Cyclosporine and bromocriptine-induced suppressions of CYP3A1/2 and CYP2C11 are not mediated by prolactin

• Published in: European journal of pharmacology 2004-10, Vol.501 (1), p.215-224
• Main Authors: Lu, Shirley K., Callahan, Shellie M., Jin, Runyan, Brunner, Lane J.
• Format: Article
• Language: English
• Subjects: Animals; Aryl Hydrocarbon Hydroxylases - antagonists & inhibitors; Aryl Hydrocarbon Hydroxylases - metabolism; Biological and medical sciences; Bromocriptine; Bromocriptine - pharmacology; Cyclosporine; Cyclosporine - pharmacology; Cytochrome P-450 CYP3A; Cytochrome P450; Cytochrome P450 Family 2; Drug metabolism; Enzyme Inhibitors - pharmacology; Male; Medical sciences; Membrane Proteins - antagonists & inhibitors; Membrane Proteins - metabolism; Microsomes, Liver - drug effects; Microsomes, Liver - metabolism; Pharmacology. Drug treatments; Prolactin; Prolactin - physiology; Rats; Rats, Sprague-Dawley; Steroid 16-alpha-Hydroxylase - antagonists & inhibitors; Steroid 16-alpha-Hydroxylase - metabolism
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2004.08.019

The purpose of this study was to determine if the suppression of hepatic CYP3A1/2 (cytochrome P450 3A1/2) and CYP2C11 (cytochrome P450 2C11) by cyclosporine is mediated by prolactin. Male intact rats were given subcutaneous doses of either 15 mg/kg/day of cyclosporine or 1 ml/kg/day of cyclosporine vehicle concomitantly with one of the following: 500 mg/kg prolactin, 1 ml/kg prolactin vehicle, 4 mg/kg bromocriptine, or 1 ml/kg bromocriptine vehicle for 14 days. Protein expressions were measured using Western blot analysis and activities were measured using an in vitro testosterone hydroxylation assay. The administration of prolactin did not significantly alter CYP3A1/2 protein expression. Hypoprolactinemia, produced by bromocriptine, caused a significant suppression of CYP3A1/2 activity levels when bromocriptine was administered alone and in combination with cyclosporine ( P