Esquifino A I, Moreno M L, Agrasal C, Villanúa M A
Departamento de Bioquímica, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
Proc Soc Exp Biol Med. 1995 Apr;208(4):397-403. doi: 10.3181/00379727-208-43868.
Effects of cyclosporine (CyA) on ovarian function and the possible role of prolactin in mediating these effects were examined in young female rats. The animals were sham-operated or rendered hyperprolactinemic by transplanting pituitary glands under the renal capsule. Cyclosporine prevented the increase in plasma prolactin levels in grafted rats. However, in sham-operated animals plasma prolactin levels were increased after 8 days of CyA treatment. Plasma levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were reduced 8 days after pituitary grafting and increased by CyA at both Day 2 and Day 8 of treatment. The content of LHRH in the hypothalamus was not affected on Day 2 but was reduced on Day 8 after grafting on CyA therapy. Plasma estradiol levels were increased by CyA in sham-operated rats on Day 2 and 8 of treatment, and in pituitary-grafted rats on Day 8 of therapy. In sham-operated rats, ovarian estradiol content was reduced after 2 and after 8 days of CyA administration. In pituitary-grafted rats, the ovarian estradiol content was suppressed after 8 days, and CyA treatment prevented this effect. Ovarian estradiol release in vitro under basal conditions was greater in ovaries derived from 38-day-old than in those from 32-day-old animals. The ovarian estradiol response to human chorionic gonadotropin (hCG) in vitro was increased 2 days after pituitary transplantation. Administration of CyA for 8 days increased basal and hCG-stimulated estradiol release in both sham-operated and pituitary-grafted animals. The present findings suggest that CyA can alter ovarian function by acting directly at the gonadal level. However, a hypothalamic-hypophyseal site of action cannot be ruled out.
在年轻雌性大鼠中研究了环孢素（CyA）对卵巢功能的影响以及催乳素在介导这些影响中可能发挥的作用。对动物进行假手术，或通过将垂体移植到肾包膜下使其产生高催乳素血症。环孢素可阻止移植大鼠血浆催乳素水平的升高。然而，在假手术动物中，环孢素治疗8天后血浆催乳素水平升高。垂体移植8天后，黄体生成素（LH）和促卵泡激素（FSH）的血浆水平降低，而在治疗第2天和第8天时，环孢素使其升高。下丘脑促性腺激素释放激素（LHRH）的含量在治疗第2天时未受影响，但在移植环孢素治疗8天后降低。在假手术大鼠中，治疗第2天和第8天时，环孢素使血浆雌二醇水平升高；在垂体移植大鼠中，治疗第8天时，环孢素使其升高。在假手术大鼠中，环孢素给药2天和8天后，卵巢雌二醇含量降低。在垂体移植大鼠中，8天后卵巢雌二醇含量受到抑制，而环孢素治疗可防止这种作用。在基础条件下，38日龄动物卵巢的体外雌二醇释放量高于32日龄动物。垂体移植2天后，卵巢对人绒毛膜促性腺激素（hCG）的体外雌二醇反应增强。环孢素给药8天可增加假手术和垂体移植动物的基础和hCG刺激的雌二醇释放。目前的研究结果表明，环孢素可通过直接作用于性腺水平来改变卵巢功能。然而，不能排除下丘脑 - 垂体的作用位点。
