Nicotine Acetylcgoline Receptor Expression and Nicotineinduced modulation of Testosterone(T) producton in rat leydig cells
作者单位：Population CouncilNow YorkNew York 10021 USA
会议名称：《2006年浙江省病理学术会议暨第三届中国国际淋巴造血系统疾病诊断及治疗新进展研讨会》
会议日期：1000年
学科分类：1001[医学-基础医学(可授医学、理学学位)] 100104[医学-病理学与病理生理学] 10[医学]
摘 要：It has been reported that neuronal signaling directly controls Leydig cell steroidogenic function. Neuronal pathways to the testis and to the vicinity of Leydig cells have been demonstrated, but neurotransmitter senstitivity in these cells has remained unclear. The objectives of the present study were to determine if acetylcholine receptors (AchRs) are expressed in Leydig cells. Progenitor, immature and adult Leydig cells were purified from 21-, 35-and 90-day-old male Sprague Dawley rats, respectively, and AchR messenger RNA levels were measured by DNA macro- arrays. The nicotinic-AchR subunits α1,α2,α3,α4,α5,α6,α7,β1,β2,Δ,γ,and σ,and muscarinic AchR M2 through M5 were all included in the analysis. Subunits α1,α5, α4, α6,β1, β2, and σ were detected above significant signal threshold levels. None of the muscarinic receptor forms were detected. Subunit α4 had the highest signal level: it was undetectable in progenitor Leydig cells and increased sharply during the transitions to immature and adult Leydig cell by up to 100 fold. Transcript levels for the enzyme acetylcholinseterase, which metabolizes Ach, were also abundant. Adult Leydig cells were cytotoxically eliminated from adult testes by administration of the drug ethylene dimethanesulfonate. This induced Leydig cell regeneration, and it was noted that a4 subunit expression was eliminated along with the Leydig cells and reappeared only after 35 days with the restoration of normal serum testosterone concentrations. Purified adult Leydig cells were treated with different concentrations of nicotine (10-7 to 10-3M) for 3 hours. Nicotine exerted a biphasic dose response for LH stimulated T production. Lower doses, 10-5M, increased T levels by 20% (control 141±5 vs.171±9ng/106cell·3hr), whereas higher doses,e.g., 10-3M,lowered T production by 50% (71±1ng/106cells·3hr). Therefore, at physiological concentrations of agonist, the AchR pathway is stimulatory. These data suggest that nicotinic AchR signaling may be