Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adrenarche is the increase of adrenal androgen secretion, mainly dehydroepiandrosterone and dehydroepiandrosterone sulfate, that occurs during prepuberty in higher primates. This event takes place at about 6-8 y of age in humans. It had been postulated that adrenarche might reflect an increase in the 17,20 lyase:17OH-ase activity ratio of microsomal cytochrome P450c17. However, studies to demonstrate this mechanism have been unsuccessful. Because it has been described that virilizing adrenocortical carcinomas have high dehydroepiandrosterone sulfate secretion and low 3beta-hydroxysteroid dehydrogenase (3betaHSD) activity, in this study we evaluated the possible existence of maturative changes of the level of 3betaHSD type II mRNA in 11 normal prepubertal and early pubertal human adrenals. Adrenal glands from subjects aged 0.1 to 13 y were obtained from organ donors, patients undergoing resection of the kidney for renal neoplasms or necropsies with less than 6 h of postmortem time. The expression of 3betaHSD type II gene was studied by dot blot in all samples and by relative reverse transcriptase (RT)-PCR in nine samples. The size of the transcripts was evaluated by Northern blot. Hybridization was performed using labeled human 3betaHSD cDNA probes. The uniformity of loading was tested using labeled human beta actine cDNA. The relative intensities of hybridization signals were quantified by scanning densitometry. The expected bands after relative RT-PCR were eluted, and radioactivity was measured in a scintillation counter. For the analysis of the results, subjects were divided into two groups as a function of age: group 1, less than 8 y (n = 6; range 0.1-2.48 y) and group 2, equal or older than 8 y (n = 5; range 8-13 y). 3BetaHSD type II mRNA expression, analyzed by dot blot and relative RT-PCR, was significantly higher (p < 0.05) in group 1 (median and range 4.99, 0.50-8.00 and 16.3, 13.5-40.0 arbitrary units, respectively) than in group 2 (0.15, 0.12-0.75 and 5.66, 3.18-13.0, respectively). In conclusion, we have shown a decrease of the expression 3betaHSD type II gene as a function of age in prepubertal and early pubertal normal human adrenal tissue. This maturative change might be involved in the mechanism of human adrenarche.
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PMID:Decrease in the expression of the 3beta-hydroxysteroid dehydrogenase gene in human adrenal tissue during prepuberty and early puberty: implications for the mechanism of adrenarche. 1008 59

An elevation in plasma estrogen levels is believed to play a key role in the pathogenesis of breast cancer. The conversion of estradiol-17beta (E2) to estrone (E1) by 17beta-hydroxy steroid dehydrogenase type 4 (17-HSD4) represents a major pathway of its inactivation in cells. In this study the potential relationship between lipoprotein peroxidation products and E2 metabolism was examined. It was noted that oxidized low-density lipoprotein (OX-LDL), not native LDL, caused a time- and concentration-dependent inhibition of the conversion of labeled E2 to E1 in THP-1 macrophage cells. Further studies noted that among the lipoprotein peroxidation products examined, malondialdehyde (MDA) caused a marked decrease in this reaction, whereas hexanal and a variety of oxysterols had no effect. This inhibition of E1 formation from E2 in THP-1 cells was confirmed by the quantitation of estrone formed with high-pressure liquid chromatography and by the expression of 17-HSD4 by reverse transcriptase-polymerase chain reaction. MDA added to Hep G2 cells showed a similar trend in E1 formation. These results suggest that increased oxidative stress and lipid peroxidation might result in decreased inactivation of biologically active estrogen. This might be important in postmenopausal women undergoing estrogen replacement therapy.
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PMID:Evidence for interference in estradiol-17beta inactivation to estrone by oxidized low-density lipoprotein and selected lipid peroxidation products. 1048 10

