THE INFLUENCE OF STRESS-RELATED FACTORS ON THE DISTRIBUTION OF SEX STEROIDS IN PLASMA - IMPLICATIONS FOR ENDOCRINE-DEPENDENT CANCERS

There is evidence that the free, biologically active fraction of sex s teroids in the plasma, is increased in subjects with endocrine-depende nt tumours. However, little is known about factors which influence the distribution of these hormones in plasma. In order to investigate thi s, cortisol (14 mu M) was infused, or ACTH (Synacthen, 250 mu g, i.v.) was injected into male subjects and this resulted in a significant de crease (up to 38% from basal values) in the fraction of testosterone n ot bound to sex-hormone binding globulin (non-SHBG bound testosterone) . The decrease in the non-SHBG bound testosterone fraction was accompa nied by an increase (up to 20% from basal values) in the non-SHBG boun d oestradiol fraction after ACTH injection. No significant changes in the unbound concentrations of testosterone or oestradiol were detected . The addition of cortisol (250 nM) to a plasma pool obtained from mal e subjects resulted in a similar decrease in the non-SHBG bound testos terone fraction to that occurring in vivo after cortisol infusion or A CTH injection. In contrast dexamethasone, which unlike cortisol does n ot bind to cortisol binding globulin (CBG), had no effect on the distr ibution of testosterone in plasma. It is concluded from these in vivo and in vitro studies that cortisol is able to displace testosterone fr om CBG and that changes in plasma concentrations of cortisol alter the distribution of testosterone and oestradiol in plasma. Short term cha nges in the distribution of testosterone in plasma that result from th e infusion of cortisol OF ACTH injection do not appear to influence th e production of 3 alpha androstanediol glucuronide.