hydroxypregnenolone/17-hydroxyprogesterone ratio. Genomic DNA was amplified by PCR and screened for mutations by denaturing gradient gel electrophoresis and directly sequenced. A novel homozygous E135* mutation was found in the 3beta-HSD type II gene of the patient while her parents were heterozygotes. This novel nonsense homozygous E135* mutation led to encode a predicted truncated 134 amino acid protein instead of the native 371 amino acid 3beta-HSD type II protein. This predicted product is consistent with the severe 3beta-HSD deficiency in this girl.
 ...
PMID:A novel homozygous nonsense mutations E135* in the type II 3beta-hydroxysteroid dehydrogenase gene in a girl with salt-losing congenital adrenal hyperplasia. Mutations in brief no. 168. Online. 1069 26

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.
 ...
PMID:Response of porcine theca and granulosa cells to GH during short-term in vitro culture. 1070 Jun 49

The isoflavones daidzein, genistein, biochanin A and formononetin inhibit potently and preferentially the gamma-isozymes of mammalian alcohol dehydrogenase (gammagamma-ADH), the only ADH isozyme that catalyzes the oxidation of 3beta-hydroxysteroids. Based on these results, we proposed that these isoflavones might also act on other enzymes involved in 3beta-hydroxysteroid metabolism. Recently, we showed that they indeed are potent inhibitors of a bacterial beta-hydroxysteroid dehydrogenase (beta-HSD). To extend this finding to the mammalian systems, we hereby purified, characterized and studied the effects of isoflavones and structurally related compounds on, a bovine adrenal 3beta-hydroxysteroid dehydrogenase (3beta-HSD). This enzyme catalyzes the oxidation of 3beta-hydroxysteroids but not 3alpha-, 11beta- or 17beta-hydroxysteroids. The same enzyme also catalyzes 5-ene-4-ene isomerization, converting 5-pregnen 3, 20-dione to progesterone. The K(m) values of its dehydrogenase activity determined for a list of 3beta-hydroxysteroid substrates are similar (1 to 2 microM) and that of its isomerase activity, determined with 5-pregnen 3, 20-dione as a substrate, is 10 microM. The k(cat) value determined for its isomerase activity (18.2 min(-1)) is also higher than that for its dehydrogenase activity (1.4-2.4 min(-1)). A survey of more than 30 isoflavones and structurally related compounds revealed that daidzein, genistein, biochanin A and formononetin inhibit both the dehydrogenase and isomerase activity of this enzyme. Inhibition is potent and concentration dependent. IC(50) values determined for these compounds range from 0.4 to 11 microM, within the plasma and urine concentration ranges of daidzein and genistein of individuals on vegetarian diet or semi-vegetarian diet. These results suggest that dietary isoflavones may exert their biological effects by inhibiting the action of 3beta-HSD, a key enzyme of neurosteroid and/or steroid hormone biosynthesis.
 ...
PMID:Bovine adrenal 3beta-hydroxysteroid dehydrogenase (E.C. 1.1.1. 145)/5-ene-4-ene isomerase (E.C. 5.3.3.1): characterization and its inhibition by isoflavones. 1070 8

Eubacterium sp. GLH with Ruminococcus sp. PO1-3 and Clostridium innocuum ES24-06 possessing enzymes involved in the metabolism of glycyrrhizin (GL) was cultured in GAM medium with and without 1.0 mM GL or 1.0 mM glycyrrhetic acid (GA). GL (1.0 mM) enhanced 3alpha-hydroxyglycyrrhetinate (3alpha-hydroxyGA) dehydrogenase activity, GA (1.0 mm) suppressed 3alpha-hydroxyGA dehydrogenase activity, GL beta-D-glucuronidase activity and the mixed bacterial growth, and GL and GA showed almost no change in a lower level of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) activity during 5 d of culture. GL (1.0 mM) and GA (1.0 mM) were metabolized to a small amount of GA and a negligible amount of 3-oxo-glycyrrhetic acid (3-oxo-GA) and 3alpha-hydroxyGA, and to a negligible amount of 3-oxo-GA, respectively, by these mixed bacteria. These amounts coincided with those of metabolites produced from 1.0 mM GL and 1.0 mM GA added to these mixed bacteria after 24 h culture. Whole bacteria and sonicated bacteria derived from the collection of these mixed bacteria reached a maximal stage and metabolized GL to a relatively large amount of GA and 3-oxo-GA, and a negligible amount of 3alpha-hydroxyGA and GA to a small amount of 3-oxo-GA and 3alpha-hydroxyGA within 180 min. GL beta-D-glucuronidase with 3beta-HSD and 3alpha-hydroxyGA dehydrogenase partially purified from each bacterium was converted GL to 3alpha-hydroxyGA, producing metabolites of about 60% after 10 min of incubation. These mixed bacteria possessed high enzyme activities could produce the metabolites of GL in under one hour under conditions.
 ...
PMID:Hasty effect on the metabolism of glycyrrhizin by Eubacterium sp. GLH with Ruminococcus sp. PO1-3 and Clostridium innocuum ES24-06 of human intestinal bacteria. 1070 2

