Abstract
In the present study, changes in the mRNAs of two major forms of hydroxysteroid sulfotransferases (STs), ST2A1 and ST2A2, have been determined in different growth hormone (GH) states. Hepatic ST2A1 mRNA was detected in both sexes of mature Sprague-Dawley rats. The level was 5 times higher in the females than in the males. ST2A1 mRNA was undetectable in GH-deficient animals, such as hypophysectomized rats and spontaneous dwarf rats. Continuous infusion of GH (mimicking the female secretory pattern) increased hepatic levels of ST2A1 mRNA in both GH-deficient animals. ST2A2 mRNA was detected only in the livers of mature female rats and in both sexes of GH-deficient animals. Intermittent injection of GH (mimicking male secretory pattern) strongly suppressed hepatic levels of ST2A2 mRNA in both GH-deficient animals. These results indicate that pituitary GH independently regulates both ST2A1 and ST2A2 at the pretranslational levels. These differences in GH responses between ST2A1 and ST2A2 are in good agreement with their female-dominant and female-specific modes of expression in normal rats. Furthermore, the present study demonstrates a unique response of ST2A2 to the secretory pattern of GH among the drug-metabolizing enzymes in rat livers, in which ST2A2 mRNA levels are suppressed by the male secretory pattern but not by the female secretory pattern of GH.
Footnotes
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Send reprint requests to: Miki Shimada, Ph.D., Division of Drug Metabolism and Molecular Toxicology, Faculty of Pharmaceutical Sciences, Tohoku University, Aramaki-Aoba, Aoba-ku, Sendai, 980–77, Japan.
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↵1 This work was supported in part by Grants-in-Aid from the Ministry of Education, Science and Culture and the Ministry of Health and Welfare and by the Foundation for Advancement of International Science and the Japan Health Sciences Foundation.
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↵2 According to the similarity of deduced amino acid sequences of ST cDNAs, hydroxysteroid ST is proposed to constitute a gene family (ST2). Rat ST is termed following a proposed nomenclature (Yamazoe et al., 1994).
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↵3 Ueda, et al., manuscript in preparation.
- Abbreviations:
- GH
- growth hormone
- ST
- sulfotransferase
- DHEA
- dehydroepiandrosterone
- SD
- Sprague-Dawley
- P450
- cytochrome P450
- SDS
- sodium dodecyl sulfate
- Received October 1, 1996.
- Accepted April 15, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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