Regulation of sulfotransferase mRNA expression in male and female rats of various ages
Regulation of sulfotransferase mRNA expression in male and female rats of various ages
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DOI：
10.1016/s0009-2797(97)00141-5
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发表时间：
1998-02-20
影响因子：
5.1
通讯作者：
Dunn, RT
中科院分区：
文献类型：
--
作者：
Klaassen, CD;Liu, L;Dunn, RT
磺基转移酶是一种第二相药物代谢酶，催化内源化合物(包括类固醇和神经递质)和某些外源化合物(包括N-羟基-2-乙酰氨基氟和酚类化合物，如α-萘酚)加成硫基。与某些I期药物代谢酶相比，人们对磺基转移酶的调节知之甚少。这一系列研究旨在分析雄性和雌性大鼠sult mRNA的表达和激素调节。检测了六种不同亚型的肝脏表达，其中包括三种苯酚硫化物和三种羟基类固醇硫化物。在成年大鼠和发育中的大鼠中，以及在去垂体(HX)和添加生长激素的HX动物中检测SULT mRNA的表达。SULT1A1被认为对简单酚的硫酸盐化很重要，它在成年雄性大鼠中的mRNA表达大约是雌性大鼠的两倍。这种SULT1A1 mRNA水平的差异很大程度上是由于雌性大鼠在青春期后mRNA水平的下降幅度大于雄性大鼠。切除垂体后，雄性和雌性大鼠SULT1A1基因的表达均下降。间歇注射生长激素(雄模式)或输注生长激素(雌模式)均不能恢复SULT1A1的表达。磺基转移酶SULT1C1与N-羟基乙酰氨基氟的激活有关。与SULT1A1相反，SULT1C1mRNA在成年雄性大鼠中的表达大约是成年雌性大鼠的10倍。这种雄性显性表达模式出现在40-50日龄，是由于雄性SULT1C1mRNA的增加。切除垂体后，雄性大鼠SULT1c1表达减弱。有趣的是，注射生长激素(雄性模式)恢复了雄性SULT1C1mRNA的表达，并使雌性大鼠的SULT1C1mRNA表达增强到成年雄性大鼠的水平。GH注射(雌性模式)对雄性和雌性大鼠的SULT1C1mRNA表达都没有影响。雌激素硫转移酶(SULT1E2)可能在雌激素动态平衡中起作用。成年雄性大鼠SULT1E2mRNA的表达水平比成年雌性大鼠高10倍，与SULT1C1相似，这是由于雄性大鼠青春期SULT1E2mRNA表达增加所致。去垂体对雄性大鼠SULT1E2的表达无明显影响，但与雄性大鼠相比，雌性大鼠的SULT1E2表达显著增加。GH输注可抑制HX雄性大鼠SULT1E_2水平。同时检测羟化类固醇磺基转移酶的表达。SULT-20/21亚型在雄性和雌性大鼠中均有表达。雄性在30日龄时表达达到高峰，然后下降到成年雌性的30%左右。SULT-20/21mRNA的表达在45d龄雌性大鼠显著增加，并持续升高。去甲状旁腺后，雌雄大鼠脑组织中sULT-20/21mRNA的表达均明显降低。GH注射不影响HX雄性SULT-20/21mRNA的表达，但使HX雌性SULT-20/21mRNA的表达增加4倍。GR输注可恢复HX雄性大鼠SULT-20/21的表达。GK输注可增加雌性HX大鼠sULT-20/21mRNA的表达，但不能达到正常雌性大鼠的水平。羟基类固醇sult-40/41在成年雌性大鼠中有表达，但在成年雄性大鼠中不表达，雄性和雌性大鼠在15日龄时表达最高，此后逐渐下降。这种表达的减少在雄性大鼠中更为明显。SULT-60mRNA和SULT-40/41一样，仅在成年雌性大鼠中表达。雄性大鼠在30日龄时表达sULT-60，但在60日龄时检测不到sULT-60mRNA。雌性SULT-60mRNA仅在30d后表达，此后雌性SULT-60mRNA仍有较高表达。HX可上调雄性大鼠SULT-40/41和SULT-60mRNA的表达，降低雌性大鼠SULT-40/41和SULT-60mRNA的表达。GH注射抑制雄性SULT-40/41和SULT-60的表达，但不改变雌性SULT-40/41和SULT-60的表达。GH输注不改变雄性SULT-40/41或SULT-60的表达，但略微增加雌性SULT-40/41或SULT-60的表达。总而言之，苯酚转移酶SULT1A1的表达以雄性为主(是雄性的2倍)，而SULT1C1和SULT1E2是雄性特有的，因为它们在成年雄性大鼠中的表达水平是雌性大鼠的10倍。SULT1A1的表达似乎不受GH的调节。在雄性中，SULT1C1的表达受雄性GH分泌模式的控制，而在雌性中，SULT1E2的表达受雌性GH分泌模式的抑制。羟基类固醇硫化物主要在成年雌性大鼠中表达，但在未成熟雄性大鼠中也有瞬时表达。SULT-20/21以雌性为主，在成年雄性大鼠中的表达水平是雌性的30%，而SULT-40/41和SULT-60是雌性特有的，因为它们在成年雄性大鼠中检测不到。GH输注可增强HX大鼠的SULT-20/21，但对SULT-40/41和SULT-60的影响较小。(C)1998爱思唯尔爱尔兰科学有限公司。保留所有权利。
Sulfotransferases (SULTs) are Phase II drug-metabolizing enzymes that catalyze the addition of a sulfuryl moiety to both endogenous compounds, including steroids and neurotransmitters, and certain xenobiotics, including N-hydroxy-2-acetylaminofluorine and phenolic compounds, like a-naphthol. In contrast to certain Phase I drug-metabolizing enzymes, little is known about the regulation of the sulfotransferases. These series of studies were designed to analyze SULT mRNA expression and hormonal regulation in male and female rats. The hepatic expression of six different SULT isoforms was examined including three phenol SULTs and three hydroxysteroid SULTs. SULT mRNA expression was examined in adult and developing rats, as well as, in hypophysectomized (HX) and growth hormone-supplemented HX animals. SULT1A1 is thought to be important for the sulfation of simple phenols and its mRNA expression is about twice as high in adult male as in female rats. This difference in SULT1A1 mRNA levels is largely due to a greater decrease in mRNA levels after puberty in female than in male rats. Hypophysectomy resulted in a decrease in expression of SULT1A1 mRNA in both male and female rats. Replacement of growth hormone (GH) by either intermittent injection (male pattern) or infusion (female pattern) failed to restore SULT1A1 expression. Sulfotransferase SULT1C1 has been implicated in activation of N-hydroxyacetylaminofluorine. In contrast to SULT1A1, SULT1C1 mRNA expression