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ARS Home » Plains Area » Clay Center, Nebraska » U.S. Meat Animal Research Center » Livestock Bio-Systems » Research » Publications at this Location » Publication #164587
Title: PARALOGUES OF PORCINE AROMATASE CYTOCHROME P450: A NOVEL HYDROXYLASE ACTIVITY IS ASSOCIATED WITH THE SURVIVAL OF A DUPLICATED GENE

Author
item CORBIN, CYNTHIA - UNIV CALIFORNIA, DAVIS
item MAPES, SAMANTHA - UNIV CALIFORNIA, DAVIS
item MARCOS, JOSEP - CHILDRENS HOSP OAKLAND CA
item SHACKLETON, CEDRIC - CHILDRENS HOSP OAKLAND CA
item MORROW, DEREK - TEXAS A&M UNIV, COLL STN
item SAFE, STEPHEN - TEXAS A&M UNIV, COLL STN
item Wise, Thomas
item Ford, Johny
item CONLEY, ALAN - UNIV CALIFORNIA, DAVIS

Submitted to: Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/27/2004
Publication Date: 5/1/2004
Citation: CORBIN, C.J., MAPES, S.M., MARCOS, J., SHACKLETON, C.H., MORROW, D., SAFE, S.H., WISE, T., FORD, J.J., CONLEY, A.J. 2004. Paralogues of porcine aromatase cytochrome p450: A novel hydroxylase activity is associated with the survival of a duplicated gene. Endocrinology. 145(5):2157-2164.

Interpretive Summary: The aromatase P450 enzyme functions to control the balance of a major sex steroid, estrogen and has a major impact on the reproductive process. The pig is unique among mammals in having more then one P450aromatase gene (CYP19) which are tissue specific in expression: gonad and adrenal, endometrial and placental, and blastocysts and embryonic forms. Analysis of testosterone metabolism by porcine gonadal P450 aromatase by thin layer chromatography, gas chromatography and mass spectrometry has identified a metabolite unique to expected intermediates and estrogens and was identified as 1-hydroxy-testosterone. 1-hydroxy-testosterone is not metabolized to estrogens, produced in levels comparable to estradiol and activated the androgen receptor equally as well as dihydrotestosterone. These unique aspects of 1-hydroxy-testosterone supports an important physiological role for this steroid in males and females that remains to be elucidated. Further analysis of the role of 1-hydroxy-testosterone may be important in understanding porcine gonadal function and increasing reproductive efficiency. The results also may indicate that the process of steroidogenesis is still evolving from original enzymes by duplication of genes encoding them followed by a divergence of catalytic function among those that survive and are fixed in the gene pool.

Technical Abstract: Reproductive success in vertebrates is absolutely dependent on estrogens as the final products in sex steroid synthesis from cholesterol. Enzymes of the cytochrome P450 superfamily form the backbone of this metabolic cascade, catalyzing the formation of all major classes of steroid hormones but how the pathway evolved is unknown. Estrogen is synthesized by an evolutionarily ancient enzyme, aromatase cytochrome P450 (P450arom), and is uniquely positioned to control the balance of sex steroids and the reproductive process. It is highly conserved and likely under heavy selection pressure. The existence of distinct placenta- and gonad-specific forms of the P450arom enzyme was therefore an unexpected finding when first made in the pig. Similar gene duplications also gave rise to paralogues of P450arom in fish, but adaptive functions have yet to be identified. Here we show that the gonad-specific paralogue of porcine P450arom exhibits a novel activity, catalyzing the synthesis of a novel potent androgen. This demonstrates that steroid hormone biosynthesis in vertebrates is a dynamic process still evolving by functional divergence arising in paralogues of the terminal enzymes in steroidogenic pathways.