Endocrinology, Vol 126, 2145-2152, Copyright © 1990 by Endocrine Society

ARTICLES

Interleukin-1 inhibits the ovarian steroid-induced luteinizing hormone surge and release of hypothalamic luteinizing hormone-releasing hormone in rats

PS Kalra, A Sahu and SP Kalra
Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville 32610.

Interleukin-1 (IL-1), a polypeptide cytokine secreted by activated macrophages, has been postulated as a chemical messenger between the immune and endocrine systems. IL-1-immunopositive neurons and fibers have been visualized in the human and rat hypothalamus, and IL-1 receptors are present in the rat brain. We have examined the effects of human recombinant IL-1 (alpha- and beta-subtypes) on LH release in vivo and hypothalamic LHRH release in vitro. Ovariectomized rats were primed with estradiol benzoate, and progesterone was injected 48 h later to elicit a LH surge in the afternoon. IL-1 alpha and IL-1 beta were injected either intracerebroventricularly (icv) via a preimplanted cannula in the third ventricle of the brain or iv. Systemic injection of IL-1 alpha or IL-1 beta (58.8 pmol at 1300 and 1500 h) failed to influence the afternoon LH surge seen in saline-injected control rats. However, IL-1 beta (1.76 pmol) administered icv at 1300 and 1500 h or a single icv injection at 1300 h blocked the progesterone-induced LH surge. Similar icv injections of IL-1 alpha also significantly suppressed the afternoon LH surge compared to that in saline-injected control rats. However, IL-1 alpha was relatively less effective than the beta-subtype, since the LH surge was detected in some rats. To ascertain whether suppression of the LH surge was due to inhibition of LHRH release, the medial basal hypothalamus-preoptic area of estradiol benzoate-progesterone-treated ovariectomized rats was incubated with and without IL-1. Both IL-1 alpha and IL-1 beta, at concentrations of 0.1 nM and higher, significantly suppressed LHRH release in vitro from the medial basal hypothalamus-preoptic area. In contrast, IL-1 (10 nM) was completely ineffective in suppressing LHRH release from the microdissected median eminence. These results demonstrated an overall inhibitory effect of icv IL-1 on the LHRH-LH axis and suggest that suppression of the steroid-induced LH surge by IL-1 may primarily be due to inhibition of LHRH release at hypothalamic sites located within the blood-brain barrier.

This article has been cited by other articles:

				H. Watanobe and Y. Hayakawa Hypothalamic Interleukin-1{beta} and Tumor Necrosis Factor-{alpha}, But Not Interleukin-6, Mediate the Endotoxin-Induced Suppression of the Reproductive Axis in Rats Endocrinology, November 1, 2003; 144(11): 4868 - 4875. [Abstract] [Full Text] [PDF]

				J. M. Kirkwood, C. Bender, S. Agarwala, A. Tarhini, J. Shipe-Spotloe, B. Smelko, S. Donnelly, and L. Stover Mechanisms and Management of Toxicities Associated With High-Dose Interferon Alfa-2b Therapy J. Clin. Oncol., September 1, 2002; 20(17): 3703 - 3718. [Abstract] [Full Text] [PDF]

				C. Y. Williams, T. G. Harris, D. F. Battaglia, C. Viguié, and F. J. Karsch Endotoxin Inhibits Pituitary Responsiveness to Gonadotropin-Releasing Hormone Endocrinology, May 1, 2001; 142(5): 1915 - 1922. [Abstract] [Full Text]

				J. J. Puder, P. U. Freda, R. S. Goland, M. Ferin, and S. L. Wardlaw Stimulatory Effects of Stress on Gonadotropin Secretion in Estrogen-Treated Women J. Clin. Endocrinol. Metab., June 1, 2000; 85(6): 2184 - 2188. [Abstract] [Full Text]

				D. F. Battaglia, H. B. Krasa, V. Padmanabhan, C. Viguié, and F. J. Karsch Endocrine Alterations That Underlie Endotoxin-Induced Disruption of the Follicular Phase in Ewes Biol Reprod, January 1, 2000; 62(1): 45 - 53. [Abstract] [Full Text]

				D. F. Battaglia, A. B. Beaver, T. G. Harris, E. Tanhehco, C. Viguié, and F. J. Karsch Endotoxin Disrupts the Estradiol-Induced Luteinizing Hormone Surge: Interference with Estradiol Signal Reading, Not Surge Release Endocrinology, June 1, 1999; 140(6): 2471 - 2479. [Abstract] [Full Text]

				E. Xiao, L. Xia-Zhang, A. Barth, J. Zhu, and M. Ferin Stress and the Menstrual Cycle: Relevance of Cycle Quality in the Short- and Long-Term Response to a 5-Day Endotoxin Challenge during the Follicular Phase in the Rhesus Monkey J. Clin. Endocrinol. Metab., July 1, 1998; 83(7): 2454 - 2460. [Abstract] [Full Text]

				D. F. Battaglia, J. M. Bowen, H. B. Krasa, L. A. Thrun, C. Viguie, and F. J. Karsch Endotoxin Inhibits the Reproductive Neuroendocrine Axis While Stimulating Adrenal Steroids: A Simultaneous View from Hypophyseal Portal and Peripheral Blood Endocrinology, October 1, 1997; 138(10): 4273 - 4281. [Abstract] [Full Text] [PDF]

				A. V. Turnbull and C. Rivier Inhibition of Gonadotropin-Induced Testosterone Secretion by the Intracerebroventricular Injection of Interleukin-1{beta} in the Male Rat Endocrinology, March 1, 1997; 138(3): 1008 - 1013. [Abstract] [Full Text] [PDF]