Interactions of foetal steroid binding protein with other binding proteins in human serum

Foetal steroid binding protein (FSBP) which is present in normal human serum sometimes exhibits unusual sex-steroid binding; its effects on steroid action are uncertain but potentially important in view of the different levels seen in populations at different risk of breast cancer. Studies of the binding of 5 alpha-dihydrotestosterone to FSBP were conducted at varying concentrations of human serum albumin (HSA) and sex hormone binding globulin (SHBG). The saturable, specific binding of purified FSBP (Ka approximately equal to 5 X 10(8) l/mol), was transformed to a rising, plateau pattern by the addition of HSA. In equilibrium dialysis, FSBP competed with HSA or SHBG in a strictly proportional way when the third protein was absent. In the presence of HSA an initial sharp shift of ligand from SHBG to FSBP was observed with increasing FSBP concentration, but this was reversed as higher levels were reached. Steroid binding by FSBP in vivo may be determined predominantly by its interactions with other binding proteins.