Egfjord M, Olgaard K
Medical Department P, Rigshospitalet, Copenhagen, Denmark.
Endocrinology. 1989 Dec;125(6):3011-21. doi: 10.1210/endo-125-6-3011.
A sex-dependent metabolism of aldosterone has been reported in intact rats. To further characterize the hepatic elimination of aldosterone and its sex dependence, the metabolism of d-[4-14C]aldosterone was studied in isolated perfused liver from male and female Wistar rats, from male rats castrated 3 weeks before experiments, and from younger male rats (same body weight as the female rats). The livers were perfused at a constant flow rate in a recirculating mode with a hemoglobin-free medium containing aldosterone at initially 1 nM. Perfusate aldosterone was measured by a specific RIA. Total 4-14C radio-activity in perfusate and bile was determined. The perfusate [4-14C]aldosterone radiometabolite concentration was calculated. The radiometabolite pattern in additional experiments was studied by HPLC. The male rats exhibited 10% higher systolic blood pressure (P less than 0.05) and 51% higher fasting values of plasma aldosterone (P less than 0.05) compared to those in the female rats. In female rats the hepatic clearance rate of aldosterone per 100 g BW was 72% higher than that in male rats (11.2 +/- 2.7 to 6.5 +/- 1.8 ml/min: P less than 0.01), and that expressed per g liver wet wt was 75% higher (3.5 +/- 1.0 to 2.0 +/- 0.7 ml/min; P less than 0.01). When female rats were compared to younger male rats with the same body weight, 33% higher hepatic aldosterone clearance rates were still found in female rats (21.0 +/- 5.4 to 15.8 +/- 3.2 ml/min; P less than 0.05), and 51% higher values when expressed per g liver wet wt (3.5 +/- 1.0 to 2.3 +/- 0.5 ml/min; P less than 0.01). No difference in the aldosterone clearance rate was observed in castrated male rats compared to that in noncastrated male rats. 4-14C-Labeled radiometabolite levels accumulated similarly in the perfusate of livers of both sexes. Perfusate 4-14C-labeled radiometabolites after 90 min of perfusion were lower in livers of castrated male rats than in noncastrated male rats (P less than 0.001). The final perfusate 14C-labeled radiometabolite concentration correlated inversely with the total 14C in bile (P less than 0.01). All 14C-labeled radiometabolites detected in perfusate and bile after 90 min were more polar than aldosterone. After enzymatic hydrolysis, some of the metabolites from the male livers cochromatographed with tetrahydro- and dihydroaldosterone, while other fractions remained more polar. Only more polar metabolites were detected in the perfusate and bile of female livers.(ABSTRACT TRUNCATED AT 400 WORDS)
在完整的大鼠中已报道了醛固酮的性别依赖性代谢。为了进一步明确醛固酮的肝脏清除及其性别依赖性特征，研究了d-[4-¹⁴C]醛固酮在雄性和雌性Wistar大鼠、实验前3周去势的雄性大鼠以及较年轻雄性大鼠（与雌性大鼠体重相同）的离体灌注肝脏中的代谢情况。肝脏以恒定流速在循环模式下用最初含1 nM醛固酮的无血红蛋白培养基进行灌注。通过特异性放射免疫分析法测定灌注液中的醛固酮。测定灌注液和胆汁中的总4-¹⁴C放射性。计算灌注液中[4-¹⁴C]醛固酮放射性代谢物浓度。在额外实验中通过高效液相色谱法研究放射性代谢物模式。与雌性大鼠相比，雄性大鼠的收缩压高10%（P<0.05），血浆醛固酮空腹值高51%（P<0.05）。在雌性大鼠中，每100 g体重的醛固酮肝脏清除率比雄性大鼠高72%（11.2±2.7至6.5±1.8 ml/min：P<0.01），以每克肝脏湿重表示则高75%（3.5±1.0至2.0±0.7 ml/min；P<0.01）。当将雌性大鼠与体重相同的较年轻雄性大鼠比较时，雌性大鼠的肝脏醛固酮清除率仍高33%（21.0±5.4至15.8±3.2 ml/min；P<0.05），以每克肝脏湿重表示则高51%（3.5±1.0至2.3±0.5 ml/min；P<0.01）。与未去势雄性大鼠相比，去势雄性大鼠的醛固酮清除率未观察到差异。两性肝脏灌注液中4-¹⁴C标记的放射性代谢物水平积累相似。灌注90分钟后，去势雄性大鼠肝脏灌注液中4-¹⁴C标记的放射性代谢物低于未去势雄性大鼠（P<0.001）。最终灌注液中¹⁴C标记放射性代谢物浓度与胆汁中的总¹⁴C呈负相关（P<0.01）。灌注90分钟后在灌注液和胆汁中检测到的所有¹⁴C标记放射性代谢物比醛固酮极性更强。酶水解后，雄性肝脏中的一些代谢物与四氢醛固酮和二氢醛固酮共色谱，而其他部分极性更强。在雌性肝脏的灌注液和胆汁中仅检测到极性更强的代谢物。（摘要截短至400字）
