Effects of progesterone, progestogens, and danazol on the specific cortisol binding in human plasma.
The interaction of medroxyprogesterone acetate (MPA) with cortisol binding to corticosteroid-binding globulin (CBG) was studied with the use of an aqueous two-phase system with polyethylene glycol and dextran for equilibrium partition. Competitive binding analyses were also performed for progesterone (P), levonorgestrel, norethisterone, danazol, and tamoxifen. P and danazol were found to exert cortisol displacing activity, whereas MPA and the other tested compounds had no such effect. The glucocorticoid effects reported for MPA could not be explained by displacement. In general, P serum concentrations are lower than those of cortisol, and most binding sites on CBG are occupied by the glucocorticoid. At high P levels displacement and an increase in free cortisol may occur. Danazol displacement of cortisol is hampered by its pronounced albumin binding. In conclusion, none of the tested compounds should increase free and biologically active cortisol during normal clinical treatment.
Ottosson
U B
UB
Nilsson
B
B
Södergård
R
R
von Schoultz
B
B
D001667:Binding, Competitive; D003613:Danazol / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008297:Male; D008525:Medroxyprogesterone / Q000031:analogs & derivatives / Q000378:metabolism; D017258:Medroxyprogesterone Acetate; D011245:Pregnadienes / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism*; D011372:Progestins / Q000378:metabolism*; D013629:Tamoxifen / Q000378:metabolism; D014156:Transcortin / Q000378:metabolism*
D011245:Pregnadienes; D011372:Progestins; D013629:Tamoxifen; D011374:Progesterone; D014156:Transcortin; D017258:Medroxyprogesterone Acetate; D008525:Medroxyprogesterone; D003613:Danazol; D006854:Hydrocortisone