Vockentanz B M, Virgo B B
Department of Biological Sciences, University of Windsor, Ont., Canada.
Can J Physiol Pharmacol. 1988 Jul;66(7):868-72. doi: 10.1139/y88-141.
The hepatic monooxygenase system was studied in hypophysectomized female rats infused for 5 days with ovine growth hormone (GH). At 7.5 micrograms.h-1 GH decreased the total cytochrome P-450 by 16%; at 10 micrograms.h-1 it reduced both cytochrome P-450 (31%) and the activity of ethylmorphine demethylase (31%). GH did not alter the activities of NADPH cytochrome c reductase or aniline hydroxylase. The lower GH dose decreased the amount of fast- and slow-turnover P-450 by 11 and 38%, respectively, while the higher dose decreased both by 49%. The loss of demethylase activity therefore correlates with the loss of fast-turnover P-450. This component is relatively more abundant in the female (fast: slow turnover of 4.3) than the male (fast:slow turnover of 2.5). GH did not affect the half-lives of the P-450 components, suggesting that it decreases their synthesis. The P-450 concentration in microsomes from GH-treated animals did not increase after incubation with hemin, suggesting that in vivo the hormone does not lower P-450 synthesis via depression of heme. Puromycin mimicked the effect of GH and when given with the hormone their effects on the P-450 levels were multiplicative (p less than 0.05), suggesting different modes of action and that GH does not decrease P-450 by acting at translation.
对切除垂体的雌性大鼠进行了研究，这些大鼠连续5天输注绵羊生长激素（GH）。在7.5微克·小时⁻¹的GH剂量下，细胞色素P - 450总量降低了16%；在10微克·小时⁻¹时，细胞色素P - 450（降低31%）和N - 乙基吗啡脱甲基酶活性（降低31%）均下降。GH未改变NADPH细胞色素c还原酶或苯胺羟化酶的活性。较低剂量的GH使快速周转和慢速周转的P - 450量分别减少了11%和38%，而较高剂量则使两者均减少了49%。因此，脱甲基酶活性的丧失与快速周转P - 450的丧失相关。该组分在雌性大鼠中相对更丰富（快速周转与慢速周转之比为4.3），而在雄性大鼠中为（快速周转与慢速周转之比为2.5）。GH不影响P - 450组分的半衰期，提示它降低了它们的合成。用血红素孵育后，GH处理动物微粒体中的P - 450浓度未增加，提示在体内该激素并非通过抑制血红素而降低P - 450的合成。嘌呤霉素模拟了GH的作用，当与该激素同时给予时，它们对P - 450水平的影响具有相乘性（P<0.05），提示作用方式不同，且GH并非通过作用于翻译过程来降低P - 450。
