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Molecular Pharmacology, Vol 18, 543-549, Copyright © 1980 by the American Society for Pharmacology and Experimental Therapeutics

Neonatal Imprinting and Hepatic Cytochrome P-450

I. Comparison of Testosterone Hydroxylation in a Reconstituted System between Neonatally Imprinted and Nonimprinted Rats

LELAND W. K. CHUNG 1 and HAIYEN CHAO 1

1 Pharmacology/School of Pharmacy, University of Colorado, Boulder, Colorado 80309

Rat hepatic microsomal cytochrome P-450s were resolved by DEAE-cellulose column chromatography. A comparison was made between the elution profiles of the cytochrome P-450 from the neonatally imprinted (adult male and adult male castrated at 4 weeks of age) and nonimprinted (adult female and adult male castrated at birth) rats. Four peaks of cytochrome P-450 (designated peaks I, II, III, and IV) were eluted by a linear salt gradient from 0 to 0.25 M NaCl. No consistent qualitative difference was found in the elution profiles of cytochrome P-450 from the solubilized microsomes of these rats. However, further resolution of the catalytic activities of the various peaks of cytochrome P-450 in a reconstituted system revealed a form or forms of cytochrome P-450 in the peak II fraction that can be imprinted by gonadal hormones during the neonatal period. Only the form of cytochrome P-450 isolated from the neonatally imprinted animals was capable of hydroxylating testosterone at the 16agr position to a significant degree similar to that reported for the intact microsomes. Phenobarbital treatment enhanced the total as well as the various peaks of cytochrome P-450 content in the hepatic microsomes of both adult male and female rats. Cytochrome P-450 content in peak III/IV, however, was differentially induced by the phenobarbital treatment. This differentially induced form or forms of cytochrome P-450 hydroxylated testosterone in a reconstituted system at the 16agr but not at the 7agr or 6beta positions.

Note:
ACKNOWLEDGMENTS This study was formulated during LWKC’s tenure at McGill University. The excellent secretarial help from Ms. Pamela Lingenfelter and the critical reading of the manuscript by Dr. Richard J. Kraemer are appreciated.

Submitted on January 17, 1980
Accepted on June 10, 1980




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[Abstract] [Full Text]


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