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:3.1.27.1 (RNase)
16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gonadotropin subunit mRNA levels rise after castration, coincident with a period of increased GnRH input to the pituitary. In addition to increased levels of gonadotropin mRNAs, we observed that the sizes of the alpha and LH beta mRNAs were increased after ovariectomy (OVX) of rats. To determine whether these changes occurred in the 5' (alternate transcriptional start site or splicing)- or 3' (altered polyadenylation)-end of the molecules, mRNAs were cleaved using oligonucleotide-directed RNase-H digestion, and the fragments were analyzed by Northern blot, using probes specific to the 5'- and 3'-segments of each transcript. After OVX, there was no change in the sizes of the 5'-segments of LH beta, FSH beta, and alpha-subunit mRNAs. However, the LH beta and alpha-subunit 3'-fragments were increased in size, indicating a shift to more adenylated forms of the LH beta and alpha transcripts. For FSH beta, the 3'-fragment bands were more diffuse than for LH beta or alpha-subunit, and no alteration in the lengths of FSH beta poly(A) tails were detected. A perifused pituitary cell system was used to determine whether pulses of GnRH were sufficient to cause modifications of polyadenylation. GnRH was administered as hourly 10-nM pulses for 4-12 h. Time-dependent increases in the sizes of LH beta and alpha-subunit mRNAs were observed in GnRH-treated cells compared to cells receiving no GnRH. Changes in the lengths of LH beta and alpha-subunit mRNAs were shown to be due to increased polyadenylation, and there was no observable change in polyadenylation of FSH beta mRNA. In addition, no changes were observed in the size of the 3'-fragments of PRL or beta-actin mRNAs. These data demonstrate that pulsatile GnRH administered in vitro elicits specific increases in the lengths of the LH beta and alpha-subunit mRNA poly(A) tails. Similar changes occur after OVX. Thus, in addition to transcriptional stimulation of the gonadotropin gene, GnRH modifies gonadotropin mRNAs at a posttranscriptional level.
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PMID:Pulsatile gonadotropin-releasing hormone modifies polyadenylation of gonadotropin subunit messenger ribonucleic acids. 134 79

Previous studies have shown that transferred hybrid constructs containing the PRL promoter are expressed specifically in rat pituitary (GH) cell lines. However, it is not yet clear which DNA region(s) is primarily responsible for expression directed by this promoter in pituitary cells. In the present studies we have examined the DNA sequences required for cell type-specific transcription of the rat PRL (rPRL) promoter either during transient expression in intact cells or in nuclear chromatin extracts. RNase protection and nuclear run-on transcription assays showed directly that a PRL-chloramphenicol acetyltransferase (CAT) construct containing about two kilobase-pairs of the rPRL promoter region (pPRL-CAT) is transcribed specifically in pituitary (GH3) cells. Analysis by transient expression in GH3 cells of pPRL-CAT and its 5' deletions showed that 1) deletion of sequences between positions -1957 and -958 did not significantly affect CAT activity; 2) the first 187 basepairs (bp) of the rPRL promoter directs full CAT activity; and 3) 98% of this activity is accounted for by rPRL DNA sequences between positions -187 and -113, containing two GH3 chromatin footprinting sites. Analysis in GH3 cell nuclear extracts showed that transcription of PRL-CAT constructs is unaffected by successive 5' deletions from position -1957 to -187, and that further deletion to -75 yielded only a moderate (approximately 2-fold) decrease in transcription.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Proximal rat prolactin promoter sequences direct optimal, pituitary cell-specific transcription. 274 60

Most of the growth-promoting effects of GH are mediated through insulin-like growth factor-I (IGF-I). Pituitary GH gene expression is, in turn, inhibited by IGF-I. Since rat pituitary tissue and GH3 pituitary tumor cells express both the GH and the IGF-I genes, we have attempted to clarify their potential interactions in the somatotroph by examining hormonal factors involved in the regulation of pituitary IGF-I gene expression. IGF-I mRNA was measured in GH3 cells by a solution hybridization/RNase protection assay, using riboprobes to differentially protect the IGF-I variant mRNAs arising by alternative splicing at both the 5' untranslated (UT) and 3' ends of the primary transcript. GH3 cells contained both class A and class C 5' UT variant mRNAs, with a relative abundance similar to that found in the liver. Sixty-five percent of the total IGF-I mRNA in GH3 cells was processed at the 3' end to IGF-Ia, and 35% to IGF-Ib mRNAs, whereas in the liver the proportions were 85% and 15%, respectively. GH3 cells grown in thyroid hormone-depleted medium for 4 days contained low levels of IGF-I mRNA. T3 and human (h) GH induced total IGF-I mRNA content in thyroid hormone-depleted cells, with both 5' and 3' alternative transcripts regulated coordinately, an effect that was maximal at 48-72 h. T3 stimulation of GH3 IGF-I mRNA over 48 h was dose dependent (0.01-5 nM). Similarly, hGH (0.5-10 micrograms/ml) evoked a dose-dependent induction of IGF-I mRNA in the thyroid hormone-deficient GH3 cells. The effects of T3 (5 nM) and hGH (10 micrograms/ml) on IGF-I mRNA were not additive. Furthermore, the effects of both T3 and hGH were selective for IGF-I mRNA, as neither of these treatments stimulated PRL mRNA, and treatment with hGH decreased GH3 cell GH mRNA content. This model does not discriminate whether T3 has an independent effect on IGF-I gene expression or if its action is mediated solely through induction of GH. In conclusion, IGF-I mRNA transcripts are present in GH3 cells and are modulated by T3 and GH. Local paracrine or autocrine interactions may, therefore, be involved in the feedback control of GH secretion.
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PMID:Pituitary insulin-like growth factor-I gene expression: regulation by triiodothyronine and growth hormone. 279 94

