Effect of a dopamine agonist on luteinizing hormone receptors, cyclic AMP production and steroidogenesis in rat Leydig cells
Abstract
Dopamine agonists are known to increase the incidence of Leydig cell hyperplasia/adenomas when administered to rats over periods of 1-2 years. We have examined the early changes in factors affecting luteinizing hormone (LH)-controlled signal transduction pathways and steroidogenesis in Leydig cells in vitro after chronic oral administration of one of these dopamine agonists, Mesulergine (CU327-085) (N-(1-6,dimethylergolin-8a-yl)-N',N'-dimethylsulphamide hydrochloride) to Sprague-Dawley (SD) rats. Eight-week-old rats were given this dopamine agonist (2 mg/kg body wt/day) in food for 1, 5, or 12 weeks. The Leydig cells from control and treated rats were purified by elutriation and density gradient centrifugation. The dopamine agonist treatment was found to decrease the specific binding of 125I-human chorionic gonadotrophin (hCG) binding to the Leydig cells: a decrease was detected as early as 1 week after treatment and was more pronounced after 5 and 12 weeks. This was found to be due to a decrease in the LH/hCG receptor numbers and not to a decrease in LH/hCG-receptor binding affinity. Both basal and LH-stimulated cAMP and testosterone production were also decreased; cAMP production was decreased by approximately 50% by all conc...Continue Reading
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