The signal initiating ovarian theca cell (TC) differentiation is gonadotropin independent because theca precursor cells do not contain LH receptors. Previously we demonstrated that preantral follicles produce paracrine TC differentiating factors that promote androgen production by an LH-independent mechanism. This study tested the effects of two granulosa cell-produced peptides, insulin-like growth factor-I (IGF-I) and stem cell factor (SCF), on TC differentiation and androgen production. Neutralizing antibodies to either IGF-I or SCF blocked the stimulatory effects of follicle-conditioned medium on TC precursor differentiation more than 90%. The TC isolated from the ovaries of hypophysectomized immature rats by percoll gradient centrifugation were cultured (48 h) with and without SCF (0-100 ng/ml) and IGF-I (0-100 ng/ml) to test their effects on TC differentiation. Androsterone in the medium was measured by RIA. Luteinizing hormone receptor, steroidogenesis acute regulatory protein (StAR), CYP11A, CYP17, and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) mRNAs were measured by specific reverse transcriptase polymerase chain reaction assays. Stem cell factor or IGF-I alone did not stimulate androsterone production but in combination caused a concentration-dependent increase in androsterone levels. Maximum androsterone levels were less than those stimulated by LH (0.1 ng/ml) alone. Although IGF-I synergistically augmented LH stimulation of androsterone production, SCF did not alter LH-stimulated androsterone production in the presence or absence of IGF-I. Stem cell factor alone had no effect on LH receptor, StAR, CYP11A, and 3beta-HSD mRNA expression but decreased CYP17 mRNA levels. Insulin-like growth factor-I alone had no effect on StAR or CYP17 mRNA expression but increased LH receptor, CYP11A, and 3beta-HSD mRNA levels. In combination, SCF plus IGF-I increased the expression of all five mRNAs. These data support the conclusion that IGF-I and SCF are important regulators of TC differentiation.
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PMID:Stem cell factor and insulin-like growth factor-I stimulate luteinizing hormone-independent differentiation of rat ovarian theca cells. 1115 46

The changes in endometrial homeostasis found in women with polycystic ovarian syndrome (PCOS) could be associated with alterations in the intracrine metabolism of steroid hormones. The uptake of dehydroepiandrosterone-sulphate (DHEA-S), precursor of the intracrine pathway, is achieved by transporters, such as organic anion transporter polypeptides (OATPs), and molecules with oestrogenic activity, such as androst-5-ene-3beta,17beta-diol (androstenediol), can be generated. We aimed to determine androstenediol generation and the expression of OATPs in human endometria throughout the menstrual cycle and in endometria from PCOS women. Endometrial samples were obtained from control women in the proliferative phase (control endometria (CEp), n=7), secretory phase (CEs, n=7), and from PCOS patients (PCOSEp, n=7). The mRNA levels of OATP-B, OATP-D and OATP-E were measured by reverse transcriptase polymerase chain reaction (RT-PCR) and protein levels of OATP-E by immunofluorescence; 3beta-hydroxysteroid dehydrogenase (HSD) by immunohistochemistry/Western blot; the metabolism of DHEA to androstenediol was evaluated by thin layer chromatography-high-performance liquid chromatography (TLC-HPLC). Lower levels of OATP-E transcript were obtained in PCOSEp (p<0.05) compared with CEp, while OATP-E protein levels (p<0.05) and DHEA conversion to androstenediol (p<0.01) were higher in PCOSEp. Lower 3beta-(hydroxysteroid dehydrogenase) HSD protein levels were found in PCOSEp (p<0.05) (Western blot, immunohistochemistry). These results reveal a higher capacity of the endometria from PCOS women to metabolise DHEA to androstenediol, which, coupled with the high oestrogen sensitivity previously found in these endometria, may account for the increase in cell proliferation in PCOSEp already reported.
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PMID:The conversion of dehydroepiandrosterone into androst-5-ene-3beta,17beta-diol (androstenediol) is increased in endometria from untreated women with polycystic ovarian syndrome. 2062 Jan 58