Interpulse interval in circulating growth hormone patterns regulates sexually dimorphic expression of hepatic cytochrome P450.
Interpulse interval in circulating growth hormone patterns regulates sexually dimorphic expression of hepatic cytochrome P450.
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循环生长激素模式中的脉冲间隔调节肝细胞色素 P450 的性二态性表达。
DOI：
10.1073/pnas.88.15.6868
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发表时间：
1991
影响因子：
11.1
通讯作者：
Shapiro,BH
中科院分区：
文献类型：
--
作者：
Waxman,DJ;Pampori,NA;Ram,PA;Agrawal,AK;Shapiro,BH
血浆生长激素（GH）的配置文件在许多物种的性分化和调节青春期生长速度和肝功能，包括类固醇羟化酶细胞色素P450表达的性别依赖性，机制知之甚少。通过使用外部泵向切除垂体的大鼠递送不同频率和振幅的大鼠GH脉冲，确定了雄性和雌性GH模式之间肝脏区分的关键要素。肝脏表达的雄性特异性类固醇2 α（或16 α）-羟化酶P450，命名为CYP 2C 11，刺激GH在生理和非生理脉冲幅度，持续时间和频率，提供了一个脉冲间隔没有检测到GH维持至少2.5 hr. This发现表明，肝细胞经历一个强制性的恢复期后，刺激GH脉冲。这段时间可能需要重置GH激活的细胞内信号传导途径，或可能与GH结合和受体内化周期后肝细胞表面GH受体的短期缺乏有关。这些要求被区分从那些必要的刺激GH的垂体切除大鼠的正常男性的生长速度，表明不同的GH反应，也许，不同的GH反应组织识别不同的信号元件在循环GH的性二态模式。
Plasma growth hormone (GH) profiles are sexually differentiated in many species and regulate the sex-dependence of peripubescent growth rates and liver function, including steroid hydroxylase cytochrome P450 expression, by mechanisms that are poorly understood. By use of an external pump to deliver to hypophysectomized rats pulses of rat GH of varying frequency and amplitude, a critical element for liver discrimination between male and female GH patterns was identified. Liver expression of the male-specific steroid 2 alpha (or 16 alpha)-hydroxylase P450, designated CYP2C11, was stimulated by GH at both physiological and nonphysiological pulse amplitudes, durations, and frequencies, provided that an interpulse interval of no detectable GH was maintained for at least 2.5 hr. This finding suggests that hepatocytes undergo an obligatory recovery period after stimulation by a GH pulse. This period may be required to reset a GH-activated intracellular signaling pathway or may relate to the short-term absence of GH receptors at the hepatocyte surface after a cycle of GH binding and receptor internalization. These requirements were distinguished from those necessary for the stimulation by GH of normal male growth rates in hypophysectomized rats, indicating that different GH responses and, perhaps, different GH-responsive tissues recognize distinct signaling elements in the sexually dimorphic patterns of circulating GH.