Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.5 (RNase)
 17,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have shown that androgen receptor (AR) is expressed in granulosa cells of healthy, growing ovarian follicles in rats and primates. However, AR expression in the bovine ovary has not been examined. Therefore, a 346-base pair segment of the bovine AR was cloned and sequenced. Using a ribonuclease protection assay, AR expression was detected in total RNA from bovine ovarian cortex. Expression (absence or presence) of AR mRNA was detected by in situ hybridization in bovine ovarian cortex. Follicles (n = 32) were classified as follows: type 1 (1 layer of flattened granulosa cells), type 2 (1-1.5 layers of cuboidal granulosa cells), type 3 (2-3 layers of granulosa cells), type 4 (4-6 layers of cuboidal granulosa cells and formation of thecal layer), and type 5 (>6 layers of cuboidal granulosa cells, defined theca layer, and antrum formation). Frequency of AR mRNA expression increased (P < 0.001) as follicles entered the growing pool. Expression of AR mRNA was absent in type 1 follicles (n = 8), but present in the granulosa cells of 41% of type 2 follicles (n = 12). In types 3-5 follicles, AR mRNA expression was present in granulosa cells of 100% of follicles examined (n = 4, 4, and 4, respectively) and was greater than type 1 follicles (P = 0.002). These data provide evidence of AR mRNA expression in bovine follicles and suggest that AR mRNA increases during early follicle development.
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PMID:Androgen receptor mRNA expression in the bovine ovary. 1515 36

The 3'UTRs of mammalian HIF-1alpha and EGF mRNA contain several highly conserved AU-rich elements (ARE) known to control the turnover of labile mRNAs by binding ARE-binding proteins that regulate nucleocytoplasmic shuttling, translation, and degradation. Androgens regulate the level and subcellular shuttling of HuR, a major ARE-binding protein that stabilizes many ARE-mRNAs. Pull down of biotinylated 3'UTRs of HIF-1alpha or EGF enriches HuR on blots from Jurkat cell lysates 5-fold, and enriches the amount of RNase-protected biotinylated RNA that comigrates with HuR approximately 10-fold. Dihydrotestosterone treatment decreases the HuR-protected riboprobe pulled down from total Jurkat cell lysates by 30-40%, apparently reflecting shifts in HuR from the nucleus to the cytoplasm. Androgen treatment also changes the amount of HuR-protected riboprobe pulled down from a PC-3 clone expressing a functional androgen receptor. The shift in the amount of riboprobe bound by HuR suggests that androgen is up-regulating endogenous ARE-mRNAs that can compete for binding endogenous HuR. These changes in the shuttling and ARE-binding of endogenous HuR indicate that androgen can act posttranscriptionally to regulate ARE-mRNAs, including HIF-1alpha and EGF.
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PMID:Androgens regulate the binding of endogenous HuR to the AU-rich 3'UTRs of HIF-1alpha and EGF mRNA. 1532 78

Testosterone is known to act differentially on skeletal muscle from different regions. Two genes likely to mediate the testosterone effect are IGF-I, an important growth regulator acting in an autocrine and paracrine way, and androgen receptor (AR), as receptor density could account for differential muscle growth. Another muscle-specific gene that may play a role in differential muscle growth is myostatin, a member of the transforming growth factor-beta superfamily, shown to be a negative regulator of skeletal muscle mass. The objective of this study was to quantify and compare the expression of these three genes in two different skeletal muscles in sheep. East Friesian x Dorset-sired ram lambs from Dorset ewes were used in a 2 x 4 factorial experiment. Eighteen sets of twins were assigned to four age groups corresponding to 77, 105, 133, and 161 d of age, and one individual from each set was castrated at birth. Total RNA was extracted from samples of splenius (SP) and semitendinosus muscles collected at the time of slaughter. Insulin-like growth factor-I mRNA was measured using competitive reverse-transcription PCR. Androgen receptor and myostatin mRNA were measured by ribonuclease protection assay with standard curves. Weight of SP was greater than semitendinosus in rams compared with wethers at 105, 133, and 161 d (P = 0.05, P = 0.04, and P = 0.02, respectively). The difference in IGF-I mRNA levels between the two muscles was greater in rams than in wethers at 133 (P = 0.001) and 161 d (P = 0.014), and the difference in AR mRNA levels was greater in rams than in wethers at 105, 133, and 161 d (P = 0.002, P < 0.001, and P < 0.001, respectively), with greater abundance in the SP. No difference was found in myostatin mRNA level between the two muscles in rams and wethers at any age. These results suggest that locally produced IGF-I and the regulation of AR expression are important for sexually dimorphic muscle growth patterns.
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PMID:Effect of testosterone on insulin-like growth factor-I, androgen receptor, and myostatin gene expression in splenius and semitendinosus muscles in sheep. 1575 34

Androgens are known to regulate gene expression in the renal proximal tubule. Whether the distal parts of the nephron, in particular the cortical collecting duct (CCD), where sodium reabsorption is controlled tightly by aldosterone, are also targets for these hormones is unknown. Real-time PCR on rat isolated renal tubules showed that androgen receptor mRNA is not only, as expected, expressed in the proximal tubule, but also in the CCD. We examined the effects of adrenalectomy (ADX) plus castration and in-vivo administration of the active metabolite of testosterone, dihydrotestosterone (DHT), on the intrarenal expression of N-myc downstream regulated gene 2 (NDRG2), an early aldosterone-induced gene located specifically in the CCD. NDRG2 belongs to a newly identified family of differentiation-related genes; although the function of these genes remains elusive, regulation of NDRG1 by androgens has been suggested. Castration plus ADX increased NDRG2 expression (RNase protection assay) significantly in the whole kidney, and a single i.p. injection of DHT caused a significant decrease in NDRG2 expression 4 h afterwards (up to 24 h). Furthermore, real-time PCR on microdissected tubules revealed that the decrease in NDRG2 expression caused by DHT is restricted to the CCD. Thus, aldosterone and androgens have opposite effects on NDRG2 expression in the renal CCD. These results are the first demonstration of androgen-dependent gene regulation in the rat renal CCD.
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PMID:Expression of androgen receptor and androgen regulation of NDRG2 in the rat renal collecting duct. 1614 56

