|Smith, Timothy - Tim|
Submitted to: Journal of Steroid Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/1/1996
Publication Date: N/A
Interpretive Summary: Our investigations have defined the existence of isoforms of porcine aromatase which differ both structurally and functionally. At the present time, three isoforms specific to the ovarian tissues (theca and granulosa), term placenta and early blastocyst have been characterized based on these studies and the recent report by Choi et al. Limited data are available on the organization of porcine aromatase at the genomic level. However, curre evidence favors multiple copies, at lease three (ovarian, placental and blastocyst), in addition to alternatively-spliced untranslated exons, all o which appear to be tightly clustered on chromosome 1. Definitive proof awaits the complete sequence characterization of this genomic region.
Technical Abstract: Aromatase cytochrome P450 (P450arom) is expressed in a variety of tissues. Pigs express P450arom as bilaminar blastocysts in utero, and thereafter in the gonads, adrenal glands and placenta. Our studies also demonstrate the existence of porcine isozymes of P450arom which differ substantially in their amino acid composition and function. The placental isoform, most similar to P450arom in other mammals consists of 503 amino acids. The ovarian isoform, expressed in both theca and granulosa cells, is a 501 amino acid protein exhibiting < 20% of the activity of the placental isozyme. Furthermore, it is inhibited not only by CGS 16949A but also etomidate which does not inhibit the placental P450arom. Partial sequences generated by the RACE procedure indicate that the expression of a third isoform in the blastocyst is switched to the placental isozyme during differentiation of the fetal membranes. In addition, these transcripts and others from the theca, granulosa, testes, adrenal glands and placenta demonstrate differences in the 5'-untranslated sequence was obtained from transcripts expressed in theca and granulosa. Testes and adrenal transcripts also have identical 5' ends which differ substantially from the ovarian sequence. Blastocyst and placenta 5'-untranslated sequences differ from each other and from those expressed in the gonads and adrenals. Thus, several tissue-specific transcripts encode porcine p450arom.