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:3.1.26.9 (ribonuclease)
6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study describes the regulation of adrenal 3 beta-hydroxy-5-ene-steroid dehydrogenase/delta 5-delta 4-isomerase (3 beta HSD) expression and activity by ACTH and corticosterone, alone or in combination, in intact male and female rats as well as the effect of ACTH on 3 beta HSD expression and activity in the adrenals of hypophysectomized female animals. The effect of treatment on total 3 beta HSD mRNA levels was measured by dot blot hybridization using rat 3 beta HSD cDNA, while the specific regulation of type I and type II 3 beta HSD mRNAs was analyzed by ribonuclease protection assay. The concentration of 3 beta HSD protein was measured by Western blot, using cross-reacting antibodies raised against purified human placental 3 beta HSD, while 3 beta HSD enzymatic activity was measured by the conversion of [14C]dehydroepiandrosterone into [14C]androstenedione. The present data show that the trophic effect of ACTH on male and female rat adrenals is accompanied by increases in total 3 beta HSD mRNA, enzymatic activity, and protein content. Hypophysectomy, on the other hand, causes a marked decrease in 3 beta HSD mRNA levels and enzymatic activity, which is completely reversed by administration of ACTH. On the other hand, corticosterone treatment results in a marked inhibition of 3 beta HSD mRNA levels, enzymatic activity, and protein content in intact animals; this effect is probably mediated by a decrease in ACTH secretion. The present data show that ACTH and corticosterone, via its inhibitory action on ACTH secretion, have potent and opposite effects on the expression of two 3 beta HSD genes in the rat adrenal; a parallel effect is observed on both type I and II 3 beta HSD. Such data suggest that 3 beta HSD could well play a major role in the regulation of steroid formation in the adrenal cortex.
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PMID:Regulation of adrenal 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase expression and activity by adrenocorticotropin and corticosterone in the rat. 165 93

Human fetal adrenal growth after midgestation is very rapid and appears to be dependent upon pituitary adrenocorticotropin (ACTH) in vivo. We hypothesized that the regulation of fetal adrenal growth by ACTH is mediated by ACTH-stimulated local growth factor production. As we have found basic fibroblast growth factor (bFGF) to be a potent mitogen for human fetal adrenal cells in culture, we conducted studies to determine whether bFGF is synthesized by the human fetal adrenal gland and whether bFGF gene expression in primary cultures of human fetal adrenal cells is regulated by ACTH. Bioassayable bFGF-like activity was detected in extracts of whole human fetal adrenal glands and primary cultures of human fetal adrenal cells. Northern blot analysis of total RNA from whole human fetal adrenal glands revealed a characteristic 7-kilobase bFGF mRNA, indicating that the fetal adrenal bFGF bioactivity was most likely due to local synthesis. Slot blot and ribonuclease protection analysis showed that bFGF mRNA was present in very low amounts in total RNA from primary cultures of unstimulated human fetal adrenal cells but was increased 2- to 3-fold in cells exposed to 10 nM ACTH-(1-24) or 1 mM 8-bromoadenosine 3',5'-cyclic monophosphate for 24 hr. bFGF mRNA was localized to adrenocortical cells and not fibroblasts by in situ hybridization. bFGF mRNA was barely detectable in unstimulated cells, whereas it was markedly increased in cells exposed to either ACTH or 8-bromoadenosine 3',5'-cyclic monophosphate. These data support our hypothesis that the regulation of human fetal adrenal growth by ACTH at midgestation may be mediated by the stimulation of local growth factor production, and we suggest that bFGF may play a major role in this process.
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PMID:Basic fibroblast growth factor expression is regulated by corticotropin in the human fetal adrenal: a model for adrenal growth regulation. 171 Dec 31

Previous studies have shown that a neutral metallo-endopeptidase purified from rat kidney degrades the B chain of insulin, glucagon, ACTH and, at a markedly slower rate, the A chain of insulin. In contrast the enzyme does not attack native insulin, oxytocin, vasopressin, ribonuclease, albumin or denatured hemoglobin. The current studies demonstrate that the neutral peptidase also degrades the isolated C-peptide of proinsulin and cleaves certain peptide bonds in and near the C-peptide moiety of native proinsulin. Time courses of the formation of fluorescamine-reactive material during digestion of proinsulin and isolated C-peptide with the peptidase were identical. However, structural analysis of the peptidase-digested proinsulin showed that the enzyme does not convert proinsulin to insulin but that the peptidase cleaves one bond, Tyr26-Thr27, in the B chain moiety and five bonds in the C-peptide moiety, producing four split proinsulins. One of the split proinsulins is des-octacosa-peptide (27-54) porcine proinsulin or des-tetracosapeptide (27-50) bovine proinsulin. Each is a derivative of the insulin molecule having an extension of nine residues (ten residues in the case of the derivative from bovine proinsulin) at the N-terminus of A chain and lacking four residues at the C-terminus of B chain. This two chain derivative retains full immunoreactivity with insulin antibodies and exhibits 2.4-times more biological activity (promotion of glycogenesis in primary cultured hepatocytes) than proinsulin and about two-thirds the activity of insulin.
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PMID:Degradation of proinsulin and isolated C-peptide by rat kidney neutral metallo-endopeptidase. 702 23

