Ghosh D, Chaudhuri A, Biswas N M, Ghosh P K
Department of Physiology, University Colleges of Science and Technology, Calcutta University, India.
Life Sci. 1990;46(2):127-37. doi: 10.1016/0024-3205(90)90045-s.
The present study was undertaken to evaluate the effects of lithium, an antimanic drug, on steroidogenic and gametogenic functions of testis in the laboratory rat. Adult male rats of Wistar strain maintained under standard laboratory conditions (L:D, 14h:10h), were injected (S.C) with lithium chloride at the dose of 0.1 mg, 0.2 mg and 0.4 mg/100 g body weight/day for 21 days. All the treated animals along with the vehicle treated controls were sacrificed 24 hours after the last injections. Testicular steroidogenic activity was evaluated by measuring the activities of two steroidogenic key enzymes, delta 5-3 beta hydroxysteroid dehydrogenase (delta 5-3 beta-HSD) and 17 beta hydroxysteroid dehydrogenase (17 beta-HSD). Gametogenic capacity was determined by counting the number of germ cells at stage VII of seminiferous cycle. Plasma levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL) and testosterone (T) were measured by radioimmunoassay (RIA). Administration of lithium chloride at a dose of 0.1 mg/100 g body wt. for 21 days led to insignificant changes of plasma FSH, LH, PRL and T along with unaltered activities of testicular delta 5-3 beta-HSD, 17 beta-HSD activities and gametogenesis. In contrast, 0.2 mg of lithium treatment for 21 days causes a significant reduction of plasma FSH (P less than 0.01), LH (P less than 0.001), PRL (P less than 0.001) and T (P less than 0.001) along with inhibition of testicular delta 5-3 beta-HSD activity (P less than 0.01) and 17 beta-HSD activity (P less than 0.001). Gametogenic activity does not exhibits any significant reduction in the number of preleptotene spermatocytes (PLSc) and midpachytene spermatocytes (mPSC) while significant reduction in the number of spermatogonia A (Asg) (P less than 0.01) and Step 7 spermatids (7Sd) (P less than 0.001) were observed at stage VII of seminiferous cycle when compared to control. The degree of detrimental effects of lithium on testicular activity became more prominent at the dose of 0.4 mg/100 g body wt. The results of our experiments suggest that lithium administration might be associated with significant adverse effects on testicular activities. Furthermore, since hormonal changes and altered gametogenic activities were evident when plasma lithium concentration was below or within the therapeutic range, our data may have some potential clinical implications.
本研究旨在评估抗躁狂药物锂对实验大鼠睾丸类固醇生成和配子生成功能的影响。将维持在标准实验室条件（光照：黑暗，14小时：10小时）下的成年雄性Wistar大鼠，按0.1毫克、0.2毫克和0.4毫克/100克体重/天的剂量皮下注射氯化锂，持续21天。在最后一次注射后24小时，处死所有接受治疗的动物以及接受赋形剂治疗的对照组动物。通过测量两种类固醇生成关键酶——δ5-3β羟类固醇脱氢酶（δ5-）和17β羟类固醇脱氢酶（17β-HSD）的活性来评估睾丸类固醇生成活性。通过计算生精周期VII期的生殖细胞数量来确定配子生成能力。采用放射免疫分析法（RIA）测量血浆中促卵泡激素（FSH）、促黄体生成素（LH）、催乳素（PRL）和睾酮（T）的水平。按0.1毫克/100克体重的剂量给予氯化锂21天，导致血浆FSH、LH、PRL和T无显著变化，同时睾丸δ5-3β-HSD、17β-HSD活性及配子生成未改变。相比之下，0.2毫克锂治疗21天导致血浆FSH（P<0.01）、LH（P<0.001）、PRL（P<0.001）和T（P<0.001）显著降低，同时睾丸δ5-3β-HSD活性（P<0.01）和17β-HSD活性（P<0.001）受到抑制。配子生成活性在细线前期精母细胞（PLSc）和粗线中期精母细胞（mPSC）数量上未表现出任何显著减少，而与对照组相比，在生精周期VII期观察到A型精原细胞（Asg）数量显著减少（P<0.01），以及第7步精子细胞（7Sd）数量显著减少（P<0.001）。锂对睾丸活性的有害作用程度在0.4毫克/100克体重的剂量下变得更加明显。我们的实验结果表明，锂的给药可能与对睾丸活性的显著不良影响有关。此外，由于当血浆锂浓度低于或在治疗范围内时，激素变化和改变的配子生成活性就很明显，我们的数据可能具有一些潜在的临床意义。