The objective of this study was to examine the expression of receptors for androgen, estrogen, and progesterone in the fetal sheep brain during the critical period for sexual differentiation. We isolated mRNA from the hypothalamus-preoptic area (HPOA), amygdala (AMYG), medulla (MD), frontal cortex (FCTX) and olfactory bulbs (OB) of fetal sheep that were delivered on day 64 of gestation. Using a ribonuclease protection assay and species-specific cRNA probes, we measured mRNA expression levels of androgen receptor (AR), estrogen receptor alpha (ERalpha) and progesterone receptor (PR). ERalpha and AR mRNA were expressed in all of the tissues tested and highest in the HPOA. PR mRNA was measured in HPOA and AMYG only and was significantly higher in male than in female fetuses. We conclude that the fetal brain is a target site for circulating steroid hormones. These data have implications for the steroid dependent development of sexually dimorphic brain functions in sheep.
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PMID:Expression of steroid hormone receptors in the fetal sheep brain during the critical period for sexual differentiation. 1687 81

The evidence is compelling for progesterone receptor (PR) expression in the primate corpus luteum during the menstrual cycle, based on three experimental approaches: (a) immunocytochemistry, (b) radioligand binding to steroid-depleted tissue, and (c) reverse transcription-polymerase chain reaction or ribonuclease protection assay. This information is providing the impetus for studies on possible receptormediated roles for progesterone to control periovulatory events (including follicle rupture and luteal development) and the functional lifespan of the corpus luteum. Similar experiments suggest that estrogen receptors are nondetectable in the corpus luteum. Thus, "classic" receptor-mediated actions of estrogen, such as promoting PR expression, are not apparent; rather, the midcycle surge of LH assumes the role of stimulating PR expression in luteinizing granulosa cells. The recent discovery of androgen receptor expression in primate luteal tissue should lead to studies on the heretofore unsuspected actions of androgens in the corpus luteum.
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PMID:Receptors for sex steroids in the primate corpus luteum New insight into gonadotropin and steroid action. 1840 87

In vitro tumor cell growth inhibitory and cytotoxic synergisms between a novel amphibian oocytic ribonuclease (ONCONASE)(ONC) and tamoxifen (TMX), lovastatin (LVT) and cisplatin (CDDP), have been observed in the human, estrogen and androgen receptor positive, chemotherapy-resistant NIH-OVCAR-3 ovarian carcinoma cell line. In view of the fact that the resistance to the available systemic chemotherapy represents one of the most important causes of treatment failure in patients with advanced ovarian cancer, the observed various forms of combination therapy synergisms suggest that these regimens could be tested in vivo, including human clinical trials. Particularly important are findings of significant synergistic tumor cell growth inhibitory and cytotoxic activities exerted by the combination of ONC with CDDP; NIH-OVCAR-3 cells are reportedly resistant to the latter. Of specific interest are the observed synergisms between ONC and TMX and between ONC and LVT, an inhibitor of the 3-hydroxy-3- methyl-glutaryl-CoA reductase which is a rate-limiting enzyme in the mevalonate/cholesterol synthesis pathway. A facilitation of apoptosis-induction by the drug combinations presently studied is discussed as a possible mechanism of the observed synergisms.
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PMID:Invitro synergism between a novel amphibian oocytic ribonuclease (onconase(r)) and tamoxifen, lovastatin and Cisplatin, in human ovcar-3 ovarian-carcinoma cell-line. 2158 16

Deregulated expression of circular RNAs (circRNAs) is associated with various human diseases, including many types of cancer. Despite their growing links to cancer, there has been limited characterization of circRNAs in metastatic castration-resistant prostate cancer, the major cause of prostate cancer mortality. Here, through the analysis of an exome-capture RNA-seq dataset from 47 metastatic castration-resistant prostate cancer samples and ribodepletion and RNase R RNA-sequencing of patient-derived xenografts (PDXs) and cell models, we identified 13 circRNAs generated from the key prostate cancer driver gene-androgen receptor (AR). We validated and characterized the top four most abundant, clinically relevant AR circRNAs. Expression of these AR circRNAs was upregulated during castration-resistant progression of PDXs. The upregulation was not due to global increase of circRNA formation in these tumors. Instead, the levels of AR circRNAs correlated strongly with that of the linear AR transcripts (both AR and AR variants) in clinical samples and PDXs, indicating a transcriptional mechanism of regulation. In cultured cells, androgen suppressed the expression of these AR circRNAs and the linear AR transcripts, and the suppression was attenuated by an antiandrogen. Using nuclear/cytoplasmic fractionation and RNA in-situ hybridization assays, we demonstrated predominant cytoplasmic localization of these AR circRNAs, indicating likely cytoplasmic functions. Overall, this is the first comprehensive characterization of circRNAs arising from the AR gene. With greater resistance to exoribonuclease compared to the linear AR transcripts and detectability of AR circRNAs in patient plasma, these AR circRNAs may serve as surrogate circulating markers for AR/AR-variant expression and castration-resistant prostate cancer progression.
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PMID:Circular RNAs add diversity to androgen receptor isoform repertoire in castration-resistant prostate cancer. 3140 97


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