Expression of cytochrome P450 cholesterol side chain cleavage (P450scc) and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) mRNAs was examined in chicken embryonic adrenal glands and gonads between days 4 and 12 of incubation. In situ hybridization analysis showed that 3beta-HSD mRNA appeared on day 5 of incubation in the adrenal glands and on day 6 in the gonads, while P450scc mRNA was expressed on day 7 in both the adrenal glands and the gonads. Cells expressing both enzyme mRNAs were distributed in the steroidogenic tissues of the adrenal glands and in the medullary cords of the gonads. From days 9 to 11 of incubation, P450scc mRNA expression was not found in the majority of both the adrenal glands and the gonads, but was detected again in both on day 12, although 3beta-HSD mRNA was constitutively expressed during this period. Changes in the expression pattern of P450scc mRNA are paralleled by changes in the plasma corticosterone level reported previously. Therefore, it is suggested that P450scc is essential to embryogenesis.
 ...
PMID:Expression of cytochrome P450 cholesterol side chain cleavage and 3beta-hydroxysteroid dehydrogenase during embryogenesis in chicken adrenal glands and gonads. 1075 71

Isoflavones and others phytoestrogens have been suggested to be anticarcinogenic. Anti-aromatase, antiestrogenic or antiproliferative actions of these compounds have been postulated and related to the observation that there is a reduced incidence of breast cancer associated with diet. In this study, we explored some mechanisms by which they can exert cancer-preventive effects. Phytoestrogens were tested for estimating anti-aromatase, anti-3beta-hydroxysteroid dehydrogenase delta5/delta4 isomerase (3beta-HSD) and anti-17beta-hydroxysteroid dehydrogenase (17beta-HSD) activities in human placental microsomes. We found that isoflavonoids and compounds which presented the phenolic B ring in the 3 position on the pyran ring preferentially inhibited 3beta-HSD and/or 17beta-HSD activities than aromatase activity. We also evaluated their interactions with the estrogen receptor using a stably transfected human breast cancer cell line (MVLN). On the other hand phytoestrogens were evaluated for their effects on the proliferation in estrogen-dependent (MCF-7) and independent (MDA-MB231) human breast cancer cells. We established a relationship structure-activity and determined regions or/and substituents essential for these different activities. However, at high concentrations it seems that some phytoestrogens exert their protection against breast cancer through other estrogen-independent mechanisms.
 ...
PMID:Effects of phytoestrogens on aromatase, 3beta and 17beta-hydroxysteroid dehydrogenase activities and human breast cancer cells. 1075 63

To find an explanation for the possible working mechanism of laparoscopic ovarian electrocautery for the treatment of anovulation in polycystic ovarian syndrome (PCOS), we evaluated the distribution of steroidogenic enzymes involved in the synthesis of ovarian androgens in surgical pathology specimens of entire polycystic ovaries. A total of 13 formalin-fixed and paraffin-embedded samples of the ovaries of patients with clinically proven PCOS were immunostained with specific antibodies against cholesterol side-chain-cleavage enzyme (P450scc), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 17alpha-hydroxylase (P450c17) and adrenal 4-binding protein (Ad4BP), a transcription factor of steroidogenic enzymes. Follicular theca cells of all ovaries demonstrated marked immunoreactivity for Ad4BP, P450scc, 3beta-HSD and P450c17. Granulosa cells of seven ovaries expressed Ad4BP, while granulosa cells of three ovaries also showed P450scc. In the granulosa cells of all ovaries, 3beta-HSD and P450c17 immunoreactivity was not observed. In the stroma, luteinized cells of most ovaries demonstrated Ad4BP, P450scc, 3beta-HSD and P450c17 immunoreactivity, but at a much lower level compared with the follicular theca cells. Non-luteinized stromal cells sporadically demonstrated Ad4BP, P450scc, 3beta-HSD and P450c17 immunoreactivity. The stromal steroidogenic cells were mainly located in the ovarian cortex, except for some hilus steroidogenic cells. These data demonstrate that in polycystic ovaries, androgens are mainly produced in the follicular theca cells and to some extent in luteinized stromal cells. This suggests that the working mechanism of laparoscopic electrocautery of the ovary is primarily explained through the reduction of ovarian hyperandrogenism by coagulation of follicular theca cells and concomitant stroma.
 ...
PMID:Distribution of steroidogenic enzymes involved in androgen synthesis in polycystic ovaries: an immunohistochemical study. 1077 48