Forty-one human pituitary adenoma specimens were examined for the presence of estrogen receptor (ER) messenger ribonucleic acid and protein using a combination of ribonuclease protection assay, [3H] estradiol ([3H]E2) binding, and ER immunohistochemistry. ER messenger ribonucleic acid prevalence was high in PRL-immunoreactive tumors (2 of 2), moderate in GH/PRL tumors (2 of 5), and low or absent (0 of 4) in GH tumors. In the GH/PRL-immunostaining tumors, the presence of the ER was uniformly associated with elevated serum PRL levels. Among the gonadotropin-immunostaining tumors, 10 of 17 were ER positive; within this group, those with gonadotroph adenoma characteristics were ER positive, whereas those with null cell/oncocytic characteristics were ER negative. Of the tumors that did not immunostain for any known anterior pituitary hormones, 3 of 11 were ER positive. ER immunohistochemistry in 14 tumors revealed a 100% correlation with ribonuclease protection assay results, whereas [3H]E2 binding, determined in 9 tumors, showed an 87% correlation. In summary, it appears that PRL and a specific class of gonadotropin-immunostaining tumors (identifiable by specific characteristics on electron microscope) contain ER, whereas GH-immunostaining tumors are ER negative. ER expression in normal pituitary paralleled that in macroadenomas (GH, 2.3%; PRL, 50%; FSH, 70%; LH, 83%; TSH, 4%; ACTH, 1%). The ER-positive tumors represent a subset whose growth and secretory profiles may be influenced by the gonadal steroidal milieu or by pharmacological agents that affect E2 levels or ER function.
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PMID:Estrogen receptor expression in human pituitary: correlation with immunohistochemistry in normal tissue, and immunohistochemistry and morphology in macroadenomas. 751 90

Pituitary adenylate cyclase activating polypeptide (PACAP) is a new member of the secretin/glucagon/vasoactive intestinal peptide (VIP) family. It stimulates adenylate cyclase in cultured rat pituitary cells, which have PACAP-specific receptors and expression of pituitary hormones. Therefore, PACAP is considered as a hypophysiotropic hormone. If so, there might be a feedback regulatory mechanism between pituitary hormones and hypothalamic PACAP. In the present study, we used nuclear run-on and RNase protection assays to examine whether transcription of the PACAP gene in the rat hypothalamus would change after hypophysectomy. PACAP levels in the hypothalamus were also determined by radioimmunoassay. The transcriptional rate of the PACAP gene and PACAP mRNA content decreased 1 and 2 weeks after hypophysectomy. Radioimmunoassayable PACAP levels in the hypothalamus also decreased after hypophysectomy. These findings suggest that the reduced rate of PACAP gene transcription after hypophysectomy causes the decreased mRNA and peptide levels in the hypothalamus. Replacement with GH, PRL, T4, corticosterone, and testosterone significantly restored PACAP mRNA levels in hypophysectomized rats to those in control animals. The results suggest that feedback regulation takes place between pituitary hormones or pituitary-dependent factors and hypothalamic PACAP.
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PMID:Effect of hypophysectomy on pituitary adenylate cyclase activating polypeptide gene expression in the rat hypothalamus. 765 92

