Hormonal regulation of cholesterol 7 alpha-hydroxylase specific activity, mRNA levels, and transcriptional activity in vivo in the rat

Title

Hormonal regulation of cholesterol 7 alpha-hydroxylase specific activity, mRNA levels, and transcriptional activity in vivo in the rat

Creator

Pandak W M; Heuman D M; Redford K; Stravitz R T; Chiang J Y L; Hylemon P B; Vlahcevic Z R

Publisher

Journal of Lipid Research

Date

1997
1997-12

Description

In primary cultures of rat hepatocytes, transcription of the cholesterol 7 alpha-hydroxylase gene is induced synergistically by glucocorticoid and thyroid hormones. The objective of the present study was to evaluate the role of glucocorticoid and thyroid hormones in the maintenance of cholesterol 7 alpha-hydroxylase gene expression in vivo. Male Sprague-Dawley rats underwent adrenalectomy (A), thyroidectomy (T), adrenalectomy + thyroidectomy (A + T), hypophysectomy (H), or sham surgery (paired controls). Ten days post surgery, livers were harvested and cholesterol 7 alpha-hydroxylase specific activity, steady-state mRNA levels, and transcriptional activity were determined. Serum corticosterone levels were <2% of paired controls in A, A + T and H rats. Free thyroxine index was <32% of paired controls in rats with T and H. When compared to sham-operated controls, A + T and H led to decreases in cholesterol 7 alpha-hydroxylase specific activities of 44 +/- 8% and 57 +/- 3%, respectively (P < 0.03 and < 0.05). Similar changes were observed in cholesterol 7 alpha-hyroxylase steady-state mRNA levels, which decreased by 43 +/- 10% (P < 0.001) and 56 +/- 19% (P < 0.05), respectively. Cholesterol 7 alpha-hydroxylase transcriptional activity in A + T and H rats decreased by 34 +/- 11% (P < 0.01) and 61 +/- 4% (P < 0.001), respectively. The observed decreases were greater after H than after A + T, suggesting the possibility that another pituitary hormone plays a role in regulation of cholesterol 7 alpha-hydroxylase. Thyroidectomy alone led to a decrease in cholesterol 7 alpha-hydroxylase specific activity of 37 +/- 7% (P < 0.05) and a trend toward decreased steady-state mRNA levels (21 +/- 12%; P = ns). Adrenalectomy did not significantly decrease cholesterol 7 alpha-hydroxylase specific activity or mRNA levels. Neither thyroidectomy nor adrenalectomy alone affected transcriptional activity. We conclude that under physiologic circumstances, full expression of the cholesterol 7 alpha-hydroxylase gene requires synergistic action of glucocorticoids and thyroid hormone.

Subject

bile-acid biosynthesis; Biochemistry & Molecular Biology; cholesterol; cholesterol 7 alpha-hydroxylase; cultures; gene; gene cyp7; glucocorticoid; hepatic cholesterol; hepatocyte cultures; liver; messenger-rna levels; monolayer-cultures; primary; protein-kinase-c; regulation; sterol 27-hydroxylase; thyroid; thyroid-hormone

Identifier

n/a

Format

Journal Article

URL Address

n/a

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Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

2483-2491

Issue

12

Volume

38

Citation

Pandak W M; Heuman D M; Redford K; Stravitz R T; Chiang J Y L; Hylemon P B; Vlahcevic Z R, “Hormonal regulation of cholesterol 7 alpha-hydroxylase specific activity, mRNA levels, and transcriptional activity in vivo in the rat,” NEOMED Bibliography Database, accessed June 18, 2021, https://neomed.omeka.net/items/show/7755.

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