The 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) play a key role in the synthesis of sex steroids. The hallmark of this family of enzymes is the interconversion, through their oxydoreductive reactivity at position C17, of 17-keto- and 17beta-hydroxy-steroids. Because this reaction essentially transforms steroids having low binding activity for the steroid receptor to their more potent 17beta-hydroxysteroids isoforms, it is crucial to the control of the physiological activities of both estrogens and androgens. The human placenta produces large amounts of progesterone and estrogens throughout pregnancy. The placental type 1 17beta-HSD enzyme (E17beta-HSD) catalyzes the reduction of the low activity estrogen, estrone, into the potent estrogen, estradiol. We studied the cell-specific expression of type 1 17beta-HSD in human term placental villous tissue by combining in situ hybridization to localize type 1 17beta-HSD mRNA with immunohistochemistry using an antibody against human placental lactogen, a trophoblast marker. Immunolocalization of E17beta-HSD was also performed. To ascertain whether other steroidogenic enzymes are present in the same cell type, cytochrome P450 cholesterol side-chain cleavage (P450scc), P450 aromatase, and type 1 3beta-hydroxysteroid dehydrogenase (3beta-HSD) were also localized by immunostaining. Our results showed that the syncytium is the major steroidogenic unit of the fetal term villi. In fact, type 1 17beta-HSD mRNA and protein, as well as P450scc, P450 aromatase, and 3beta-HSD immunoreactivities were found in these cells. In addition, our results revealed undoubtedly that extravillous cytotrophoblasts (CTBs), e.g. those from which cell columns of anchoring villous originate, also express the type 1 17beta-HSD gene. However, CTBs lying beneath the syncytial layer, e.g. those from which syncytiotrophoblasts develop, contained barely detectable amounts of type 1 17beta-HSD mRNA as determined by in situ hybridization. These findings, along with those from other laboratories confirm the primordial role of the syncytium in the synthesis of steroids during pregnancy. In addition, our results indicate for the first time that CTBs differentiating along the invasive pathway contain type 1 17beta-HSD mRNA.
 ...
PMID:Localization of type 1 17beta-hydroxysteroid dehydrogenase mRNA and protein in syncytiotrophoblasts and invasive cytotrophoblasts in the human term villi. 1081 Feb 85

The enzyme complex 3beta-hydroxysteroid dehydrogenase isomerase/delta5-delta4 (3beta-HSD) is involved in the biosynthesis of all classes of active steroids. In this study, the presence of 3beta-HSD was defined in rat tracheal cartilage. The expression of the 3beta-HSD gene was examined by Northern blot analysis from 30-day-old rats. Western blot and immunohistochemical localization were also performed with antibodies raised against purified human placental 3beta-HSD to obtain further information on the expression of 3beta-HSD protein during fetal and postnatal periods of development in rat cartilage. Northern blot analysis using an oligonucleotide common to the 4 known 3beta-HSD isoforms showed 3beta-HSD mRNA corresponding to a transcript of 1.7 kb. Furthermore, a 42 KDa protein band was detected in the tracheal cartilage extracts by Western blot analysis. Immunostaining for 3beta-SD was observed in chondrocytes. The first expression was detected on the 17th day of fetal life by Western blot and immunohistochemistry. Immunoreactivity of 3beta-HSD showed a significant increase at 7 and 15 days after birth, and then remained unchanged through adulthood, in agreement with the data of the Western blot. Our results demonstrated the expression for 3beta-HSD in the tracheal cartilage at both the mRNA and protein levels during fetal life and postnatal development of the rat. These results suggest that 3beta-HSD may synthesize certain steroids which play major roles in differentiation and maintenance of function during development of rat cartilage.
 ...
PMID:Expression of 3 beta-hydroxysteroid/dehydrogenase/delta5-delta4/isomerase in the tracheal cartilage of the rat. 1083 29


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