Nitric oxide stimulates ACTH secretion and the transcription of the genes encoding for NGFI-B, corticotropin-releasing factor, corticotropin-releasing factor receptor type 1, and vasopressin in the hypothalamus of the intact rat.
We investigated the effect of the intracerebroventricular injection of the nitric oxide (NO) donor 3-morpholino-sydnonimine (SIN-1) on the release of adrenocorticotropin hormone (ACTH) and the neuronal response of hypothalamic neurons responsible for this release. Rats that were administered SIN-1 showed significant elevations in plasma ACTH levels, a response that was virtually abolished by antibodies against corticotropin-releasing factor (CRF) and significantly blunted by vasopressin (VP) antiserum. SIN-1 also upregulated heteronuclear (hn) transcripts for CRF and VP and messenger RNA (mRNA) levels for the immediate early gene NGFI-B and for CRF receptor type 1 (CRF-R(1)) in the parvocellular portion of the paraventricular nucleus (PVN) of the hypothalamus. Blockade of prostaglandin synthesis with ibuprofen did not alter the ACTH or the PVN response to SIN-1. The central nucleus of the amygdala and the supraoptic nucleus, regions that are involved in autonomic adjustments to altered cardiovascular activity, also responded to SIN-1 with elevated NGFI-B mRNA levels. However, the only change in mean arterial blood pressure caused by this NO donor was a transient and modest increase. To our knowledge, this is the first demonstration that in the intact rat NO stimulates the activity of PVN neurons that control the hypothalamic-pituitary-adrenal axis. It must be noted, however, that our results do not allow us to determine whether this effect was direct or mediated through PVN afferents. This study should help resolve the controversy generated by the use of isolated brain tissues to investigate the net effect of NO on hypothalamic peptide production.
Lee
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The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, California 92037, USA.
Kim
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Rivier
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D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000679:Amygdala / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D017781:Genes, Immediate-Early / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D007052:Ibuprofen / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D008981:Molsidomine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000494:pharmacology*; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D009928:Organ Specificity; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid / Q000235:genetics; D013495:Supraoptic Nucleus / Q000187:drug effects / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*; D014667:Vasopressins / Q000235:genetics*; D000099052:CRF Receptor, Type 1
D004268:DNA-Binding Proteins; D020030:Nitric Oxide Donors; C539820:Nr4a1 protein, rat; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; D014667:Vasopressins; D009569:Nitric Oxide; D000099052:CRF Receptor, Type 1; C002385:linsidomine; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D008981:Molsidomine; D007052:Ibuprofen