EFFECTS OF GENDER AND PREGNANCY ON HEPATOCELLULAR UPTAKE OF PALMITIC ACID - FACILITATION BY ALBUMIN

The human serum albumin (HSA)-dependent unbound clearance (Cl-u) of [H -3]palmitic acid (PA) by hepatocyte suspensions isolated from immature and mature male and female and pregnant female rats was studied. The Cl-u values obtained experimentally were compared with the predictions of a noncompartmental diffusion-reaction (Bass-Pond) theory for the c ellular uptake of protein-bound ligands. In all groups, as the concent ration of HSA (C-a) was increased, there was a striking increase in Cl -u. These enhancement factors were predicted by the theory. Adult fema les had higher Cl-u values at high C-a values than males or immature f emales. Furthermore, at high C-a values, Cl-u in pregnant animals was twice as high as in the nonpregnant animals and four times as high as in the aged-matched males. The absolute values of Cl-u obtained experi mentally in both pregnant and nonpregnant females exceeded the maximal predictions of the theory, using reasonable values of all of the para meters. Thus, according to current data on the physicochemical charact eristics of the uptake system, the study demonstrates that some specia lized process exists to facilitate hepatocellular uptake of fatty acid from albumin, and that it is potentiated by the female sex hormones.