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)

Two types of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) have been identified in different tissues. Type 1 has both oxidase and reductase activities interconverting cortisol and cortisone, whereas type 2 has only oxidase activity converting cortisol to cortisone. It has been proposed that placental 11 beta-HSD controls the passage of maternal glucocorticoids to the fetal circulation. However, little is known about the regulation of 11 beta-HSD in the human placenta and fetal membranes. We cultured human term placental trophoblast and chorionic trophoblast cells to examine effects of nitric oxide donors, sodium nitroprusside (SNP) and S-nitroso-N-acetyl penicillamine (SNAP), on the activity and messenger RNA (mRNA) expression of 11 beta-HSD. At 72 h of culture, placental trophoblast formed syncytial clumps that were cytokeratin positive and displayed mainly type 2 oxidase activity, although some type 1 reductase activity was detectable. Chorion preparations contain greater than 90% trophoblast cells as demonstrated by immunostaining for cytokeratin and less than 5% vimentin positive cells. Type 1 reductase activity predominated in the chorionic trophoblast cells with barely detectable type 1 or type 2 oxidase activity. Both SNP (1-400 microM) and SNAP (1 mM) inhibited placental 11 beta-HSD type 2 oxidase activity but not type 1 reductase activity either in placental or chorionic cells. An inhibitory effect on type 2 oxidase activity was reproduced in part by 8-bromo cGMP, blocked partially by the guanylate cyclase inhibitor LY83583 (1 microM), but not by an ADP-ribosylation inhibitor N, N'-hexamethylene-bis-acetamide (HMBG) (10 mM). SNP also suppressed the expression of type 2 mRNA in cultured placental trophoblast in a dose-dependent manner, and this effect was also blocked by LY83583. We conclude that human placental trophoblast possesses predominantly 11 beta-HSD type 2 oxidase activity, whereas chorionic cells possess mainly type 1 reductase activity under the culture conditions employed. Nitric oxide specifically attenuated 11 beta-HSD type 2 oxidase activity as well as its mRNA expression in the placental trophoblast. The effect was mediated at least partially through the cGMP pathway, although an alternative pathway other than ADP-ribosylation may exist.
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PMID:Differential regulation of 11 beta-hydroxysteroid dehydrogenase type 1 and 2 by nitric oxide in cultured human placental trophoblast and chorionic cell preparation. 934 22

Studies were performed on cultured epithelial cells of the caput and cauda of epididymis stemming from male rats of inbred Wistar strain. The cultures were conducted on a full medium enriched with 5% fetal calf serum in the presence or without exogenic androgens-T and DHT. The cells were identified by means of immunohistochemical reactions with the use of monoclonal antibodies against cytokeratin and desmin (Fig. 1, 2). All cells in the culture showed positive reaction to cytokeratin. At the same time there was a lack of desmin-positive cells. Through secreting the proteins, glycoproteins, glycolipids, phospholipids and number of other substances the epithelial cells of epididymis create an environment for maturating and storing of spermatozoa in lumen of the duct. Synthesis of these substances is possible thanks to the expression of genes defined for a given zone of epididymis, the expression being mainly regulated by androgen, although a share of estrogens is also evidenced in this process. The cytoplasm of epithelial cells of epididymis fails to reveal the presence of secretory granules, while the mechanism of releasing the secretion still continues to be controversial. There are also some and unverified suggestions about the capability of these cells to synthesize androgens. In connection with what was mentioned above, the objective of the work was to establish the mode of releasing the secretions by cultured epithelial cells of epididymis as well as to determine whether these cells synthesize androgens and if they may be the source of estrogens. Electron-microscopic observations disclosed a rich content of rough endoplasmic reticulum and structures similar to secretory units produced from concentrically arranged membranes encircling cytoplasm fragments in their interior (Fig. 10B, 14, 15A). There were protrusions of cytoplasm on the surface of cells. Released secretion was present between the cells. The apocrine way of releasing was confirmed also by scanning electron microscope. Numerous granular protrusions were released into the intercellular space (Fig. 19). The process of synthesis and release of secretion was androgen-dependent. Cells cultured without addition of exogenic androgens were characterized by disorganization of organelles and reduction of their number, particularly rough endoplasmic reticulum. The surface of cells was prevalently smooth, deprived from protrusions (Fig. 21). Very close neighbourhood, and sometimes a direct contact of lipid droplets and mitochondria with lamellar cristae as well as the presence of smooth endoplasmic reticulum observed in cytoplasm of cultured epithelial cells of epididymis, suggest their similarity to steroidogenic cells (Fig. 11A, 12). This is also indicated by the finding that these cells reveal the presence of active enzymes of the steroidogenesis pathway, 3 beta-HSD and 17 beta-HSD exhibited in histochemical reactions (Fig. 8, 9). RIA determination of hormones in the medium, wherein the epithelial cells had been cultured showed that the said cells synthesized and released DHEA, A and T, but in low and sometimes trace concentrations (Tab. 1-3). Lack of progesterone in medium of the cells on the 3rd and 5th days of culture indicates that the synthesis of testosterone and earlier forms of androgens proceeds using delta 5 metabolites, as it takes place in human testis. The cells' medium on the 3rd and 5th days of culture was found to disclose high concentration of 17 beta-estradiol (E2) (Tab. 4). E2 concentrations were always higher when the cells were grown without the addition of exogenic androgens. In this cases the cytoplasm of the cells displayed depolymerization of microtubules, which enhances the approximation to each other of structures participating in steroidogenesis and translocation of substrates and products of the consecutive stages of steroidogenesis. (ABSTRACT TRUNCATED)
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PMID:[Steroidogenesis in epithelial cells of rat epididymis]. 1046 48

Placental trophoblasts are an important source of endocrine, paracrine and autocrine acting hormones. The aim of the present study was to establish and evaluate a tissue culture model for bovine trophoblasts to study regulation of key genes of steroid hormone synthesis. Trophoblast cells were isolated from cotyledons by collagenase disaggregation and subsequent percoll density gradient centrifugation. The cells were seeded on collagen coated dishes and incubated for up to seven days. The cells were characterized for the presence of mesenchymal vimentin and epithelial cytokeratin filaments and for Dolichos biflorus agglutinin (DBA) binding, a marker for differentiated trophoblast giant cells. Transcripts of Hsd3b, Cyp17 and Cyp19 encoding 3beta-HSD, P450c17 and P450arom, the key enzymes of progesterone, androgen, and oestrogen biosynthesis, respectively, and of Csh1 encoding the trophoblast-specific hormone placental lactogen (PL) were measured by qPCR. Uninucleate cotyledonary epithelial cells and bi- and trinucleate trophoblast giant cells efficiently formed a dense cell layer on the collagen coated dishes within 24 h. Bi- and trinucleate cells showed DBA binding and weak or undetectable cytokeratin immunoreactivity. Vimentin-positive, fibroblast-like cells were found on top of this cell layer. Cyp19 transcripts were found in freshly dissociated but not in cultured cells. Cyp17 expression continuously increased, Hsd3b transcripts largely and rapidly increased during the first days in culture, followed by a decline after three days, whereas Csh1 decreased towards day seven. Serum free culture conditions significantly enhanced Cyp17 and Csh1 but not Hsd3b expression. The data indicate that collagen is a favourable substrate for cultured binucleate trophoblast giant cells. The cells represent an in vitro model to study the regulation of key genes of placental progesterone and androgen but not of oestrogen biosynthesis.
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PMID:Cultured bovine trophoblast cells differentially express genes encoding key steroid synthesis enzymes. 1845 33