Estrogen biosynthesis and 1beta-hydroxylation using C19 and 19-nor steroid precursors

Abstract

(1) In order to study the relationship between aromatization (estrogen biosynthesis) and 1beta-hydroxylation, the effects of a variety of factors on these processes were evaluated. (2) Using the C18 substrate, 4-estrene-3,17-dione, it was found that carbon monoxide, SU-4885, amphenone B, potassium cyanide, 4-androstene-3,17-dione and 1,4-androstadiene-3,17-dione inhibited the above transformations significantly and to varying degrees. However, within a given experiment the inhibition of each process was similar. (3) SKF-525A did not inhibit either transformation. In addition, phosphate, Tris and barbital buffers, as well as pH changes from 6.9 to 7.7, had no stimulatory or inhibitory effect on the production of estrogen and 1beta-hydroxy compounds. (4) In contrast, several inhibitors affected the aromatization of C19 and C18 steroids differently. These include carbon monoxide, SU-4885 and amphenone B. (5) When a mixture of 4-[7beta-3Hi1estrene-3,17-dione and 19-[4-14C]nortestosterone were incubated together the former was preferentially converted to estrogen. This preference for the 17-keto steroidal form mimics results observed for C19 substrates. (6) We conclude that while estrogen biosynthesis and 1beta-hydroxylation appear to be mediated by the same enzyme system, the same conclusion cannot be drawn for the aromatization of C19 and C18 substrates.

PIP: Estrogen biosynthesis and lbeta-hydroxylation using carbon-19 and 19-nor steroid precursors were evaluated. 4-estrene-3, 17-dione was used to find that carbon monoxide, SU-4885, amphenone B, potassium cyanide, 4-androstene-3,17-dione, and 1,4-androstadiene-3,17-dione inhibited the above transformations to varying degrees. SKF-525A did not inhibit either transformation, and phosphate, Tris and barbital buffers as well as pH changes from 6.9 to 7.7 had no effect on the production of estrogen and lbeta-hydroxy compounds. Carbon monoxide, SU-4885, and amphenone B affected the aromatization of carbon-19 and carbon-18 steroids differently. A mixture of 4 (7 beta-tritium) estrene-3,17-dione and 19-(4-carbon 14) nortestosterone incubated together resulted in the former preferentially converted to estrogen. It is concluded that while estrogen biosynthesis and lbeta-hydroxylation appear to be mediated by the same enzyme system, however, the same conclusion cannot be drawn for the aromatization of carbon-19 and carbon-18 substrates.