Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The first step in the synthesis of all steroids is the cleavage of cholesterol side chain, catalyzed by an electron transport system located in mitochondria consisting of ferredoxin reductase, ferredoxin, and cytochrome P450scc. These proteins are present in adrenal, gonad, placenta, and some parts of the brain. In addition, ferredoxin and ferredoxin reductase are also found in the kidney and liver. Whereas ferredoxin reductase levels remain constant in the cell, ferredoxin and P450scc levels are stimulated by trophic hormones using cAMP as an intracellular messenger. The ferredoxin promoter is relatively simple, consisting of a TATA box and two Sp1-binding sites. This simple module is enough to direct cAMP-dependent transcription in a steroidogenic cell-specific fashion. The regulatory region for the P450scc gene is more complex, containing many protein binding sites for different regulation purposes. Its TATA box directs cAMP-dependent transcription in a cell-type-specific manner. A transcription factor, steroidogenic factor 1 (SF1), activates P450scc gene expression. The tissue-specific expression of the P450scc gene is probably accomplished through the interaction of SF1 with other protein factors located further upstream of the control region. SF1 may also be involved in the cAMP response. An upstream region binding to cAMP-Responsive Element Binding Protein CREB and AP1 can respond to cAMP for gene activation. These analyses of regulatory elements provide the structural architecture for transcriptional regulation of the ferredoxin and the CYP11A11 gene.
Steroids 1997 Jan
PMID:Transcriptional regulation of the CYP11A1 and ferredoxin genes. 902 12

We previously reported that tributyltin chloride (TBT) and triphenyltin chloride (TPT) powerfully suppressed human chorionic gonadotropin- and 8-bromo-cAMP-stimulated testosterone production in pig Leydig cells at concentrations that were not cytotoxic [Nakajima Y, Sato Q, Ohno S, Nakajin S. Organotin compounds suppress testosterone production in Leydig cells from neonatal pig testes. J Health Sci 2003;49:514-9]. This study investigated the effects of these organotin compounds on the activity of enzymes involved in testosterone biosynthesis in pig testis. At relatively low concentrations of TPT, 17beta-hydroxysteroid dehydrogenase (17beta-HSD; IC(50)=2.6microM) and cytochrome P450 17alpha-hydroxylase/C(17-20) lyase (IC(50)=117microM) activities were inhibited, whereas cholesterol side-chain cleavage cytochrome P450 and 3beta-HSD/Delta(4)-Delta(5) isomerase activities were less sensitive. Overall, TPT was more effective than TBT. TPT also inhibited both ferredoxin reductase and P450 reductase activities at concentrations over 30microM; however, TBT had no effect, even at 100microM. The IC(50) values of TPT were estimated to be 25.7 and 22.8microM for ferredoxin reductase and P450 reductase, respectively. The inhibitory effect of TPT (30microM) on microsomal 17beta-HSD activity from pig testis was eliminated by pretreatment with the reducing agents dithiothreitol (1mM) and dithioerythritol (1mM). On the other hand, TPT (0.03microM) or TBT (0.1microM) exposure suppressed the testosterone production from androstenedione in pig Leydig cells indicating that these organotins inhibit 17beta-HSD activity in vivo as well as in vitro, and the IC(50) values of TPT and TBT for 17beta-HSD activity were estimated to be 48 and 114nM, respectively. Based on these results, it appears possible that the effects of TBT and TPT are largely due to direct inhibition of 17beta-HSD activity in vivo.
Steroids 2005 Aug
PMID:Triphenyltin and Tributyltin inhibit pig testicular 17beta-hydroxysteroid dehydrogenase activity and suppress testicular testosterone biosynthesis. 1589 6

The C-7 cholesterol dehydrogenase (NVD), which converts cholesterol to 7-dehydrocholesterol (7-DHC) by 7,8-dehydrogenation, plays a pivotal role in the metabolism of cholesterol and steroid intermediates. The NVD protein was successfully expressed in insect Sf9 cells. To reduce the production cost for industrial application, the NVD gene was cloned into E. coli BL21(DE3). However, the His-tagged NVD protein showed poor binding to Ni-NTA resin, mainly due to the formation of inclusion bodies. Consequently, the expression and solubility of NVD were optimized by respectively fusing it with maltose-binding protein (MBP), glutathione S-transferase (GST), and the nonspecific DNA binding protein from Sulfolobus solfataricus (Sso7d) as solubility tags. The NVD fusion with MBP at the N-terminus and His-tag at the C-terminus achieved a high yield of the soluble enzyme. It was further purified by ion-exchange chromatography with 95.4% purity and with a 10.4% yield. The product 7-DHC, which is produced in a reaction catalyzed by NVD and ferredoxin reductase KshB, was initially identified by GC-MS. An analysis of the amino acid sequence alignment revealed a distinct Rieske-type iron-sulfur cluster and non-heme Fe2+-binding domain, which are evolutionarily conserved among NVD family enzymes.
Steroids 2019 12
PMID:Soluble expression, purification and biochemical characterization of a C-7 cholesterol dehydrogenase from Drosophila melanogaster. 3152 8