Hassan A S, Hackley J J, Fischer C J
Biochem Med Metab Biol. 1986 Aug;36(1):75-81. doi: 10.1016/0885-4505(86)90109-x.
The objective of this study was to examine the effect of glucocorticoid treatment in early neonatal life on plasma cholesterol and hepatic cholesterol 7 alpha-hydroxylase (CH-7A), the rate-limiting enzyme of bile acid biosynthesis from cholesterol, measured at weaning (Postnatal Day 20). Neonatal rat pups were injected subcutaneously with 5 micrograms of dexamethasone (DEXA) or vehicle (CON) for 5 days between Postnatal Days 4 and 8. On Postnatal Day 20, the animals were used for various studies. DEXA-treated pups weighed significantly less (P less than 0.001) than controls. Even though DEXA-treated animals had significantly smaller livers (P less than 0.001), microsomal protein per gram of liver was significantly greater (P less than 0.005) in the DEXA-treated animals. CH-7A activity (pmole/mg . min) was significantly lower (P less than 0.005) in the DEXA-treated animals (CON (4) 19.4 +/- 2.8; DEXA (4) 5.0 +/- 1.0). Plasma cholesterol (mg/100 ml) was significantly greater (P less than 0.005) in the DEXA-treated animals (CON (5) 179 +/- 7; DEXA (4) 223 +/- 5), a finding consistent with lower CH-7A activity in this group. Taurocholate absorption by in situ ileal loops in anesthetized rats was significantly greater in the DEXA-treated animals in agreement with the in vitro observations of Little and Lester. The basis for the reduced CH-7A activity in DEXA-treated pups is not known. It may be due in part to a new steady state in the enterohepatic circulation of bile acids resulting from a glucocorticoid-induced enhanced conservation of bile acids.
本研究的目的是检测新生早期糖皮质激素治疗对断奶时（出生后第20天）血浆胆固醇和肝脏胆固醇7α-羟化酶（CH-7A）的影响，CH-7A是胆固醇胆汁酸生物合成的限速酶。出生后第4天至第8天，新生大鼠幼崽皮下注射5微克地塞米松（DEXA）或赋形剂（CON），持续5天。在出生后第20天，将动物用于各项研究。DEXA处理的幼崽体重显著低于对照组（P<0.001）。尽管DEXA处理的动物肝脏明显较小（P<0.001），但每克肝脏的微粒体蛋白在DEXA处理的动物中显著更高（P<0.005）。DEXA处理的动物中CH-7A活性（pmole/mg·min）显著降低（P<0.005）（CON组（4只）19.4±2.8；DEXA组（4只）5.0±1.0）。DEXA处理的动物血浆胆固醇（mg/100 ml）显著更高（P<0.005）（CON组（5只）179±7；DEXA组（4只）223±5），这一发现与该组中较低的CH-7A活性一致。与Little和Lester的体外观察结果一致，DEXA处理的麻醉大鼠原位回肠袢对牛磺胆酸盐的吸收显著更高。DEXA处理的幼崽中CH-7A活性降低的原因尚不清楚。这可能部分归因于糖皮质激素诱导的胆汁酸保存增强导致胆汁酸肠肝循环出现新的稳态。
