Valdes C T, Elkind-Hirsch K E, Rogers D G, Adelman J P
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas 77030.
Endocrinology. 1991 Jan;128(1):433-40. doi: 10.1210/endo-128-1-433.
Studies in diabetic rats have found abnormalities at the hypothalamic, pituitary, and/or ovarian level but have not controlled for changes in estrogen levels induced by diabetes. The purpose of this investigation was to study the effect of diabetes on the hypothalamic-pituitary axis in ovariectomized rats treated with estradiol (E2). Ovariectomized 60 day old female rats were assigned to control (C, n = 42), diabetic (D, n = 47) or insulin-treated diabetic (DI, n = 16) groups. Diabetes was induced with an injection of streptozotocin in the D and DI groups. In the C, D, and DI groups, estrogen was replaced by implanting blank, 5 micrograms or 20 micrograms E2 pellets sc. Pituitary LH responsiveness to GnRH was assessed in C and D animals. Anterior hypothalamic and midhypothalamic concentrations of proGnRH and GnRH, pituitary LH and FSH and serum levels of LH, and E2 were measured by RIA. Anterior hypothalamic proGnRH concentrations were decreased in diabetic rats treated with 5 micrograms E2 compared to 5 micrograms E2 control animals (P less than 0.05). Midhypothalamic GnRH concentrations were also reduced in D vs. C animals despite comparable estrogen therapy (P less than 0.004). GnRH-stimulated LH levels were greater in E2-treated diabetic females than in similarly treated control rats (P less than 0.001). D and DI animals were more sensitive than controls to the inhibitory effect of estrogen on basal LH levels. Pituitary LH and FSH content was lower in 20 micrograms E2-replaced animals but was not influenced by the diabetic state. These data demonstrate a diabetes-induced decrease in hypothalamic proGnRH and GnRH concentration which is not corrected with E2 replacement. The hyper-responsiveness of the diabetic rat pituitary to GnRH also suggests a chronic lack of GnRH stimulation from the hypothalamus but a continued ability of the pituitary to respond to GnRH.
对糖尿病大鼠的研究发现，下丘脑、垂体和/或卵巢水平存在异常，但未对糖尿病引起的雌激素水平变化进行控制。本研究的目的是研究糖尿病对用雌二醇（E2）治疗的去卵巢大鼠下丘脑-垂体轴的影响。将60日龄去卵巢雌性大鼠分为对照组（C，n = 42）、糖尿病组（D，n = 47）或胰岛素治疗糖尿病组（DI，n = 16）。D组和DI组通过注射链脲佐菌素诱导糖尿病。在C组、D组和DI组中，通过皮下植入空白、5微克或20微克E2丸剂来替代雌激素。评估C组和D组动物垂体促黄体生成素（LH）对促性腺激素释放激素（GnRH）的反应性。通过放射免疫分析（RIA）测量下丘脑前部和下丘脑中部促GnRH和GnRH的浓度、垂体LH和促卵泡生成素（FSH）以及血清LH和E2水平。与接受5微克E2治疗的对照动物相比，接受5微克E2治疗的糖尿病大鼠下丘脑前部促GnRH浓度降低（P < 0.05）。尽管雌激素治疗相当，但D组动物下丘脑中部GnRH浓度也低于C组（P < 0.004）。E2治疗的糖尿病雌性大鼠中GnRH刺激的LH水平高于同样治疗的对照大鼠（P < 0.001）。D组和DI组动物比对照组对雌激素对基础LH水平的抑制作用更敏感。在接受20微克E2替代治疗的动物中，垂体LH和FSH含量较低，但不受糖尿病状态影响。这些数据表明，糖尿病导致下丘脑促GnRH和GnRH浓度降低，E2替代治疗无法纠正这一情况。糖尿病大鼠垂体对GnRH的高反应性也表明下丘脑长期缺乏GnRH刺激，但垂体仍有能力对GnRH作出反应。
