Imaoka S, Yamazoe Y, Kato R, Funae Y
Laboratory of Chemistry, Osaka City University Medical School, Japan.
Arch Biochem Biophys. 1992 Nov 15;299(1):179-84. doi: 10.1016/0003-9861(92)90260-4.
The hormonal regulation of rat renal cytochrome P450s, P450 4A2 (K-5) and K-2, was investigated. The level of P450 4A2 in male rats was five times that in female rats and accounted for some 90% of total cytochrome P450, measured photometrically. Lauric acid omega- and (omega-1)-hydroxylation activities of renal microsomes of male rats were also higher than those of female rats. The sex differences in lauric acid hydroxylation activity seemed to arise from the differences in P450 4A2 concentrations, according to an immunochemical study. P450 K-2 was a female-dominant form in rat kidneys. The level of P450 K-2 in renal microsomes of male rats was one-tenth that of P450 4A2. Castration of male rats decreased the levels of P450 4A2 and treatment of castrated male rats with testosterone reversed the decrease. The castration of male rats decreased the lauric acid hydroxylation of the renal microsomes to the level of female rats. The administration of testosterone to castrated male rats reversed the decrease. Hypophysectomy of male rats decreased the level of P450 4A2 and the administration of growth hormone reversed the decrease when intermittent injections mimicking the male secretory pattern were given, although continuous administration mimicking the female secretory pattern did not. Castration of male rats did not affect the level of P450 K-2, but testosterone decreased its level. Hypophysectomy of male rats increased the level of P450 K-2 and growth hormone decreased its level in hypophysectomized rats. These results suggested that the expression of P450 4A2 was regulated by androgen or growth hormone and regulation of P450 4A2 was different from that of P450 K-2. To explore the regulation of renal cytochrome P450 further, testosterone was given to control (intact) or hypophysectomized adult female rats. P450 4A2 was induced in the kidneys of both control and hypophysectomized female rats to close to the level of male rats. Thus, P450 4A2 was directly regulated by testosterone as well as growth hormone, and the regulation of the male-dominant form in rat kidneys was different from that of the male-specific form in the rat liver, which is regulated mostly by growth hormone.
研究了大鼠肾细胞色素P450s、P450 4A2（K-5）和K-2的激素调节。雄性大鼠中P450 4A2的水平是雌性大鼠的五倍，通过光度法测定，约占总细胞色素P450的90%。雄性大鼠肾微粒体的月桂酸ω-和（ω-1）-羟基化活性也高于雌性大鼠。根据一项免疫化学研究，月桂酸羟基化活性的性别差异似乎源于P450 4A2浓度的差异。P450 K-2是大鼠肾脏中以雌性为主的形式。雄性大鼠肾微粒体中P450 K-2的水平是P450 4A2的十分之一。雄性大鼠去势后P450 4A2水平降低，用睾酮治疗去势雄性大鼠可逆转这种降低。雄性大鼠去势后，肾微粒体的月桂酸羟基化水平降至雌性大鼠的水平。给去势雄性大鼠注射睾酮可逆转这种降低。雄性大鼠垂体切除后P450 4A2水平降低，当给予模仿雄性分泌模式的间歇性注射时，生长激素的给药可逆转这种降低，而模仿雌性分泌模式的连续给药则不能。雄性大鼠去势不影响P450 K-2的水平，但睾酮会降低其水平。雄性大鼠垂体切除会增加P450 K-2的水平，而生长激素会降低垂体切除大鼠中P450 K-2的水平。这些结果表明，P450 4A2的表达受雄激素或生长激素调节，且P450 4A2的调节与P450 K-2不同。为了进一步探索肾细胞色素P450的调节，给对照（完整）或垂体切除的成年雌性大鼠注射睾酮。对照和垂体切除的雌性大鼠肾脏中的P450 4A2均被诱导至接近雄性大鼠的水平。因此，P450 4A2直接受睾酮以及生长激素的调节，大鼠肾脏中以雄性为主的形式的调节与大鼠肝脏中以雄性特异性为主的形式不同，后者主要受生长激素调节。
