Metabolism of pregnenolone by human breast cancer. Evidence for 17 alpha-hydroxylase and 17,20-lyase.
The metabolism of 7-(3)H-pregnenolone was studied in vitro using 16 human breast carcinomas. All mammary tumors transformed pregnenolone to progesterone. All estrogen receptor poor tumors and 4 out of 8 estrogen receptor rich tumors converted pregnenolone to 17-hydroxypregnenolone. Five estrogen receptor poor tumors showed the presence of 17,20-lyase as evidenced by formation of dehydroepiandrosterone and androstenedione. In two estrogen receptor poor tumors, conversions of pregnenolone to progesterone, 17-hydroxy pregnenolone, dehydroepiandrosterone, androstenedione and finally to estradiol was documented, providing a hypothetical pathway for steroid metabolism in human breast cancer. The conversion of pregnenolone to 17-hydroxypregnenolone was significantly less in receptor rich tumors and was totally absent in 4 receptor rich tumors with estrogen receptors of over 45 fmol/mg protein.
D006907:17-alpha-Hydroxypregnenolone / Q000096:biosynthesis; D000368:Aged; D000446:Aldehyde-Lyases / Q000378:metabolism*; D000735:Androstenedione / Q000096:biosynthesis; D001943:Breast Neoplasms / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System; D003687:Dehydroepiandrosterone / Q000096:biosynthesis; D004958:Estradiol / Q000096:biosynthesis; D005260:Female; D006801:Humans; D006908:Hydroxyprogesterones / Q000378:metabolism; D008593:Menopause; D008875:Middle Aged; D011284:Pregnenolone / Q000378:metabolism*; D011374:Progesterone / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000502:physiology; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism*; D013250:Steroid Hydroxylases / Q000378:metabolism*
D006908:Hydroxyprogesterones; D011960:Receptors, Estrogen; D006907:17-alpha-Hydroxypregnenolone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D011374:Progesterone; D004958:Estradiol; D011284:Pregnenolone; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D013254:Steroid 17-alpha-Hydroxylase; C022433:pregnenolone 17-alpha-hydroxylase; D000446:Aldehyde-Lyases