This Article Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by BARBIERI, R. L. Articles by RYAN, K. J. Search for Related Content PubMed PubMed Citation Articles by BARBIERI, R. L. Articles by RYAN, K. J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ETHINYLESTRADIOL NORETHINDRONE OXYGEN SODIUM BOROHYDRIDE

Aromatization of Norethindrone to Ethinyl Estradiol by Human Placental Microsomes^*

Laboratory of Human Reproduction and Reproductive Biology and the Department of Obstetrics and Gynecobgy, Brigham and Women's Hospital, Harvard Medical School Boston, Massachusetts 02115

Address requests for reprints to: Dr. Robert L. Barbieri, 45 Shattuck Street, Boston, Massachusetts 02115.

The interaction of 19-norethindrone [4-estren-17-ethinyl-17β-ol, 3-one (NET)] with human placental micro-somes was investigated using enzymatic and spectral techniques. The incubation of [6, 7-³H]norethindrone with human placental microsomes, NADPH, and molecular oxygen resulted in the production of ethinyl estradiol [l,3,5-(10)estratrien-17-ethinyl-3,17β-diol (EE)]. The reaction was linear with respect to time and protein concentration. Androstenedione inhibited the enzymatic aromatization of NET to EE. The product was identified by thin layer chromatography, recrystallization to constant specific activity, and derivative formation. No acid or base was used in any step of product identification. To ensure that spontaneous aromatization of metabolites of NET did not contribute to our results, representative samples were treated with sodium boro-hydride before processing. Sodium borohydride reduces the 4-en-3-one grouping of the A-ring, thereby preventing chemical aromatization. Sodium borohydride treatment did not reduce our observed yields of EE from NET. The addition of NET to a preparation of solubilized, partially purified placental microso-mal cytochrome P-450 yielded a type I cytochrome P-450 binding spectrum. The apparent spectral dissociation constant for NET binding to cytochrome P-450 was 28 µM. These results suggest that NET is enzymatically aromatized to EE by human placental microsomes.

^* This work was supported in part by USPHS Grant 2-SO7 RR-05481-10. Presented in part at the 64th Annual Meeting of The Endocrine Society, San Francisco, CA, June 1982.

Received December 6, 1982.