The effect of the aromatase inhibitor, rogletimide (pyridoglutethimide), on guinea pig adrenal cell steroidogenesis and placental microsomal aromatase activity: comparison with aminoglutethimide and CGS 16949A.
A dispersed guinea pig adrenal system has been used to study the effect of the aromatase inhibitor rogletimide (RGL) on adrenal steroidogenesis. The ACTH-stimulated release of cortisol, 17-hydroxyprogesterone (17-OHP) and androstenedione (A) was measured following exposure of adrenal cells to RGL, or the other aromatase inhibitors aminoglutethimide (AG) and CGS 16949A. RGL at concentrations sufficient to cause 80-90% inhibition of placental microsomal aromatase had no effect on the release of all three steroids. In contrast, AG at 10(-5) M markedly reduced the output of all three steroids from these cells. CGS 16949A at 10(-6) M reduced the output of cortisol and increased the concentration of 17-OHP and A. These results indicate that RGL is unlikely to cause the suppression of cortisol synthesis which has been noted to occur with AG and CGS 16949A during the treatment of breast cancer patients.
Newton
C J
CJ
Department of Academic Biochemistry, Royal Marsden Hospital, London, England.
Mehta
A
A
Dowsett
M
M
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000616:Aminoglutethimide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D001141:Aromatase / Q000378:metabolism*; D047072:Aromatase Inhibitors; D017316:Fadrozole; D005260:Female; D006168:Guinea Pigs; D006854:Hydrocortisone / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008861:Microsomes / Q000201:enzymology*; D009570:Nitriles / Q000494:pharmacology*; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D013256:Steroids / Q000378:metabolism*
D047072:Aromatase Inhibitors; D007093:Imidazoles; D009570:Nitriles; D013256:Steroids; D000616:Aminoglutethimide; C049837:rogletimide; D000324:Adrenocorticotropic Hormone; D001141:Aromatase; D017316:Fadrozole; D006854:Hydrocortisone