Srivastava P K, Waxman D J
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.
Biochem J. 1993 Aug 15;294 ( Pt 1)(Pt 1):159-65. doi: 10.1042/bj2940159.
The sex-dependent expression and growth hormone (GH) regulation of rat liver glutathione S-transferase (GST) was examined using oligonucleotide probes that distinguish between closely related class Alpha (Ya1, Ya2, Yc) and class Mu (Yb1, Yb2, Yb3) GST mRNAs [Waxman, Sundseth, Srivastava and Lapenson (1992) Cancer Res. 52, 5797-5802]. Northern-blot analysis revealed that the steady-state levels of GST Ya1, Yb1 and Yb2 mRNAs are 2.5-3-fold higher in male as compared with female rat liver. In contrast, GST Yc and Ya2 mRNAs were expressed at a 2-3-fold higher level in female rat liver. Microsomal GST mRNA did not exhibit significant sex-dependent differences in rat liver. Treatment of male rats with GH by continuous infusion suppressed expression of the male-dominant GST Ya1, Yb1 and Yb2 mRNAs to levels at or below those found in female rat liver. This suppressive effect of GH was liver-specific, insofar as GH treatment did not alter kidney GST Ya1 mRNA levels. Hypophysectomy increased expression of the male-dominant GSTs, particularly in female rats (e.g. 8-fold elevation of GST Ya1 mRNA). GST Yc mRNA was increased approx. 2-fold in hypophysectomized males, indicating that this mRNA is subject to negative regulation by one or more pituitary-dependent factors. Continuous GH treatment of the hypophysectomized rats suppressed the expression of mRNA of GSTs Ya1, Yb1 and Yb2 when given as a continuous infusion, but not when given by an intermittent (twice daily) GH-injection schedule. Combination of continuous exposure to GH with thyroxine treatment resulted in a more complete suppression of GSTs Ya1, Yb1 and Yb2. In contrast, thyroxine increased the expression of GST Yc in hypophysectomized rats. These studies establish that several Alpha and Mu class GSTs are expressed in a sex-dependent fashion in adult rat liver, where they are regulated by multiple pituitary-dependent hormones through pretranslational mechanisms.
利用能区分密切相关的α类（Ya1、Ya2、Yc）和μ类（Yb1、Yb2、Yb3）谷胱甘肽S-转移酶（GST）mRNA的寡核苷酸探针，研究了大鼠肝脏GST的性别依赖性表达及生长激素（GH）调节作用[Waxman、Sundseth、Srivastava和Lapenson（1992年）《癌症研究》52，5797 - 5802]。Northern印迹分析显示，与雌性大鼠肝脏相比，雄性大鼠肝脏中GST Ya1、Yb1和Yb2 mRNA的稳态水平高2.5 - 3倍。相反，GST Yc和Ya2 mRNA在雌性大鼠肝脏中的表达水平高2 - 3倍。微粒体GST mRNA在大鼠肝脏中未表现出明显的性别依赖性差异。通过持续输注用GH处理雄性大鼠，可将雄性优势的GST Ya1、Yb1和Yb2 mRNA的表达抑制至雌性大鼠肝脏中发现的水平或以下。GH的这种抑制作用具有肝脏特异性，因为GH处理并未改变肾脏GST Ya1 mRNA水平。垂体切除增加了雄性优势GST的表达，特别是在雌性大鼠中（例如，GST Ya1 mRNA升高8倍）。GST Yc mRNA在垂体切除的雄性大鼠中增加约2倍，表明该mRNA受一种或多种垂体依赖性因子的负调节。对垂体切除的大鼠持续给予GH处理，如果是持续输注给药，则可抑制GST Ya1、Yb1和Yb2 mRNA的表达，但如果是间歇性（每日两次）GH注射给药则不能。持续暴露于GH与甲状腺素处理相结合，可更完全地抑制GST Ya1、Yb1和Yb2。相反，甲状腺素增加了垂体切除大鼠中GST Yc的表达。这些研究表明，几种α类和μ类GST在成年大鼠肝脏中以性别依赖性方式表达，在那里它们通过翻译前机制受多种垂体依赖性激素调节。
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