Liu A, Flores C, Kinkead T, Carboni A A, Menon M, Seethalakshmi L
Division of Urologic and Transplantation Surgery, University of Massachusetts Medical Center, Worcester 01655.
J Urol. 1994 Aug;152(2 Pt 1):554-61. doi: 10.1016/s0022-5347(17)32792-1.
The effect of sialoadenectomy (Sx) and epidermal growth factor (EGF) administration on testicular function was investigated in 8-week old C3H mice. Animals were divided initially into three groups: sham operated controls, Sx, and Sx + EGF treated (100 micrograms./kg./day subcutaneously for 28 days). Sialoadenectomy completely depleted the circulating levels of EGF and reduced body weight and reproductive organ weights. However, kidney weight was not affected. Quantitative analysis of spermatogenesis showed a decrease in preleptotene and pachytene spermatocytes and round spermatids, which resulted in a decrease in sperm counts. Sperm motility and fertility were also significantly decreased. Endocrinologic studies showed a 2- and 6-fold elevation in intratesticular and serum levels of testosterone and a decrease in luteinizing hormone (LH) levels. Follicle stimulating hormone levels were not altered. Administration of EGF to the Sx animals maintained reproductive organ weights, spermatogenesis and levels of LH and testosterone closer to control values; however, sperm motility was not maintained at control value. That sialoadenectomy resulted in a decline in androgen-dependent parameters, in spite of an elevation in testosterone levels, and EGF maintained them closer to the control value suggested that EGF may modulate androgen action. A comparison was therefore carried out between the effects of Sx and administration of flutamide (F), an androgen receptor blocker. Animals were subjected to Sx, F treatment (100 mg./kg./day subcutaneously for 28 days), Sx + F, or Sx + F + EGF. The effects of Sx and F treatment on organ weights, sperm counts and sperm motility were more or less similar. As expected, flutamide treatment increased LH and FSH levels, and testosterone levels were normal. The Sx + F animals showed no further decrease in organ weights, sperm count and motility. Treatment with Sx + F increased intratesticular and serum levels of testosterone by 2- and 10-fold. Circulating levels of LH and FSH were the same as in the flutamide-treated group. Administration of EGF to Sx + F maintained all these parameters, except sperm motility, closer to the control value. These results suggest that EGF either bypasses flutamide effects and acts directly or that EGF modulates androgen action at one or more steps in the signal transduction pathway in the male reproductive organs.
研究了涎腺切除术（Sx）和给予表皮生长因子（EGF）对8周龄C3H小鼠睾丸功能的影响。动物最初被分为三组：假手术对照组、接受涎腺切除术的组以及接受涎腺切除术并给予EGF治疗的组（皮下注射100微克/千克/天，持续28天）。涎腺切除术使循环中的EGF水平完全降低，并使体重和生殖器官重量减轻。然而，肾脏重量未受影响。精子发生的定量分析显示，细线前期和粗线期精母细胞以及圆形精子细胞数量减少，导致精子计数下降。精子活力和生育能力也显著降低。内分泌学研究表明，睾丸内和血清中的睾酮水平分别升高了2倍和6倍，而黄体生成素（LH）水平降低。促卵泡激素水平未改变。给接受涎腺切除术的动物注射EGF可使生殖器官重量、精子发生以及LH和睾酮水平更接近对照值；然而，精子活力未能维持在对照值水平。尽管睾酮水平升高，但涎腺切除术导致雄激素依赖参数下降，而EGF使其更接近对照值，这表明EGF可能调节雄激素作用。因此，对涎腺切除术的影响与给予雄激素受体阻滞剂氟他胺（F）的影响进行了比较。动物接受涎腺切除术、氟他胺治疗（皮下注射100毫克/千克/天，持续28天）、涎腺切除术 + 氟他胺治疗或涎腺切除术 +氟他胺 + EGF治疗。涎腺切除术和氟他胺治疗对器官重量、精子计数和精子活力的影响大致相似。正如预期的那样，氟他胺治疗使LH和FSH水平升高，而睾酮水平正常。接受涎腺切除术 + 氟他胺治疗的动物在器官重量、精子计数和活力方面没有进一步下降。涎腺切除术 + 氟他胺治疗使睾丸内和血清中的睾酮水平分别升高了2倍和10倍。循环中的LH和FSH水平与氟他胺治疗组相同。给接受涎腺切除术 + 氟他胺治疗的动物注射EGF可使除精子活力外的所有这些参数更接近对照值。这些结果表明，EGF要么绕过氟他胺的作用直接发挥作用，要么在雄性生殖器官信号转导途径的一个或多个步骤中调节雄激素作用。
