Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

In all species of crocodilians, sex is determined not by genetic mechanisms, but by the temperature at which the egg is incubated. In the American alligator (Alligator mississippiensis) the thermosensitive period (TSP) for sex determination is a 7- to 10-day window within stages 21-24 of development, around the middle third of the incubation period. Treating embryos with estrogen during the TSP produces female offspring, even at male incubation temperatures. Conversely, blocking embryonic estrogen synthesis at female-inducing temperature prevents development of the female phenotype. Therefore, it has been suggested that estrogen plays a role in determination of sex in the alligator. Estrogen is produced from an androgen substrate by cytochrome P450 aromatase (CYP19). If estrogen plays a critical role in sex determination, there should be differences in aromatase expression between embryos at male- and female-producing temperatures during the TSP. Therefore, to address this question, we cloned and characterized the alligator CYP19 cDNA. Based on the sequence information, a quantitative kinetic reverse transcriptase-polymerase chain reaction (TaqMan) assay was designed to measure expression of the alligator aromatase gene in RNA extracted from the gonadal and brain regions of alligator embryos incubated at male- or female-producing temperatures from prior to the TSP through hatching. Aromatase expression was detected in the brain region from the earliest stage tested (stage 20) through hatching. The hypothalamus had significantly higher expression than the forebrain or hindbrain in both male and female embryos. Expression was not significantly different in the gonadal region between embryos at male and female temperatures until after the TSP, when there was a dramatic increase in expression at female temperature. These data indicate that aromatase expression and, thus, estrogen production, are not the initial trigger for sex determination but play an essential role in ovarian differentiation in the alligator. J. Exp. Zool. 290:439-448, 2001.
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PMID:Alligator aromatase cDNA sequence and its expression in embryos at male and female incubation temperatures. 1155 51

Aromatase catalyzes the synthesis of estrogen from its androgen precursors. Estrogen is known to be important in regulating long bone growth and epiphyseal plate closure. To assess whether there may be growth plate-specific production of estrogen, we performed reverse transcriptase polymerase chain reaction (RT-PCR) to determine whether aromatase transcripts are present in the human growth plate. Immunohistochemistry was also employed to identify the specific sites of expression. Growth plates were obtained from an adolescent male and female undergoing ephysectomy to counter premature growth plate closure in the opposite leg. Aromatase transcripts were detected in RNA preparations from both growth plates. The aromatase protein was mainly expressed in the zone of maturation and the hypertrophic zone, with greatest expression in the latter. Since estrogen receptors are known to be expressed in chondrocytes, this data is consistent with a role for local estrogen production in the autocrine/paracrine control of long bone growth and growth plate maturation.
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PMID:Expression of aromatase in the human growth plate. 1156 7

It is well documented that estrogens have atheroprotective effects in humans. Peripheral aromatization of circulating androgens has been demonstrated to exert estrogenic actions in many human tissues, especially in men and post-menopausal women. Recently, production of estrogens mediated by aromatase was detected in cultured smooth muscle cells and aortic endothelial cells and it has been proposed that this in situ produced estrogen may influence the development of atherosclerosis. In this study, we first examined aromatase expression by immunohistochemistry in human aortic tissues obtained from 85 autopsy cases (50 males, 35 females, 49.6 +/- 2.9-year-old) and by mRNA in situ hybridization in 10 cases. We then semi-quantified the level of aromatase mRNA in aortic tissues of 12 men and 12 post-menopausal women by reverse transcriptase-polymerase chain reaction (RT-PCR) to examine whether or not and in which cell types aromatase was expressed. We also studied alternative use of multiple exon 1 of its gene and immunolocalization of 17beta-hydroxysteroid dehydrogenase type I (17beta-HSD I), which converts estrone produced by aromatase to estradiol, a biologically active estrogen. Aromatase immunoreactivity and mRNA hybridization signals and 17beta-HSD I immunoreactivity were all detected in smooth muscle cell (SMC) of the media and thickened intima, especially in SMC adjacent to an atheromatous plaque. The levels of aromatase mRNA were significantly higher in female cases than in male cases (P<0.05). The amount of aromatase mRNA was significantly higher in the specimens with fibroatheroma (P<0.05) than other lesions, and was also significantly higher in the cases utilizing 1c (I.3) or 1d (PII) of exon 1, i.e. gonadal types than those utilizing 1b (I.4), i.e. fibroblasts type as the promoter (P<0.01). These results suggest that estrone and estradiol are produced in SMC of the human aortic wall and that their production is mediated by aromatase and 17beta-HSD I, respectively. Moreover, it was suggested that aromatase overexpression, possibly as a result of alternative splicing, may play some roles in the development of atherosclerosis.
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PMID:Aromatase in atherosclerotic lesions of human aorta. 1185 Feb 9

