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Ligand Pharmaceuticals (K.O.), Department of Pharmacology, San Diego, California 92121; and The Clayton Foundation Laboratories for Peptide Biology (C.R.), The Salk Institute, La Jolla, California 92037
Address all correspondence and requests for reprints to: Catherine Rivier, The Clayton Foundation Laboratories for Peptide Science, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, California 92037. E-mail: crivier{at}salk.edu
The present work extends our previous report that the
intracerebroventricular (icv) injection of interleukin-1ß (IL-1ß,
80 ng) significantly blunted the testosterone response to 1 U/kg human
CG (hCG), an effect that we attributed to the stimulation of inhibitory
pathways connecting the hypothalamus to the testes. Systemic
blockade of prostaglandin-dependent pathways with ibuprofen
(
-methyl-4-[2-methyl-propyl]benzeneacetic acid; sodium salt),
which did not, in itself, alter the stimulatory effect of hCG on
testosterone release in control rats, modestly, but significantly
(P < 0.05) reversed the inhibitory influence of
IL-1ß. In contrast, blockade of brain receptors for CRF was unable to
alter the effect of IL-1ß, as were lesions of the ventromedial
hypothalamic nucleus, a brain area implicated in the control of ovarian
function. Blockade of ß-adrenergic receptors significantly prevented
the decrease in testicular responsiveness induced by the icv injection
of IL-1ß. Finally, the central injection of the ß-adrenergic
agonist isoproterenol, as well as that of norepinephrine, mimicked the
ability of icv IL-1ß to blunt testicular secretory activity and
produced a marked (P < 0.01) decrease in the
response to hCG within 5 min of their administration.
We propose that the explanation that best fits our findings is that the icv injection of IL-1ß activates a neural, catecholamine-dependent pathway that connects the brain and the testes independently of the pituitary.
This article has been cited by other articles:
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  D. J. Selvage, L. Parsons, and C. Rivier Role Played by Brainstem Neurons in Regulating Testosterone Secretion via a Direct Neural Pathway between the Hypothalamus and the Testes Endocrinology, June 1, 2006; 147(6): 3070 - 3075. [Abstract] [Full Text] [PDF]
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M. Herman and C. Rivier Activation of a Neural Brain-Testicular Pathway Rapidly Lowers Leydig Cell Levels of the Steroidogenic Acute Regulatory Protein and the Peripheral-Type Benzodiazepine Receptor while Increasing Levels of Neuronal Nitric Oxide Synthase Endocrinology, January 1, 2006; 147(1): 624 - 633. [Abstract] [Full Text] [PDF]
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S. Lee and C. Rivier Role Played by Hypothalamic Nuclear Factor-{kappa}B in Alcohol-Mediated Activation of the Rat Hypothalamic-Pituitary-Adrenal Axis Endocrinology, April 1, 2005; 146(4): 2006 - 2014. [Abstract] [Full Text] [PDF]
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D. R. Simorangkir, S. Ramaswamy, G. R. Marshall, and T. M. Plant In the Adult Male Rhesus Monkey (Macaca mulatta), Unilateral Orchidectomy in the Face of Unchanging Gonadotropin Stimulation Results in Partial Compensation of Testosterone Secretion by the Remaining Testis Endocrinology, November 1, 2004; 145(11): 5115 - 5120. [Abstract] [Full Text] [PDF]
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D. J. Selvage, S. Y. Lee, L. H. Parsons, D. O. Seo, and C. L. Rivier A Hypothalamic-Testicular Neural Pathway Is Influenced by Brain Catecholamines, But Not Testicular Blood Flow Endocrinology, April 1, 2004; 145(4): 1750 - 1759. [Abstract] [Full Text] [PDF]
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D. J. Selvage and C. Rivier Importance of the Paraventricular Nucleus of the Hypothalamus as a Component of a Neural Pathway between the Brain and the Testes that Modulates Testosterone Secretion Independently of the Pituitary Endocrinology, February 1, 2003; 144(2): 594 - 598. [Abstract] [Full Text] [PDF]
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S. Lee, R. Miselis, and C. Rivier Anatomical and Functional Evidence for a Neural Hypothalamic-Testicular Pathway that Is Independent of the Pituitary Endocrinology, November 1, 2002; 143(11): 4447 - 4454. [Abstract] [Full Text] [PDF]
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 K. M. Ogilvie, K. Held Hales, M. E. Roberts, D. Buchanan Hales, and C. Rivier The Inhibitory Effect of Intracerebroventricularly Injected Interleukin 1ß on Testosterone Secretion in the Rat: Role of Steroidogenic Acute Regulatory Protein Biol Reprod, February 1, 1999; 60(2): 527 - 533. [Abstract] [Full Text] [PDF]
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