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The anti-gonadotropic effects of cytokines: the role of neuropeptides.
Domest Anim Endocrinol. 1998 Sep; 15(5):321-32.DA

Abstract

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.

Authors+Show Affiliations

Department of Physiology, University of Florida, College of Medicine, Gainesville 32610, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.
Review

Language

eng

PubMed ID

9785036

Citation

Kalra, P S., et al. "The Anti-gonadotropic Effects of Cytokines: the Role of Neuropeptides." Domestic Animal Endocrinology, vol. 15, no. 5, 1998, pp. 321-32.
Kalra PS, Edwards TG, Xu B, et al. The anti-gonadotropic effects of cytokines: the role of neuropeptides. Domest Anim Endocrinol. 1998;15(5):321-32.
Kalra, P. S., Edwards, T. G., Xu, B., Jain, M., & Kalra, S. P. (1998). The anti-gonadotropic effects of cytokines: the role of neuropeptides. Domestic Animal Endocrinology, 15(5), 321-32.
Kalra PS, et al. The Anti-gonadotropic Effects of Cytokines: the Role of Neuropeptides. Domest Anim Endocrinol. 1998;15(5):321-32. PubMed PMID: 9785036.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The anti-gonadotropic effects of cytokines: the role of neuropeptides. AU - Kalra,P S, AU - Edwards,T G, AU - Xu,B, AU - Jain,M, AU - Kalra,S P, PY - 1998/10/24/pubmed PY - 1998/10/24/medline PY - 1998/10/24/entrez SP - 321 EP - 32 JF - Domestic animal endocrinology JO - Domest Anim Endocrinol VL - 15 IS - 5 N2 - 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. SN - 0739-7240 UR - https://brain.unboundmedicine.com/medline/citation/9785036/The_anti_gonadotropic_effects_of_cytokines:_the_role_of_neuropeptides_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0739-7240(98)00030-7 DB - PRIME DP - Unbound Medicine ER -