Inhibitory effect of neurogenic and immune stressors on testosterone secretion in rats.
OBJECTIVE
We investigated the ability of foot shocks, endotoxemia and turpentine-induced tissue injury, to interfere with luteinizing hormone (LH) and testosterone (T) secretion, and the putative role of beta-adrenergic, opiate- and corticotropin-releasing factor (CRF) receptors in these responses.


METHODS
Adult male rats were exposed to mild intermittent foot shocks for 1 h, administered endotoxin [lipopolysaccharide (LPS)] intravenously (i.v., 5 microg/kg), or injected with turpentine intradermally (i.m., 400 microl/kg), prior to injection with human chorionic gonadotropin (hCG, 1 U/kg i.v.). In some cases, antagonists to CRF, adrenergic or opiate receptors, or their vehicle were administered prior to the stressors. Levels of LH, T, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), adrenocorticotropin (ACTH) and/or corticosterone were measured in serial blood samples.


RESULTS
All three challenges significantly lowered basal LH and T levels and blunted the T response to hCG, though the magnitude of this inhibition was significantly (p < 0.01) smaller in shocked rats (42%), compared to animals injected with LPS (92%) or turpentine (78%). Shocks, LPS and turpentine all significantly stimulated ACTH and corticosterone release, and the magnitude and time course of these responses were also stressor specific. While turpentine only increased circulating IL-6 concentrations, shocks and LPS both significantly increased circulating TNF-alpha and IL-6 levels, but the effect of shocks was markedly smaller. Pretreatment with propranolol did not restore T responses, while naloxone produced small and inconsistent effects. However, the CRF antagonist Astressin B, which significantly prevented stressor-induced increase in circulating levels of ACTH and corticosterone, partially reversed the inhibitory effect of LPS on hCG-induced T release.


CONCLUSIONS
(1) Both neurogenic and systemic stressors lower basal plasma LH and T levels and blunt the T response to hCG. (2) LPS, whose ability to release ACTH and corticosterone was similar to that of shocks, but caused increases in circulating TNF-alpha and IL-6 levels that were significantly larger than those due to the other stressors, was the most potent inhibitor of the T response to hCG. (3) Neither beta-adrenergic nor opiate receptors play a major role in the ability of the stressors we used to inhibit T release.
Rivier
Catherine
C
Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, Calif. 92037, USA. crivier@salk.edu
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D004558:Electric Stimulation; D006066:Gonads / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D007107:Immune System / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000276:immunology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000276:immunology; D011957:Receptors, Opioid / Q000187:drug effects / Q000276:immunology; D013312:Stress, Physiological / Q000097:blood / Q000139:chemically induced / Q000276:immunology*; D013739:Testosterone / Q000097:blood / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D006063:Chorionic Gonadotropin; D015850:Interleukin-6; D009292:Narcotic Antagonists; D011943:Receptors, Adrenergic, beta; D018019:Receptors, Corticotropin-Releasing Hormone; D011957:Receptors, Opioid; D014409:Tumor Necrosis Factor-alpha; D013739:Testosterone; D000324:Adrenocorticotropic Hormone; D007986:Luteinizing Hormone; D003345:Corticosterone