Cowley B D, Rupp J C, Muessel M J, Gattone V H
Department of Medicine, University of Kansas Medical Center, Kansas City 66160-7400, USA.
Am J Kidney Dis. 1997 Feb;29(2):265-72. doi: 10.1016/s0272-6386(97)90039-1.
Human autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disease and displays a gender dimorphism in renal disease progression. Han:SPRD-Cy rats manifest a form of ADPKD that is similar in many respects to that seen in humans. In Han:SPRD rats, male Cy/+ rats have more prominent renal changes and develop renal failure at an early age, whereas female Cy/+ rats exhibit less severe renal cystic change and have normal renal function until advanced age. To determine whether the male gonadal hormone, testosterone, contributes to this gender dimorphism, males were sham operated or castrated; some castrated rats were repleted with 5alpha-dihydrotestosterone. Female rats were sham operated or ovariectomized before sham operation or testosterone treatment. All treatments started at 4 weeks of age and ended at 10 weeks of age. Renal enlargement, cystic change, and renal function were assessed. In the males, castration reduced renal enlargement and cystic change; testosterone treatment abrogated these effects. Neither of these manipulations affected azotemia in male Cy/+ rats. In the females, testosterone was renotropic for both normal and cystic kidneys. In the Cy/+ females, testosterone treatment caused azotemia and an increase in the severity of the PKD. Ovariectomy blunted the effect of testosterone on cystic kidney enlargement. Testosterone treatment did not completely erase the gender-associated differences in azotemia in the Cy/+ rat. These data confirm the renotropic effects of testosterone and indicate that testosterone influences the progression of renal cystic change in male and female rats with ADPKD.
人类常染色体显性遗传性多囊肾病（ADPKD）是一种常见的遗传性疾病，在肾脏疾病进展过程中表现出性别差异。Han:SPRD-Cy大鼠表现出一种ADPKD形式，在许多方面与人类所见相似。在Han:SPRD大鼠中，雄性Cy/+大鼠有更明显的肾脏变化，并在早年发展为肾衰竭，而雌性Cy/+大鼠表现出较轻的肾囊性变化，直到老年肾功能仍正常。为了确定男性性腺激素睾酮是否导致这种性别差异，对雄性大鼠进行假手术或去势；一些去势大鼠补充5α-双氢睾酮。雌性大鼠在假手术或睾酮治疗前进行假手术或卵巢切除。所有治疗从4周龄开始，至10周龄结束。评估肾脏肿大、囊性变化和肾功能。在雄性大鼠中，去势减少了肾脏肿大和囊性变化；睾酮治疗消除了这些影响。这些操作均未影响雄性Cy/+大鼠的氮质血症。在雌性大鼠中，睾酮对正常和囊性肾脏均有促肾生长作用。在Cy/+雌性大鼠中，睾酮治疗导致氮质血症并增加PKD的严重程度。卵巢切除减弱了睾酮对囊性肾肿大的影响。睾酮治疗并未完全消除Cy/+大鼠氮质血症中与性别相关的差异。这些数据证实了睾酮的促肾生长作用，并表明睾酮影响雄性和雌性ADPKD大鼠肾囊性变化的进展。