A number of conditions related to sex-reversal in boys and men and precocious puberty in girls are caused by estrogen-secreting adrenal tumors. In these tumors, cytochrome P450 aromatase (aromatase) that is encoded in the CYP19 gene is expressed at high levels. To investigate the molecular mechanism of aromatase expression in these adrenal tumors, we characterized the activity, gene transcript and genomic promoter region of aromatase in the human adrenocortical carcinoma cell line H295R. Aromatase activity and the transcript of the CYP19 gene were highly up-regulated by forskolin, but not by dexamethasone. The results from exon I-specific reverse transcriptase (RT)-PCR and the transfection of reporter constructs suggested that promoter I.3 and promoter II were activated in H295R. Deletion and mutation analysis suggested that cAMP response element-like sequence (CLS) and steroidogenic factor-1 (SF-1) motif, were critical for the activation of promoter II. The results of this work should provide the basis for the molecular analysis of aromatase expression in adrenocortical cells.
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PMID:Forskolin up-regulates aromatase (CYP19) activity and gene transcripts in the human adrenocortical carcinoma cell line H295R. 1470 51

Mutations in the forkhead transcription factor gene FOXL2 are involved in ovarian failure, which occurs in human BPES syndrome. This syndrome presents a sexually dimorphic expression, specific to the ovary in several vertebrates. We cloned the open reading frame of chicken FOXL2 (cFoxL2) and studied cFoxL2 expression in developing gonads and during adulthood to examine the role of FOXL2 in ovarian differentiation and function in birds. The spatial and temporal dynamics of cFoxL2 and aromatase expression were analyzed in parallel by using real-time quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry in attempt to investigate the possible role of cFoxL2 in the regulation of aromatase. The expression patterns of cFoxL2 and aromatase transcripts were highly correlated during the sex-differentiation period (4.7-12.7 days of incubation). Aromatase and cFoxL2 proteins were colocalized in the medullar part of female gonads on embryonic day 14. Fourteen days after hatching, cFoxL2 protein was mainly detected in granulosa cells of developing follicles. In adult ovary follicular envelopes, apart from granulosa cells, cFoxL2 transcript and protein were detected at lower levels in theca cells where aromatase was present. A high level of cFoxL2 transcription was also observed in maturing and ovulated oocytes. Our results confirm that FoxL2 is an early regulator of ovarian development in birds and may be involved in aromatase transcription regulation.
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PMID:Isolation of chicken homolog of the FOXL2 gene and comparison of its expression patterns with those of aromatase during ovarian development. 1551 86

