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

---

Query: EC:3.1.27.4 (ribonuclease)
6,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Because the distribution and hormonal regulation of the androgen receptor (AR) mRNA in brains and pituitaries of adult rhesus monkeys have not been studied, we cloned and sequenced a 329-base pair segment of the 5' coding region of the rhesus AR cDNA. Monkey AR cDNA was 99% identical with the human sequence and 96% homologous with the rat sequence. Using a ribonuclease protection assay, we studied the distribution and regulation of AR mRNA in brains and anterior pituitary glands of three groups of male rhesus monkeys: intact (n = 3), castrated (Cx, n = 4), and Cx treated with testosterone (n = 6). Serum testosterone levels of Cx males treated with testosterone differed significantly (p < 0.05) in the morning but not in the evening hours from those in intact controls. Serum LH concentrations were significantly suppressed (p < 0.05) in both morning and evening serum samples of testosterone-treated males compared to intact controls. We found the highest concentrations of AR mRNA in the medial basal hypothalamus, the bed nucleus of the stria terminalis, the medial preoptic area-anterior hypothalamus, and the lateral dorsomedial hypothalamus. Intermediate amounts were found in the septum and amygdala. Low amounts were found in the hippocampus, cingulate cortex, parietal cortex, and cerebellum. The anterior pituitary gland also contained a large amount of AR mRNA. Surprisingly, neither Cx for 3 wk nor Cx plus testosterone replacement for 3 wk significantly affected AR mRNA in any brain area or in the pituitary gland. The present study demonstrates that the effectiveness of testosterone as a regulator of LH secretion in male monkeys is not related to changes of AR mRNA in the brain or pituitary gland. It appears that AR mRNA in the monkey brain and pituitary gland is not regulated at the transcriptional level by androgen.
...
PMID:Androgen receptor messenger ribonucleic acid in brains and pituitaries of male rhesus monkeys: studies on distribution, hormonal control, and relationship to luteinizing hormone secretion. 1020 92

Targeted disruption of the mouse estrogen receptor-alpha gene (estrogen receptor-alpha knockout; ERKO) results in a highly novel ovarian phenotype in the adult. The ERKO mouse model was used to characterize ER alpha-dependent processes in the ovary. Visualization of the ovaries of 10-, 20-, and 50-day-old wild-type (WT) and ERKO mice showed that the ERKO phenotype developed between 20 and 50 days of age. Developmental progression through the primordial, primary, and antral follicle stages appeared normal, but functional maturation of preovulatory follicles was arrested resulting in atresia or in anovulatory follicles, which in many cases formed large, hemorrhagic cysts. Corpora lutea were absent, which also indicates that the normal biochemical and mechanical processes that accomplish ovulation were compromised. Northern and ribonuclease protection analyses indicated that ERKO ovary FSH receptor (FSHR) messenger RNA (mRNA) expression was approximately 4-fold greater than in WT controls. Ovarian LH receptor (LHR) mRNA expression was also higher in the ERKO animals. Cellular localization studies by in situ hybridization analysis of ERKO ovaries showed a high level of LHR mRNA expression in the granulosa and thecal layers of virtually all the antral follicles. Ribonuclease protection analyses showed that ovarian progesterone receptor and androgen receptor mRNA expression were similar in the two groups. These results indicated that ER alpha action was not a prerequisite for LHR mRNA expression by thecal or granulosa cells or for ovarian expression of progesterone receptor mRNA. Ovarian estrogen receptor beta (ER beta) was detected immunohistochemically, was sharply compartmentalized to the granulosa cells, and was expressed approximately equally in the ERKO animals and the WT controls. In contrast, ER alpha staining was present in the thecal cells but not the granulosa cells of the WT animals. The summary findings indicate that in the adult the major cause of the ERKO phenotype is high circulating LH interacting with functional LHR of the theca and granulosa cells. These features result in a failure of the normal maturational events leading to successful ovulation and luteinization and presumably involve both hypothalamic-pituitary and intraovarian mechanisms dependent upon ER alpha action. The presence of ER beta in the granulosa cells did not rescue the phenotype of the ovary.
...
PMID:Targeted disruption of the estrogen receptor-alpha gene in female mice: characterization of ovarian responses and phenotype in the adult. 1034 64

Genes that are regulated by androgens in the human prostate are believed to play an essential role in prostate physiology and they may also be involved in the proliferative response of prostate cancer cells to androgens. We used a cDNA subtraction approach to identify novel androgen-regulated transcripts in LNCaP cells that were exposed to 0.1 nM R1881 for 24 h. We report here that SPAK, a recently identified STE20/SPS1-related kinase that modulates p38 MAP kinase activity, exhibited increased expression in androgen-treated LNCaP cells. Androgen regulation of SPAK was both dose- and time-dependent. R1881-induced SPAK expression was completely abrogated by the antiandrogen casodex and by actinomycin D indicating that androgen induction of SPAK requires the androgen receptor and transcription. Cycloheximide caused a partial inhibition of R1881-induced SPAK expression which suggests that androgen induction of SPAK expression may require synthesis of additional proteins. Northern blot and ribonuclease protection assays demonstrated that SPAK is expressed at high levels in normal human testes and prostate, as well as in a number of breast and prostate cancer cell lines. These results identify SPAK, a member of a key cell signalling pathway, as an androgen-responsive gene in LNCaP cells. We hypothesize that SPAK may mediate androgen action in the normal and cancerous prostate gland.
...
PMID:Androgens induce expression of SPAK, a STE20/SPS1-related kinase, in LNCaP human prostate cancer cells. 1151 53

Testosterone is known to act differentially on skeletal muscle from different regions of the body. Two genes likely to mediate the testosterone effect are insulin-like growth factor I (IGF-I), an important growth regulator acting in an autocrine and paracrine way, and androgen receptor (AR), because 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 steady state expression of these three genes in two different skeletal muscles in sheep. Eleven Dorset rams were slaughtered after reaching puberty and total RNA was extracted from samples of semitendinosus and splenius muscles. Insulin-like growth factor I mRNA was measured using a competitive reverse-transcription-polymerase chain reaction. Androgen receptor and myostatin mRNA were measured by a ribonuclease protection assay (RPA) with standard curves. The means (attomoles/microg RNA) for splenius and semitendinosus muscles were 1.39 and 1.02 (SE = 0.14), 4.05 and 2.96 (SE = 0.24), and 4.30 and 3.85 (SE = 0.37) for IGF-I, AR, and myostatin, respectively. The difference between the two muscles was significant for IGF-I and AR mRNA levels with higher levels in the splenius but not significant for myostatin. Our results show that locally produced IGF-I and the regulation of AR expression may be important for sexually dimorphic muscle growth patterns.
...
PMID:Gene expression in sexually dimorphic muscles in sheep. 1216 55

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.
...
PMID:Androgen receptor mRNA expression in the bovine ovary. 1515 36

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.
...
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

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.
...
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.
...
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.
...
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


<< Previous 1 2

---