During pregnancy, marked hyperplasia of the pancreatic islet cells has been observed. This effect may be mediated by the pregnancy-associated peptide hormones, placental lactogen, PRL, and GH, which were previously shown to be mitogenic to beta-cells in vitro. To study whether the responsiveness of islet cells to these hormones is regulated on the receptor level, GH and PRL receptor gene expression was studied in pancreata from male rats and virgin, pregnant, and lactating female rats and in cultured islets and insulinoma cells (RIN-5AH) in response to various hormones. The mRNA levels were quantitated by ribonuclease protection assay, using probes specific for mRNA encoding, extracellular and intracellular domains of the GH receptor, and short and long forms of the PRL receptor, respectively. Specific transcripts for the GH receptor were present in pancreas, islets, and RIN-5AH cells. Furthermore, as previously observed in RIN-5AH cells, a predominant expression of the long form of PRL receptor vs. the short form was also found in pancreas and islet cells. Male and nonpregnant female pancreas did not differ significantly in their levels of GH and PRL receptor mRNAs. On day 14 of pregnancy, increases in both GH and PRL receptor mRNA levels were observed (1.7- and 2.4-fold, respectively), and a further increase occurred in late pregnancy (day 19), when GH and PRL receptor mRNA levels were 2.7- and 3.9-fold higher than those in the nonpregnant state. mRNA levels returned toward the basal level during lactation. In the cultured islets, PRL receptor mRNA levels were markedly increased by GH and PRL (3.5- and 6.5-fold, respectively) after exposure for 24 h, whereas estradiol and testosterone had modest stimulating effects (1.8- and 1.5-fold increases, respectively). Dexamethasone induced a 2.5-fold increase in GH receptor mRNA levels, and a weak stimulatory effect was also observed for progesterone. In RIN-5AH cells, the effect of dexamethasone on GH receptor mRNA was detectable after 2 h and maximal after 16 h. In contrast, the effects of GH and PRL on PRL receptor mRNA required 24-48 h of exposure. The effective doses were within the physiological ranges. In conclusion, these results show a differential hormonal regulation of GH and PRL receptor gene expression in the pancreatic islets, which may play a role in the adaptive beta-cell growth during pregnancy.
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PMID:Effects of sex and pregnancy hormones on growth hormone and prolactin receptor gene expression in insulin-producing cells. 836 59

We have investigated the effect of increasing gestational age and cortisol on prolactin receptor (PRLR) gene expression in the fetal sheep liver during late gestation. RNA was extracted from the liver of sheep fetuses between 90 and 144 days (d) gestation (n = 18) and after intrafetal infusion of either cortisol (2-2.5 mg cortisol i.v./24 h; n = 6) or saline (n = 6) between 109 and 116 d gestation. A ribonuclease protection assay for the mRNAs encoding the long (PRLR1) and short (PRLR2) forms of the PRLR was developed using an antisense RNA probe complementary to ovine PRLR2. There was a significant increase (p < 0.05) in the relative levels of liver PRLR1: GAPDH mRNA and PRLR2: GAPDH mRNA levels in fetal sheep between 90 and 144d gestation (PRLR1 mRNA: 90-95 d 0.6 +/- 0.1, 131-133 d 1.2 +/- 0.2, 141-144 d 3.6 +/- 0.5; PRLR2 mRNA: 90-95 d 0.7 +/- 0.1; 131-133 d 1.4 +/- 0.2, 141-144 d 3.0 +/- 0.4). The relative levels of liver PRLR1 and PRLR2: GAPDH mRNA levels were higher (p < 0.05) after cortisol administration (1.7 +/- 0.3 and 0.9 +/- 0.1 respectively) when compared with the saline infused group (0.7 +/- 0.1 and 0.5 +/- 0.1 respectively). We have demonstrated therefore that there is in increase in the levels of the mRNA encoding PRLR1 and PRLR2 in the fetal sheep liver during late gestation and that physiological increases in fetal cortisol stimulate PRLR1 and PRLR2 expression in the liver of the sheep fetus. These data suggest that fetal PRL may play a role in the growth and maturation of the fetal liver which occurs before birth.
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PMID:Hepatic prolactin receptor gene expression increases in the sheep fetus before birth and after cortisol infusion. 904 46

In this study, we have analyzed the developmental expression of the prolactin receptor (PRL-R) gene in the ewe mammary gland during pregnancy and lactation. Using Northern and slot-blot analysis and in situ hybridization, we showed that the level of PRL-R mRNA in mammary epithelial cells increased during the second half of pregnancy, decreased at the end of pregnancy, and remained relatively stable during lactation with a level above that observed at the beginning of pregnancy. As shown by RNase protection assay, the ratio of the long to the short form of the PRL-R mRNA was always above 1. This ratio increased between Day 70 of pregnancy and term and decreased progressively during lactation. The high level of PRL-R mRNA before the induction of alphaS1-casein gene expression suggests that PRL may be involved in the growth and development of the mammary gland. More precisely, the increase of the ratio of the long to the short form of the PRL-R during lactogenesis suggests that the latter form may have a dominant negative action in the activation of milk protein gene transcription. Thus the long/short-form ratio of the PRL-R may play a key role in the shift between growth and differentiation of the mammary gland.
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PMID:Developmental expression and localization of the prolactin receptor (PRL-R) gene in ewe mammary gland during pregnancy and lactation: estimation of the ratio of the two forms of PRL-R messenger ribonucleic acid. 960 66