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

The expression of three somatostatin receptor subtypes, SSTR3, SSTR4, and SSTR5, was evaluated in 33 pituitary tumor specimens. SSTR3 expression was studied by reverse transcription coupled to polymerase chain reaction, whereas SSTR4 and SSTR5 expression was determined by ribonuclease protection assay. SSTR3 was expressed in 6 of 7 GH-secreting tumors, all 8 clinically nonfunctioning tumors, all 3 prolactinomas, and 1 of 2 ACTH-secreting tumors tested. Eight nonfunctioning adenomas had undetectable messenger ribonucleic acid levels of SSTR4, and only 1 of them expressed SSTR5. SSTR4 expression was also undetectable in 11 GH-secreting tumors, 3 prolactinomas, and 1 ACTH-secreting tumor tested. In contrast, SSTR5 was highly expressed in 10 of 11 GH-secreting adenomas and 1 prolactinoma. Two prolactinomas and 1 ACTH-secreting tumor had low levels of expression of SSTR5. The widespread pituitary adenoma expression of SSTR3, regardless of hormonal secretory type, suggests that SSTR3 might be involved in a somatostatin action(s) other than GH or TSH regulation. SSTR5 is expressed predominantly in mammosomatotroph-derived tumors, suggesting that this receptor subtype may be an important determinant of GH secretion in acromegaly.
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PMID:Expression of three somatostatin receptor subtypes in pituitary adenomas: evidence for preferential SSTR5 expression in the mammosomatotroph lineage. 752 50

The melanocortin (MC) peptides mediate a diverse spectrum of biological activities in both the central nervous system and peripheral tissues by interacting with specific guanine nucleotide binding (G protein)-coupled receptors. Previously, four human melanocortin receptor subtypes have been cloned and characterized. In this study, we have isolated mouse complementary DNA (cDNA) and human genomic clones encoding a fifth melanocortin receptor subtype, MC5. Melanocortin peptide stimulation of human MC5, transiently expressed in COS1 cells, results in activation of adenylate cyclase with the following rank order of potency: [Nle4, D-Phe7]-alpha-MSH (melanocyte stimulating hormone) > ACTH (1-24) (adrenocorticotropic hormone) > alpha-MSH > beta-MSH > gamma-MSH. Northern blot hybridization, ribonuclease protection, and reverse transcription/polymerase chain reaction assays indicate that mouse MC5 mRNA is most abundant in skeletal muscle and brain. Lower but detectable levels of MC5 mRNA are also found in RT2-2 retinal neuronal cells, lung, testis, spleen, heart, kidney, and liver.
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PMID:Cloning, expression, and tissue distribution of a fifth melanocortin receptor subtype. 773 52

The possible roles of certain oncogenes in the development of pituitary tumors has not been investigated. We have examined the expression of c-myc, c-fos, and c-myb in a number of human pituitary tumors by ribonuclease protection assays, as these oncogenes have been implicated to have roles in the pathogenesis of other human tumors (12, 13, 15, 16). In several tumors examined (9 of 30) c-myc was expressed at levels 4-9 times greater than the level detected in normal postmortem pituitary. Although a larger percentage of negative immunohistochemical-staining tumors overexpressed c-myc, c-myc over-expression was not limited to this group of tumors. c-Fos was overexpressed in 1 of 30 tumors examined at a level 5.8-fold higher than that detected in normal postmortem pituitary. This tumor stained positive for ACTH by immunohistochemistry and was considered highly aggressive, demonstrating invasion beyond the sella turcica; however, when other ACTH-staining and invasive pituitary tumors were examined, no abnormality in the expression of c-fos was detected. In 30 tumors, c-myb was expressed at approximately the same level as that detected in normal postmortem pituitary. We conclude that c-myc is overexpressed in a subgroup of pituitary tumors and that this overexpression occurs broadly among the different groups of immunohistochemical-staining tumors. c-Fos overexpression appears to be much less common in pituitary tumors and does not necessarily correlate with the ability of the tumor to become invasive. c-Myb does not appear to have a role in the pathogenesis of pituitary tumors.
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PMID:c-myc, c-fos, and c-myb gene expression in human pituitary adenomas. 802 38

