HUMAN LIVER DEHYDROEPIANDROSTERONE SULFOTRANSFERASE - NATURE AND EXTENT OF INDIVIDUAL VARIATION

Dehydroepiandrosterone sulfotransferase (DHEA ST) catalyzes the sulfat ion of steroid hormones such as DHEA, estrone, and estradiol. As a fir st step in pharmacogenetic studies of DHEA ST in humans, we measured i ndividual variation in DHEA ST enzymatic activity and thermal stabilit y in 94 samples of human hepatic tissue, 39 of which were from patient s with normal liver function studies. Neither level of enzyme activity nor thermal stability were significantly correlated with either time of tissue storage at -80-degrees-C or patient age. In addition, there were no gender-dependent differences in DHEA ST activity in these samp les. DHEA ST enzymatic activity varied 4.6-fold, with a mean value of 317 +/- 100 units/gm tissue (mean +/- SD) in all samples and 318 +/- 1 04 units/gm in the subset of 39 samples from patients with normal hepa tic function studies. Frequency distribution of DHEA ST activity for b oth the entire group of 94 samples and the subset of 39 were bimodal, with 25% and 21% included in a high activity subgroup, respectively. T he presence of this high activity subgroup was confirmed when data for samples from male and female patients were evaluated separately and w hen only data for white patients were examined. The existence of a sub group of subjects with a high level of DHEA ST enzymatic activity in l iver and a 4.6-fold range in this activity have implications for indiv idual differences in the sulfate conjugation of endogenous and exogeno usly administered steroid hormones and raise the possibility of pharma cogenetic regulation of this important enzyme in humans.