| The anti-gonadotropic effects of cytokines: the role of neuropeptides. | |
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MedLine Citation:
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PMID: 9785036 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The inhibitory effect of inflammation and endotoxins on the secretion of reproductive hormones from the hypothalamo-pituitary axis is well documented. A comparison of the luteinizing hormone (LH) suppressing effects of several pro-inflammatory cytokines revealed that centrally administered IL-1 beta was the most potent inhibitor of pituitary LH secretion; interleukin (IL)-1 alpha and tumor necrosis factor (TNF) alpha were relatively less effective, whereas IL-6 was ineffective. This order of potency suggested that the anti-gonadotropic effects of an immune challenge are most likely attributable to the action of centrally released IL-1 beta, and this was supported by the demonstration that IL-1 beta suppressed hypothalamic luteinizing hormone releasing hormone (LHRH) release. We used a multifaceted approach to identify the afferent signals in the brain that convey immune messages to hypothalamic LHRH neurons. Pharmacological studies with specific antagonists of opioid receptor subtypes demonstrated that activation of the mu 1 receptor subtype was required to transmit the cytokine signal. Furthermore, icv IL-1 beta upregulated hypothalamic POMC mRNA and increased the concentration and release of beta-endorphin, the primary ligand of mu 1 receptors. We have obtained evidence that IL-1 beta also enhanced the gene expression and concentration of tachykinins, a family of nociceptive neuropeptides in the hypothalamus. Blockade of tachykinergic NK2 receptors attenuated IL-1 beta induced inhibition of LH secretion. Collectively, these results demonstrate that IL-1 beta, generated centrally in response to inflammation, upregulates the opioid and tachykinin peptides in the hypothalamus. These two groups of neuropeptides are critically involved in relaying the cytokine signal to neuroendocrine neurons and causing the suppression of hypothalamic LHRH and pituitary LH release. |
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Authors:
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P S Kalra; T G Edwards; B Xu; M Jain; S P Kalra |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S.; Review |
Journal Detail:
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Title: Domestic animal endocrinology Volume: 15 ISSN: 0739-7240 ISO Abbreviation: Domest. Anim. Endocrinol. Publication Date: 1998 Sep |
Date Detail:
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Created Date: 1998-12-30 Completed Date: 1998-12-30 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 8505191 Medline TA: Domest Anim Endocrinol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 321-32 Citation Subset: IM |
Affiliation:
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Department of Physiology, University of Florida, College of Medicine, Gainesville 32610, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cytokines / metabolism, pharmacology* Endotoxins / pharmacology Female Gene Expression Regulation Gonadotropin-Releasing Hormone / secretion Gonadotropins, Pituitary / antagonists & inhibitors*, secretion Humans Hypothalamo-Hypophyseal System / immunology, physiology Hypothalamus / metabolism* Interleukin-1 / metabolism, pharmacology Luteinizing Hormone / blood, secretion Male Neuropeptides / physiology* Pituitary-Adrenal System / immunology, physiology Rats Receptors, Neurokinin-2 / physiology Receptors, Opioid, mu / physiology |
| Grant Support | |
ID/Acronym/Agency:
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HD 11362/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Endotoxins; 0/Gonadotropins, Pituitary; 0/Interleukin-1; 0/Neuropeptides; 0/Receptors, Neurokinin-2; 0/Receptors, Opioid, mu; 33515-09-2/Gonadotropin-Releasing Hormone; 9002-67-9/Luteinizing Hormone |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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