Gene expression in mammalian cells can be suppressed by oligonucleotides complementary to the target mRNA. This strategy was explored as a means of arresting translation of the prohormone precursor proopiomelanocortin (POMC), used as a model system of peptide messengers that are synthesized and released from endocrine and neuronal cells. The synthesis of the POMC-derived peptides adrenocorticotropin (ACTH) and beta-endorphin (beta-END) was markedly reduced by an oligodeoxynucleotide (ODN) complementary to a region of beta-END mRNA in AtT-20 cells, which retain many of the differentiated phenotypes of corticotrophs; this treatment did not affect the steady-state levels of POMC mRNA. Antisense ODN was stable in cell culture medium for 24 h, and cellular uptake was low (approximately 2.5% of the added ODN); however, the intracellular levels of the ODN were sufficient to form a ribonuclease-resistant duplex with complementary cellular mRNA. Addition of ODN to the cell culture did not affect the cellular levels of chromogranin A-(264-314)/pancreastatin or cell viability and proliferation, as evidenced by bromodeoxyuridine incorporation and ornithine decarboxylase activity. Microinfusion of the antisense ODN in the rat hypothalamic arcuate nucleus, where the majority of POMC-positive brain perikarya are located, significantly reduced ACTH- and beta-END-immunopositive neurons, and antisense ODN-treated rats showed substantially less of the grooming behavior usually observed in a novel environment.
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PMID:Inhibition of proopiomelanocortin expression by an oligodeoxynucleotide complementary to beta-endorphin mRNA. 805 59

Recent studies have shown that corticotropin releasing factor (CRF) stimulates c-fos gene expression in the AtT-20 corticotroph cell line, and that overexpression of c-Fos results in activation of POMC gene transcription. Since transactivation by c-Fos requires dimerization with a Jun family member to form the active transcription factor AP-1, we have examined the expression of multiple fos and jun related genes and have correlated their expression with AP-1 DNA binding activity in AtT-20 nuclear extracts after stimulation with CRF. Although basal expression of c-fos mRNA was extremely low, it was rapidly and transiently stimulated in AtT-20 cells following administration of either constant or a single pulse of CRF. In contrast, basal expression of c-jun mRNA was slightly higher and underwent little or no change in response to CRF. Specific ribonuclease protection analysis showed that in addition to c-fos, mRNA transcripts encoding fos B and jun B were rapidly stimulated in response to CRF, though levels of induced fos B mRNA were 20-40 times lower than c-fos or jun B, respectively. Gel shift analysis demonstrated that CRF caused a sustained increase in AP-1 DNA binding to both a canonical AP-1 element as well as to the POMC exon-1 AP-1 site. Studies with specific antisera directed against c-Fos revealed that although no c-Fos could be detected in AP-1 complexes in basal cell extracts, c-Fos became a prominent component of AP-1 following CRF stimulation, reaching maximal levels by 4 h. Despite the fact that AP-1 DNA binding activity remained elevated for at least 24 h after CRF, c-Fos was most prominent during the early phase of the response. Similarly, JunB was shown to be a major component of AP-1 DNA binding activity in CRF-stimulated AtT-20 nuclear extracts that persisted for at least 24h after stimulation. Despite the obvious induction of fos B mRNA in response to CRF, FosB protein was not detected in DNA bound AP-1 complexes. These data demonstrate that CRF is a potent stimulus for corticotroph expression of c-fos, jun B and fos B, and suggest that the subsequent increase in AP-1 may play a role in activation of gene expression and/or as a modulator of glucocorticoid receptor function.
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PMID:CRF stimulates expression of multiple fos and jun related genes in the AtT-20 corticotroph cell. 879 51

Melanocortins (alphaMSH and ACTH-related peptides) influence the physiological functions of certain peripheral organs, including exocrine and endocrine glands. This study was designed to determine the identity and anatomical localization of the melanocortin receptors (MC-R) expressed in these organs in the rat. MC5-R messenger RNA was found in exocrine glands, including lacrimal, Harderian, preputial, and prostate glands and pancreas, as well as in adrenal gland, esophagus, and thymus, as demonstrated by ribonuclease protection assays. In exocrine glands, MC5-R messenger RNA expression was restricted to secretory epithelia. MC-R protein was likewise present in secretory epithelia of exocrine glands, as determined by 125I-labeled [Nle4,D-Phe7]alphaMSH ([125I]NDP-MSH) binding and autoradiography in tissue sections. Specific [125I]NDP-MSH binding was also observed in adrenal cortex, thymus, spleen, and esophageal and trachealis muscle. MC receptors in these sites are accessible to circulating MC-R agonists in vivo, as specific binding of [125I]NDP-MSH was observed in exocrine and adrenal glands after systemic injection in vivo. Taken together, these findings show that the MC5 receptor is commonly and selectively expressed in exocrine glands and other peripheral organs. Based on these findings and compelling evidence from other studies, a functional coherence is suggested between central and peripheral actions of melanocortins and melanocortin receptors in physiological functions, including thermoregulation, immunomodulation, and sexual behavior.
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PMID:Expression of melanocortin-5 receptor in secretory epithelia supports a functional role in exocrine and endocrine glands. 956 44


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