Relative binding affinity of norgestimate and other progestins for human sex hormone-binding globulin.
The relative binding affinity of norgestimate for human sex hormone-binding globulin was compared with that of its metabolites and other progestins by measuring their abilities to displace [3H]testosterone from this carrier protein in vitro. Norgestimate and its 17-deacetylated and 3-keto metabolites did not significantly displace [3H]testosterone from sex hormone-binding globulin at concentrations up to 10,000 nM, whereas gestodene, levonorgestrel, and 3-keto desogestrel displaced [3H]testosterone from sex hormone-binding globulin with IC50 concentrations of 23.1, 53.4, and 91.0 nM, respectively. Since it is believed that a progestin may exert androgenic effects by displacing testosterone from sex hormone-binding globulin, thereby increasing circulating levels of free, active testosterone, these data are consistent with the results of preclinical and clinical studies demonstrating the selective progestational activity of norgestimate.
Phillips
A
A
R. W. Johnson Pharmaceutical Research Institute, Ortho Pharmaceutical Corporation, Raritan, New Jersey 08869.
Hahn
D W
DW
McGuire
J L
JL
D001667:Binding, Competitive; D017135:Desogestrel; D006801:Humans; D016912:Levonorgestrel; D009644:Norgestrel / Q000031:analogs & derivatives* / Q000378:metabolism; D009652:Norpregnenes / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism; D011372:Progestins / Q000378:metabolism*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism
D009652:Norpregnenes; D011372:Progestins; D012738:Sex Hormone-Binding Globulin; C033273:Gestodene; C044815:etonogestrel; D009644:Norgestrel; D013739:Testosterone; D011374:Progesterone; D016912:Levonorgestrel; D017135:Desogestrel; C017576:norgestimate