is about 10-fold higher in adult males than in adult female rats. This male-dominant expression pattern emerges at 40-50 days of age and is due to an increase in SULT1C1 mRNA in males. Hypophysectomy abolished SULT1C1 expression in male rats. Interestingly, replacement of GH by injection (male pattern) restored SULT1C1 mRNA expression in males and enhanced SULT1C1 expression in female rats to levels observed in adult male rats.GH infusion (female pattern) did not affect SULT1C1 mRNA expression in either male or female rats. Estrogen sulfotransferase (SULT1E2) may play a role in estrogen homeostasis. Adult male rats express SULT1E2 mRNA al levels 10-fold higher than those observed in adult females and similar to SULT1C1, this is due to an increase in SULT1E2, mRNA occurring during puberty in the male rat. Hypophysectomy did not appreciably affect SULT1E2 expression in male rats; however in contrast to males, hypophysectomy markedly enhanced SULT1E2 expression in female rats. GH infusion suppressed SULT1E2 levels in HX male rats. The expression of hydroxysteroid sulfotransferases was also examined. The SULT-20/21 isoform was expressed in both male and female rats. Male expression of this isoform peaked at 30 days of age and then declined to similar to 30% of the level observed in adult females. SULT-20/21 mRNA expression increased sharply at 45 days of age in female rats and remained elevated. Expression of SULT-20/21 mRNA was decreased markedly by hypophysectomy in both male and female rats. GH injection did not affect SULT-20/21 mRNA expression in HX males, however this treatment resulted in a 4-fold increase in SULT-20/21 mRNA in HX females. GR infusion restored SULT-20/21 expression in HX-male rats. GK infusion did elevate SULT-20/21 mRNA expression in female-HX rats, but not to the level observed in intact females. Hydroxysteroid SULT isoform SULT-40/41 was expressed in adult female but not adult male rats, SULT-40/41 expression peaked at 15 days of age in both male and female rats and decreased thereafter. The decrease in expression was more pronounced in male rats. SULT-60 mRNA, like SULT-40/41, was expressed only in adult female rats. Male rats express SULT-60 at 30 days of age, but SULT-60 mRNA is undetectable at 60 days. SULT-60 mRNA was expressed in females only after day 30 and female SULT-60 mRNA expression remains high thereafter. SULT-40/41 and SULT-60 mRNA expression was increased by HX in male rats and decreased by HX in female rats. GH injection suppressed the expression of SULT-40/41 and SULT-60 in males, but did not alter their expression in females. GH infusion did not alter SULT-40/41 or SULT-60 expression in males, but slightly increased the expression of these isoforms in females. In summary, expression of phenol sulfotransferase SULT1A1 was found to be male predominant (2-fold greater) In contrast to isoforms SULT1C1 and SULT1E2, which were male-specific in that they were expressed at 10-fold higher levels in adult male than in female rats. SULT1A1 expression did not appear to be regulated by GH. SULT1C1 expression in males was controlled by the male GH secretory pattern, while in females SULT1E2, expression was suppressed by the female GH secretory pattern. The hydroxysteroid SULTs were primarily expressed in adult female rats, although transient expression in immature male rats was detected. SULT-20/21 was female predominant as it was expressed in adult male rats at 30% of the female level, whereas SULT-40/41 and SULT-60 were female specific as they were undetectable In adult male rats. GH infusion (female pattern) enhanced SULT-20/21 in HX rats, but had less of an effect on SULT-40/41 and SULT-60. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.