Dudek M, Kołodziejski P A, Pruszyńska-Oszmałek E, Ziarniak K, Sliwowska J H
Laboratory of Neurobiology, Institute of Zoology, Poznan University of Life Sciences, Poznan, Poland.
Department of Animal Physiology and Biochemistry, Poznan University of Life Sciences, Poznan, Poland.
J Neuroendocrinol. 2017 Feb;29(2). doi: 10.1111/jne.12453.
Neurones expressing kisspeptin, neurokinin B and dynorphin A, located in the arcuate nucleus of the hypothalamus (ARC), are important regulators of reproduction. Their functions depend on metabolic and hormonal status. We hypothesised that male rats with high-fat diet-induced obesity (DIO) and/or streptozotocin-induced diabetes mellitus type 1 (DM1) and type 2 (DM2) will have alterations in numbers of immunoreactive (-IR) cells: kisspeptin-IR and/or neurokinin B-IR and dynorphin A-IR neurones in the ARC in the sham condition. In addition, orchidectomy alone (ORX) and with testosterone treatment (ORX+T) will unmask possible deficits in the response of these neurones in DIO, and/or DM1 and DM2 rats. Rats were assigned to four groups: a control (C) and one diabetic group (DM1) were fed a regular chow diet, whereas the obese group (DIO) and the other diabetic group (DM2) were fed a high-fat diet. To induce diabetes, streptozotocin was injected. After 6 weeks, each group was divided into three subgroups: ORX, ORX+T and sham. After another 2 weeks, metabolic and hormonal profiles were assessed and immunocytochemistry was performed. We found that: (1) under sham conditions: (i) DM1 and DM2 animals had higher numbers of kisspeptin-IR cells than controls and (ii) DM2 rats had increased numbers of neurokinin B-IR and dynorphin A-IR cells compared to C animals; (2) ORX and ORX+T treatments unmasked deficits of the studied neurones in DM1 and DM2 but not in DIO animals; and (3) DIO, DM1 and DM2 rats had altered metabolic and hormonal profiles, in particular decreased levels of testosterone. We concluded that alterations in numbers of kisspeptin-IR and neurokinin B-IR neurones in the ARC and their response to ORX and ORX+T may account for disruptions of metabolic and reproductive functions in diabetic but not in obese rats.
位于下丘脑弓状核（ARC）的表达 kisspeptin、神经激肽 B 和强啡肽 A 的神经元是生殖的重要调节因子。它们的功能取决于代谢和激素状态。我们假设，高脂饮食诱导肥胖（DIO）和/或链脲佐菌素诱导的 1 型糖尿病（DM1）和 2 型糖尿病（DM2）的雄性大鼠在假手术条件下，ARC 中免疫反应性（-IR）细胞数量会发生改变：即 kisspeptin-IR 和/或神经激肽 B-IR 以及强啡肽 A-IR 神经元数量会改变。此外，单纯去势（ORX）以及去势加睾酮治疗（ORX+T）将揭示 DIO 和/或 DM1 及 DM2 大鼠中这些神经元反应可能存在的缺陷。大鼠被分为四组：对照组（C）和一个糖尿病组（DM1）喂食常规饲料，而肥胖组（DIO）和另一个糖尿病组（DM2）喂食高脂饮食。为诱导糖尿病，注射链脲佐菌素。6 周后，每组再分为三个亚组：ORX、ORX+T 和假手术组。再过 2 周后，评估代谢和激素谱并进行免疫细胞化学检测。我们发现：（1）在假手术条件下：（i）DM1 和 DM2 动物的 kisspeptin-IR 细胞数量高于对照组，（ii）与 C 组动物相比，DM2 大鼠的神经激肽 B-IR 和强啡肽 A-IR 细胞数量增加；（2）ORX 和 ORX+T 治疗揭示了 DM1 和 DM2 但不是 DIO 动物中所研究神经元的缺陷；（3）DIO、DM1 和 DM2 大鼠的代谢和激素谱发生改变，特别是睾酮水平降低。我们得出结论，ARC 中 kisspeptin-IR 和神经激肽 B-IR 神经元数量的改变及其对 ORX 和 ORX+T 的反应可能是糖尿病大鼠而非肥胖大鼠代谢和生殖功能紊乱的原因。
