PMID- 9916024 OWN - NLM STAT- MEDLINE DCOM- 19990413 LR - 20190512 IS - 0006-3363 (Print) IS - 0006-3363 (Linking) VI - 60 IP - 2 DP - 1999 Feb TI - The inhibitory effect of intracerebroventricularly injected interleukin 1beta on testosterone secretion in the rat: role of steroidogenic acute regulatory protein. PG - 527-33 AB - Exposure to disease or injury often results in impaired reproductive activity accompanied by decreased testosterone levels. After immune activation, the cytokine interleukin 1-beta (IL-1beta) circulates in high concentrations, and its exogenous administration evokes many of the sequelae of immune activation. Previously, we have shown that the administration of this cytokine into the cerebral ventricles blunts hCG-stimulated testosterone secretion. This effect, though time-dependent, occurs before significant elevation of interleukin 6 in the peripheral bloodstream, does not depend on adrenal activation, and/or changes in LH concentrations, leading us to hypothesize a direct connection between the brain and testis. To explore this mechanism further, we isolated testicular tissue from rats treated intracerebroventricularly (icv) with vehicle or IL-1beta 30 or 90 min before they were killed. We found that in vivo cytokine treatment blunted ex vivo testosterone secretion in response to hCG, showing that the mechanism is independent of circulating cytokines. Though hCG binding was moderately reduced by icv IL-1beta in these preparations, the extent of this inhibition did not explain our observations. As the first acutely and hormonally regulated step in the biosynthesis of testosterone is the transfer of cholesterol into the inner mitochondrial membrane, which is mediated by steroidogenic acute regulatory (StAR) protein, we hypothesized that the rapid effects of icv IL-1beta on testicular responsiveness to hCG might be due to reduced levels of StAR. We report here that StAR protein was indeed reduced in Leydig cells isolated from rats treated in vivo with IL-1beta. Furthermore, treatment with a water-permeable form of cholesterol that bypasses the requirement for StAR partially restored hCG-stimulated testosterone secretion from testes isolated from rats treated icv with IL-1beta. Taken together, our data indicate that StAR plays a role in the suppression of testicular function evoked by central administration of IL-1beta. FAU - Ogilvie, K M AU - Ogilvie KM AD - The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, La Jolla, California 92037, USA. FAU - Held Hales, K AU - Held Hales K FAU - Roberts, M E AU - Roberts ME FAU - Hales, D B AU - Hales DB FAU - Rivier, C AU - Rivier C LA - eng GR - HD-13527/HD/NICHD NIH HHS/United States GR - HD-27571/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Biol Reprod JT - Biology of reproduction JID - 0207224 RN - 0 (Chorionic Gonadotropin) RN - 0 (Hydroxycholesterols) RN - 0 (Interleukin-1) RN - 0 (Phosphoproteins) RN - 0 (steroidogenic acute regulatory protein) RN - 17711-16-9 (22-hydroxycholesterol) RN - 3XMK78S47O (Testosterone) RN - 9002-67-9 (Luteinizing Hormone) RN - EC 1.14.14.19 (Steroid 17-alpha-Hydroxylase) SB - IM MH - Animals MH - Chorionic Gonadotropin/metabolism MH - Hydroxycholesterols/pharmacology MH - Injections, Intraventricular MH - Interleukin-1/*administration & dosage/pharmacology MH - Leydig Cells/physiology MH - Luteinizing Hormone/metabolism MH - Male MH - Phosphoproteins/*physiology MH - Rats MH - Rats, Sprague-Dawley MH - Steroid 17-alpha-Hydroxylase/metabolism MH - Testis/*metabolism MH - Testosterone/*metabolism EDAT- 1999/01/23 00:00 MHDA- 1999/01/23 00:01 CRDT- 1999/01/23 00:00 PHST- 1999/01/23 00:00 [pubmed] PHST- 1999/01/23 00:01 [medline] PHST- 1999/01/23 00:00 [entrez] AID - 10.1095/biolreprod60.2.527 [doi] PST - ppublish SO - Biol Reprod. 1999 Feb;60(2):527-33. doi: 10.1095/biolreprod60.2.527.