PRL is synthesized by decidualized endometrial stromal cells from the midsecretory phase in a nonconception cycle and throughout pregnancy. The exact role of PRL in the human endometrium remains to be elucidated; however, the pattern of expression supports a role for PRL during implantation and placentation. This study investigated the site and pattern of expression of PRL receptors in the nonpregnant human endometrium. In situ hybridization and immunohistochemistry localized expression of the receptor in the glandular epithelium and a subset of stromal cells of the endometrium. As judged by the intensity of staining, expression of the receptor was dramatically up-regulated during the secretory phase. Expression of the PRL receptor gene in the endometrium from the secretory phase of the menstrual cycle was confirmed by ribonuclease protection assay using 50 micrograms total ribonucleic acid. Phosphorylation of Janus kinase-2 (JAK2), STAT1 (signal transducer and activator of transcription-1), and STAT5 proteins in response to PRL was investigated to establish the signaling pathway of PRL in the human endometrium. Endometrial tissue was collected during the secretory phase of the menstrual cycle and incubated in the presence of 100 ng/mL human PRL for 0, 5, 10, and 20 min. JAK2 phosphorylation was induced by PRL at 5 min, whereas STAT1 and STAT5 phosphorylation was apparent 20 min after stimulation with PRL. Immunohistochemistry localized the JAK/STAT proteins in the glandular epithelial cells and a subset of stromal cells, as was observed for the PRL receptor. Secretory phase stromal and glandular cells cultured separately and in the presence or absence of 100 ng/mL PRL confirmed the PRL-induced phosphorylation of JAK2/STAT proteins, at least in the glandular compartment. These studies demonstrate an up-regulation of expression of functional PRL receptors during the secretory phase of the menstrual cycle. Further, decidual PRL through a paracrine mechanism may influence glandular epithelial function/secretions and direct gene transcription through the JAK/STAT pathway. The target genes activated by PRL in the glandular epithelium of the nonpregnant human endometrium remain to be elucidated.
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PMID:Expression of functional prolactin receptors in nonpregnant human endometrium: janus kinase-2, signal transducer and activator of transcription-1 (STAT1), and STAT5 proteins are phosphorylated after stimulation with prolactin. 966 41

PRL expression in the human uterus is up-regulated during the mid to late secretory phase of the menstrual cycle. This coincides with up-regulation of the expression of the PRL receptor, which is localized primarily to the endometrial glandular epithelial cells. Recent data have demonstrated activation of the Jak (Janus kinase)/Stat (signal transducer and activator of transcription) signaling pathway in the secretory endometrium after stimulation with exogenous PRL. However, the target genes for the action of PRL on the endometrial epithelial cells have not been elucidated. In this study we have investigated the pattern/site of expression of the transcription factor interferon regulatory factor-1 (IRF-1) as well as the effect of exogenous PRL on the transcription of IRF-1 in the human endometrium during the mid to late secretory phase of the menstrual cycle. Expression of the IRF-1 gene was confirmed by RNase protection assays using a 260-bp homologous [alpha-32P]UTP-labeled IRF-1 complementary ribonucleic acid (RNA) probe and 10 microg total RNA extracted from human endometrium (n = 5) collected between days 19 and 26 of the menstrual cycle. Northern and Western blot analyses were conducted on secretory phase human endometrium (n = 3) using human [alpha-32P]dCTP-labeled IRF-1 complementary DNA and antihuman IRF-1 antibody. Expression of the IRF-1 gene in the secretory phase endometrium was encoded by a RNA transcript of approximately 2.1 kb and a protein of 48 kDa. Furthermore, expression of the IRF-1 gene in the secretory phase endometrium was localized by immunohistochemistry predominantly to the glandular epithelial cells as has been shown previously for the PRL receptor. To investigate the effect of PRL on expression of IRF-1, human endometrial biopsies (n = 3) collected between days 24-26 of the menstrual cycle were cultured in the presence of cycloheximide with or without 100 ng/mL human PRL for 2 and 4 h. Culture of endometrial tissue with PRL for 2 and 4 h resulted in 2.9 +/- 0.3-fold (P < 0.01) and 1.7 +/- 0.1-fold induction of expression of the IRF-1 gene, respectively. These data demonstrate the expression of the transcription factor IRF-1 in the glandular epithelium of the endometrium and its regulation by PRL during the secretory phase of the menstrual cycle. Previous observations of the temporal up-regulation of expression of both PRL and PRL receptors in the secretory human endometrium and their localization to the stromal and glandular compartments, respectively, suggest that endometrial PRL mediates transcription of the IRF-1 gene in a paracrine fashion.
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PMID:Localization of interferon regulatory factor-1 (IRF-1) in nonpregnant human endometrium: expression of IRF-1 is up-regulated by prolactin during the secretory phase of the menstrual cycle. 1056 82


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