Wexler B C, Greenberg B P
Circ Res. 1978 Jan;42(1):126-35. doi: 10.1161/01.res.42.1.126.
Sexually mature, male and female Sprague-Dawley rats were housed in large communal breeding cages or in smaller paired breeding cages. Virgin control rats of the same age were housed similarly but segregated by sex. Breeders became obese, developed a fatty liver, and showed elevated levels of triglycerides, free fatty acids, and cholesterol. Breeders had high blood pressure, enlarged hearts, hyperglycemia, and islet beta cell degranulation. Serum enzymes, creatine phosphokinase, serum glutamic oxalo-pyruvic transaminase, serum glutamic pyruvic transaminase, lactate dehydrogenase, and blood urea nitrogen levels were elevated in breeder rats. The adrenal glands of male breeders appeared hyperactive; the adrenal glands of female breeders were thrombosed and appeared to be hypoactive. Male breeder rats developed microscopic aortic lesions only; female breeders developed advanced calcific aortic sclerosis. Male breeders kept in active stud service manifested the most abnormal metabolic and pathophysiological changes. Female breeders developed similar pathophysiological changes after four pregnancies, irrespective of their paired or communal breeding environment. Virgin rats were normal regardless of housing conditions. Our findings suggest that repeated breeding in male and female rats causes resetting of the hypothalamic-pituitary-adrenal-gonadal axis. This may lead to disturbed hormonal and metabolic changes which culminate with the development of accelerated cardiovascular degenerative changes.
性成熟的雄性和雌性斯普拉格-道利大鼠被饲养在大型公共繁殖笼或较小的成对繁殖笼中。相同年龄的未交配对照大鼠以类似方式饲养，但按性别分开。繁殖大鼠变得肥胖，出现脂肪肝，并表现出血清甘油三酯、游离脂肪酸和胆固醇水平升高。繁殖大鼠患有高血压、心脏增大、高血糖和胰岛β细胞脱颗粒。繁殖大鼠的血清酶、肌酸磷酸激酶、血清谷草转氨酶、血清谷丙转氨酶、乳酸脱氢酶和血尿素氮水平升高。雄性繁殖大鼠的肾上腺似乎功能亢进；雌性繁殖大鼠的肾上腺出现血栓形成，似乎功能减退。雄性繁殖大鼠仅出现微观主动脉病变；雌性繁殖大鼠出现晚期钙化性主动脉硬化。持续进行配种的雄性繁殖大鼠表现出最异常的代谢和病理生理变化。雌性繁殖大鼠在经历四次妊娠后出现类似的病理生理变化，无论其成对或公共繁殖环境如何。未交配大鼠无论饲养条件如何均正常。我们的研究结果表明，雌雄大鼠反复繁殖会导致下丘脑-垂体-肾上腺-性腺轴的重置。这可能导致激素和代谢变化紊乱，最终发展为加速的心血管退行性变化。
