| Differential effects of central and peripheral administration of growth hormone (GH) and insulin-like growth factor on hypothalamic GH-releasing hormone and somatostatin gene expression in GH-deficient dwarf rats. | |
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MedLine Citation:
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PMID: 8102097 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The roles of GH and insulin-like growth factor-I (IGF-I) in the regulation of hypothalamic GH-releasing hormone (GRH) and somatostatin (SRIH) gene expression were investigated in the GH-deficient dwarf (dw) rat, in which endogenous feedback signals are lacking. Adult male and female dw rats were treated with GH or IGF-I by systemic (sc) administration or intracerebroventricular (icv) infusion, and hypothalamic GRH and SRIH mRNA were determined by Northern blotting and densitometric analysis. Systemic sc injection of rGH (75 micrograms every 12 h for 3 days) decreased GRH mRNA levels in both sexes. However, systemic sc injection of human IGF-I (150 micrograms every 12 h for 3 days) did not affect GRH mRNA levels in either sex despite significant stimulation of body weight gain. The use of a continuous sc infusion, which normalized serum IGF-I levels, and prolongation of the treatment period to 7 days also failed to change GRH mRNA levels. SRIH mRNA was unaffected by systemic administration of either GH or IGF-I. Continuous icv infusion of GH (1 microgram/h for 7 days) decreased GRH mRNA levels in both sexes, but did not alter SRIH mRNA levels. Continuous icv infusion of IGF-I (100 ng/h for 7 days) decreased GRH mRNA in both sexes. In contrast, SRIH mRNA levels were increased in both sexes. IGF-I decreased GRH mRNA levels at icv infusion rates of 100 and 300 ng/h and stimulated SRIH mRNA levels at infusion rates of 30 and 100 ng/h. Food intake was unaffected at these infusion rates. Changes in GRH and SRIH mRNA levels in response to systemic or central GH and IGF-I administration were similar in both sexes, except that the decrease in GRH mRNA levels produced by the icv infusion of IGF-I was greater in female than in male rats. The results provide evidence for a direct inhibitory feedback effect of GH in the central nervous system on the regulation of hypothalamic GRH gene expression that is independent of peripheral IGF-I. IGF-I feedback, in contrast, appears to originate with central nervous system-derived IGF-I and exhibits a stimulatory effect on SRIH mRNA as well as an inhibitory effect on GRH mRNA. |
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Authors:
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M Sato; L A Frohman |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Endocrinology Volume: 133 ISSN: 0013-7227 ISO Abbreviation: Endocrinology Publication Date: 1993 Aug |
Date Detail:
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Created Date: 1993-09-03 Completed Date: 1993-09-03 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 793-9 Citation Subset: AIM; IM |
Affiliation:
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Department of Internal Medicine, University of Cincinnati, College of Medicine, Ohio 45267. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Northern Cerebral Ventricles / drug effects Dose-Response Relationship, Drug Dwarfism / metabolism* Female Gene Expression / drug effects Growth Hormone / administration & dosage, deficiency, pharmacology* Growth Hormone-Releasing Hormone / genetics* Hypothalamus / drug effects, metabolism* Insulin-Like Growth Factor I / administration & dosage, pharmacology* Male RNA, Messenger / metabolism Rats Rats, Mutant Strains Somatostatin / genetics* |
| Grant Support | |
ID/Acronym/Agency:
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DK-30667/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/RNA, Messenger; 51110-01-1/Somatostatin; 67763-96-6/Insulin-Like Growth Factor I; 9002-72-6/Growth Hormone; 9034-39-3/Growth Hormone-Releasing Hormone |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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