Ovarian enzymatic divergence in patients with polycystic ovary syndrome excreting urinary pregnanetriolone.
When ovarian mitochondria from patients with polycystic ovary syndrome (POS) were incubated with [7-3H]17alpha-hydroxypregnenolone and [4-14C]-17alpha-hydroxyprogesterone, 11beta-hydroxylated metabolites were obtained. The mitochondria, prepared from pooled, frozen, polycystic ovarian tissue of 5 patients, converted [7-3H]17alpha-hydroxypregnenolone to 3beta, 11beta, 17alpha--trihydroxy-5-pregnen-20-one (yield 0.065%) and to 3beta, 17alpha-dihydroxy-5-pregnene-11,20-dione (0.22%), while [4-14C]17alpha-hydroxyprogesterone was converted to 21-deoxycortisol (0.1%). Incubation of mitochondria, prepared from 4 pooled samples of frozen, normal ovarian tissue, yielded no evidence of 11beta-hydroxylation of either of the substrates. Mitochondria obtained from fresh, polycystic ovarian tissue of a single patient with POS converted [7-3H]17alpha-hydroxypregnenolone to 3beta,17alpha-dihydroxy-5-pregnene-11,20-dione (2.1%) and [4-14C]17alpha-hydroxyprogesterone to 21-deoxycortisol (0.1%). When the same mitochondrial preparation was incubated simultaneously with [7-3H]17alpha-hydroxypregnenolone and [4-14C]11-deoxycortisol, it converted 17alpha-hydroxypregnenolone to 3beta,17alpha-dihydroxy-5-pregnene-11,20-dione (1.9%), but no 11beta-hydroxylated derivatives of 11-deoxycortisol were found. These results demonstrate that ovaries of patients with POS contain an 11beta-hydroxylase active towards C-21-deoxysteroids but inert to C-21-hydroxysteroids such as 11-deoxycortisol.
D006907:17-alpha-Hydroxypregnenolone / Q000378:metabolism; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000096:biosynthesis; D006900:Hydroxylation; D006908:Hydroxyprogesterones / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010053:Ovary / Q000201:enzymology*; D011085:Polycystic Ovary Syndrome / Q000201:enzymology* / Q000378:metabolism / Q000652:urine; D011279:Pregnanetriol / Q000652:urine*; D011283:Pregnenes / Q000096:biosynthesis
D006908:Hydroxyprogesterones; D011283:Pregnenes; D011279:Pregnanetriol; D006907:17-alpha-Hydroxypregnenolone; D006899:Mixed Function Oxygenases; D006854:Hydrocortisone