Paralogues of porcine aromatase cytochrome P450: A novel hydroxylase activity is associated with the survival of a duplicated gene

C. Jo Corbin, S. M. Mapes, J. Marcos, C. H. Shackleton, D. Morrow, S. Safe, T. Wise, J. Joe Ford, Alan J Conley

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

The gonadal and placental paralogues of porcine aromatase cytochrome P450 (P450arom) were examined for novel catalytic properties to shed light on the evolutionary survival of duplicated copies of an enzyme critical to reproduction. Recombinant gonadal P450arom catalyzed the formation of a novel metabolite from testosterone, identified by gas chromatography/mass spectrometry and biochemical analyses as 1β-hydroxytestosterone (1βOH-T), in almost equal proportion to 17β-estradiol (E2). This activity was absent in reactions with the porcine placental paralogue (or other orthologues) of P450arom and was minimal with androstenedione. Incubations with both porcine enzymes and with bovine and human P450arom demonstrated that 1βOH-T was not aromatizable, and 1βOH-T activated the androgen receptor of prostate cancer cells in vitro. Porcine testicular and follicular granulosa tissues synthesized 1βOH-T, which was also detected in testicular venous plasma. These results constitute the first of identification of a novel, perhaps potent, nonaromatizable metabolite of testosterone, whose synthesis (paradoxically) can be definitively ascribed to the activity of the gonadal paralogue of porcine P450arom. It probably represents an evolutionary gain of function associated with fixation and the survival of the genes after CYP19 duplication. Novel activities and adaptive functions may exist among other duplicated vertebrate aromatases.

Original languageEnglish (US)
Pages (from-to)2157-2164
Number of pages8
JournalEndocrinology
Volume145
Issue number5
DOIs
StatePublished - May 2004

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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