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 steroids in the plasma, is increased in subjects with endocrine-dependent tumours. However, little is known about factors which influence the distribution of these hormones in plasma. In order to investigate this, 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 decrease (up to 38% from basal values) in the fraction of testosterone not bound to sex-hormone binding globulin (non-SHBG bound testosterone). The decrease in the non-SHBG bound testosterone fraction was accompanied by an increase (up to 20% from basal values) in the non-SHBG bound 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 male subjects resulted in a similar decrease in the non-SHBG bound testosterone fraction to that occurring in vivo after cortisol infusion or ACTH injection. In contrast dexamethasone, which unlike cortisol does not bind to cortisol binding globulin (CBG), had no effect on the distribution of testosterone in plasma. It is concluded from these in vivo and in vitro studies that cortisol is able to displace testosterone from CBG and that changes in plasma concentrations of cortisol alter the distribution of testosterone and oestradiol in plasma. Short term changes in the distribution of testosterone in plasma that result from the infusion of cortisol OF ACTH injection do not appear to influence the production of 3 alpha androstanediol glucuronide.