Novel method of evaluating biological 19-hydroxylation and aromatization of androgens.
[19C3H]Androstenedione of high specific activity has been prepared. In liver incubation the isotope was shown to be stable to biological processes other than 19-hydroxylation. Incubation of the new substrate with human placental microsomes yielded 3H2O, 3HCOOH and estrogens devoid of radioactivity. The formation of 3H2O and 3HCOOH was close to the expected 2:1 ratio indicating that the material can be used to discriminate between 19-hydroxylation which yields 3H2O and aromatization which results in 3HCOOH. Comparison of the formation of 3H2O from [1 beta, 2 beta 3H]androstenedione and of 3HCOOH from [19C3H3]androstenedione in placental microsomal incubation showed that the aromatization of the former was 3.2 times faster indicating an isotope effect of that magnitude for the aromatization of [19C3H] vs [19CH3]androstenediones. The new substrate will be an effective probe and discriminant of both 19-hydroxylation and aromatization of androgens in vivo and in vitro, reactions which have been reported to be dissociated in specific tissues.
D000728:Androgens / Q000378:metabolism*; D000735:Androstenedione / Q000378:metabolism; D000818:Animals; D001141:Aromatase / Q000378:metabolism*; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism; D008861:Microsomes / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D013250:Steroid Hydroxylases / Q000378:metabolism*
D000728:Androgens; D000735:Androstenedione; D010088:Oxidoreductases; D013250:Steroid Hydroxylases; C027110:steroid 19-hydroxylase; D001141:Aromatase