Steroid hormones have important modulatory effects on the hair follicle, but the mechanisms by which they regulate human hair growth are still poorly understood. It is now clear that there are two distinct estrogen receptors (estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta)) that bind 17beta-estradiol. Since the follicular dermal papilla is known to control hair growth, and steroid hormones regulate receptor and aromatase expression in other tissues, we tested the hypothesis that steroid hormones would similarly modulate estrogen receptor and/or aromatase expression in cultured dermal papilla cells derived from human hair follicles. Primary cultures of non-balding occipital and frontal scalp and beard dermal papilla cells (n = 10) were established. Immunocytochemical studies showed the expression of ERalpha in both the cytoplasm and nucleus, whereas ERbeta was confined to the nuclei. The cells derived from occipital scalp were also incubated for 24 hours with 10 nM of either 17beta-estradiol, estrone, testosterone, 5alpha-dihydrotestosterone, 5alpha-androstane-3alpha, 17beta-diol, 5alpha-androstane-3beta, 17beta-diol, or 100 nM tamoxifen or dexamethasone in phenol red-free, serum-free medium to measure the steady-state levels of ERalpha, ERbeta, and aromatase mRNA by semiquantitative reverse transcriptase-PCR. Although androgens and estrogens did not alter ERalpha mRNA levels, treatment with dexamethasone significantly reduced ERalpha levels to 38% of the untreated control. By contrast, ERbeta mRNA levels were unaffected by any steroid treatment. Furthermore, dexamethasone significantly stimulated the expression of aromatase mRNA approximately 9-fold. Aromatase activity, assayed by the tritiated water method, was stimulated in both frontal scalp and beard dermal papilla cell cultures by dexamethasone. These observations provide evidence for a glucocorticoid-dependent mechanism whereby the selective action of estradiol via ERbeta may be promoted. Additionally, upregulation of aromatase combined with downregulation of ERalpha provides a basis for selective action of estradiol produced locally by autocrine or paracrine mechanisms.
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PMID:The modulation of aromatase and estrogen receptor alpha in cultured human dermal papilla cells by dexamethasone: a novel mechanism for selective action of estrogen via estrogen receptor beta? 1669 Nov 99

In the present study, we determined the potential for post-transcriptional regulation of cytochrome P450 aromatase (Cyp19), cytochrome P450 side-chain cleavage (Cyp11a) and 17beta-hydroxysteroid dehydrogenase I (Hsd17b1) mRNA. Bovine granulosa cells were cultured in non-luteinizing conditions that permit long-term oestradiol secretion. Half-lives of mRNA were measured by Northern and/or reverse transcriptase (RT)-PCR after inhibition of gene transcription. In FSH-stimulated cells, the Cyp11a and Hsd17b1 mRNAs had half-lives greater than 12 h. The half-life of Cyp19 mRNA was significantly shorter at 3 h. The addition of the translation inhibitor cycloheximide to FSH-stimulated cells significantly increased Cyp19 mRNA half-life to approximately 12 h. Stimulation of cells with insulin resulted in Cyp19 mRNA half-life that was double (P<0.05) that in FSH-stimulated cells. We conclude that bovine Cyp19 mRNA is very labile under physiological conditions, and that Cyp19 expression is under hormonal control at a post-transcriptional level.
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PMID:Hormonal regulation of cytochrome P450 aromatase mRNA stability in non-luteinizing bovine granulosa cells in vitro. 1683 15

Estrogens produced by the placenta are pivotal in human pregnancy and parturition. Several hormones are involved in regulating estrogen production. Recently, the corticotrophin releasing hormone family of peptides has expanded and among the new members, urocortin 2 is expressed from human placenta. The aim of the current study was to determine urocortin 2 effects on estradiol secretion and cytochrome P450 aromatase mRNA levels and protein expression from cultured human trophoblast cells. Trophoblast cell cultures were treated with urocortin 2 and for comparison, corticotrophin releasing hormone, or urocortin 1 in the presence of estrogen precursors dehydroepiandrosterone-sulfate, androstenedione, and testosterone. Estradiol output was measured using enzyme-linked immunosorbent assay. Cytochrome P450 aromatase mRNA levels and protein expression were evaluated using reverse transcriptase-polymerase chain reaction and Western blot. Trophoblast cell cultures treated with increasing amounts of corticotrophin releasing hormone and urocortin 1 showed increased secretion of E2 in the presence of androstenedione. In the presence of urocortin 2, E2 output in cultures treated with dehydroepiandrosterone, androstenedione, and testosterone was consistently raised in a time and dose-dependent manner to maximum values at 24 hours. P450 aromatase mRNA levels and protein expression were upregulated by urocortin 2 in the presence of C19 precursors. The addition of antisauvagine-30, a corticotrophin releasing hormone-receptor-2 antagonist, significantly reversed urocortin 2 effects on E2 secretion and P450 aromatase expression. Our results suggest that urocortin 2 may play a role in the regulation of E2 production throughout pregnancy, thereby contributing to the placental regulation of key reproductive events in pregnancy maintenance and parturition.
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PMID:Urocortin 2 stimulates estradiol secretion from cultured human placental cells: an effect mediated by the type 2 corticotrophin-releasing hormone (CRH) receptor. 1941 23

