Inhibition of human placental progesterone and estrogen synthesis in early human gestation by aminoglutethimide in vivo.
The inhibitory effect of d,l-aminoglutethimide (AG) on the synthesis of progesterone and estradiol in early human pregnancy (8th-12th week of gestation) was investigated in volunteers; control group (n = 11), AG group [1000 mg AG orally at test begin (n = 6)]. Venous blood samples were taken at the beginning of the test and 0.5, 1, 2, 4, 8 and 24 h thereafter. In controls, no significant changes in serum progesterone and estradiol could be observed during 24 h. In the AG group, a decrease in progesterone and estradiol could be observed within 1 h after the test began; lowest serum steroid concentrations were reached after 4 h. Relative to the initial values taken as 100%, the greatest decrease in progesterone ranged between 37 and 83%, 62 +/- 15% (means +/- SD)(n = 6); the greatest decrease in estradiol ranged between 32 and 78%, 51 +/- 17% (means +/- SD)(n = 6). Twenty four hours after AG treatment, both steroids reached similar concentrations to those found at test begin. No clinical signs (e.g. uterine bleeding, contractions) for the abortifacient action of AG were observed. In conclusion, a single dose of AG (1000 mg given orally) cannot induce a therapeutic abortion in early pregnancy. In accordance with in vitro studies, the inhibitory effect of AG on placental progesterone formation is due to an inhibition of mitochondrial cholesterol side chain cleavage. The decrease in estradiol is thought to be related to an inhibition of placental aromatase.
D000616:Aminoglutethimide; D004958:Estradiol / Q000097:blood; D004967:Estrogens / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007700:Kinetics; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011374:Progesterone / Q000096:biosynthesis* / Q000097:blood
D004967:Estrogens; D000616:Aminoglutethimide; D011374:Progesterone; D004958:Estradiol