Growth hormone-dependent and -independent regulation of cytochrome P-450 isozyme expression in streptozotocin-diabetic rats
| Autor: | Edward T. Morgan, Brian S. Donahue, Anna Skottner-Lundin |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty medicine.medical_treatment Biology Isozyme Glucagon Diabetes Mellitus Experimental Endocrinology Cytochrome P-450 Enzyme System Internal medicine Gene expression Alpha-Globulins medicine Animals Insulin Insulin-Like Growth Factor I Hypophysectomy Cytochrome P450 Rats Inbred Strains Streptozotocin Lipids Growth hormone secretion Rats Isoenzymes Gene Expression Regulation Liver Growth Hormone biology.protein Microsomes Liver Female Apoproteins Hormone medicine.drug |
| Zdroj: | Europe PubMed Central Scopus-Elsevier |
| ISSN: | 0013-7227 |
| Popis: | The sexually dimorphic GH secretory pattern is thought to be the major factor regulating constitutive expression of hepatic P450IIC11 (P-450h) and P450IIC12 (P-450i). In this study we investigated whether factors other than the diabetes-induced decrease in GH secretion contribute to alterations in P-450 isozyme expression in streptozotocin (STZ)-diabetic rats. In male rats, hepatic P-450h apoprotein and mRNA decreased to 13% and 24% of control male levels, respectively, within 14 days of STZ injection. STZ-diabetes had little effect on expression of P-450i in females. Treatment of diabetic male rats with GH did not reverse the suppression of P-450h. STZ treatment also suppressed P-450h expression in GH-treated hypophysectomized (Hx) male rats, but incompletely. Thus, GH can partially reverse diabetic suppression of P-450h. However, in Hx male rats without GH supplementation, STZ treatment suppressed P-450h apoprotein and mRNA expression to 16% and 6% of nondiabetic Hx male levels, respectively, demonstrating the existence of GH-independent regulation of P-450h expression. In Hx female rats, P-450h apoprotein levels were 40% of those in intact control males and were not significantly decreased by STZ. Concomitantly, STZ produced a greater decrease in serum insulin levels and a greater increase in serum glucagon in Hx male rats than in Hx females. The results provide evidence for the existence of STZ-sensitive GH-independent expression of P-450h and further document the gender differences in STZ sensitivity. |
| Databáze: | OpenAIRE |
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