The great majority of breast carcinomas arising in postmenopausal women are estrogen dependent or positive for estrogen receptor (ER) in carcinoma cells despite markedly low plasma or circulating estrogen concentrations. In these patients, biologically active estrogens are locally produced from circulating inactive steroids including adrenal androgens in an intracrine mechanism in the breast cancer tissues and confer estrogenic activities on carcinoma cells. A series of enzymes are involved in this intra-tumoral or in situ production of estrogens in breast carcinoma tissues but aromatase, a member of the cytochrome P450 family, is a key enzyme of estrogen production through conversion from circulating adrenal androgens in estrogen-dependent postmenopausal breast cancer. It then becomes important to identify the sites of this estrogen production. There has been, however, controversy regarding intra-tumoral localization of aromatase in breast carcinoma, especially whether intra-tumoral production of estrogens through aromatase occurs in carcinoma or stromal cells. The enzyme was demonstrated to be expressed in both carcinoma and stromal cells in breast carcinoma tissues on immunohistochemistry with a well-characterized mAb 677 and combined laser capture microdissection/qualitative reverse transcriptase-polymerase chain reaction. Intra-tumoral aromatase in both of these cell types was subsequently demonstrated to be induced by carcinoma-stromal interactions associated with carcinoma invasion in breast tissue. The signals through various nuclear receptors, especially estrogen-related receptor-alpha in carcinoma cells and liver receptor homologue-1 in adipocytes adjacent to carcinoma invasion, in conjunction with various cytokines and/or growth factors, play pivotal roles in this induction of intra-tumoral aromatase. This increased aromatase subsequently results in increased in situ estrogen concentrations of breast cancer. Aromatase inhibitors are currently established as the gold standard for the treatment for ER-positive breast carcinoma but resistance to the therapy still remains to be solved by other modes of suppression of intra-tumoral estrogen production.
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PMID:In situ estrogen production and its regulation in human breast carcinoma: from endocrinology to intracrinology. 1988 28

Estrogens produced as a result of intratumoral aromatization has been recently shown to play important roles in proliferation of human non-small cell lung carcinomas (NSCLC), but the details have remained largely unknown. Therefore, in this study, we evaluated the possible roles of intratumoral aromatase in NSCLCs as follows: (a) evaluation of intratumoral localization of aromatase mRNA/protein in six lung adenocarcinoma cases using laser capture microdissection combined with quantitative reverse transcriptase-PCR and immunohistochemistry; (b) examination of the possible effects of isolated stromal cells from lung carcinoma tissues on aromatase mRNA transcript expression in lung carcinoma cell lines (A549 and LK87) through a coculture system; and (c) screening of cytokines derived from stromal LK001S and LK002S cells using cytokine antibody arrays and subsequent evaluation of effects of these cytokines on aromatase expression in A549 and LK87. Both aromatase mRNA and protein were mainly detected in intratumoral carcinoma cells but not in stromal cells. Aromatase expression of A549 and LK87 was upregulated in the presence of LK001S or LK002S cells. Several cytokines such as interleukin-6 (IL-6), oncostatin M, and tumor necrosis factor-alpha, all known as inducible factors of aromatase gene, were detected in conditioned media of LK001S and LK002S cells. Treatment of both oncostatin M and IL-6 induced aromatase gene expression in A549 an LK87, respectively. These results all indicated that intratumoral microenvironments, especially carcinoma-stromal cell interactions, play a pivotal role in the regulation of intratumoral estrogen synthesis through aromatase expression in human lung adenocarcinomas.
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PMID:Intratumoral localization of aromatase and interaction between stromal and parenchymal cells in the non-small cell lung carcinoma microenvironment. 2071 45


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