Human liver dehydroepiandrosterone sulfotransferase: nature and extent of individual variation.
Dehydroepiandrosterone sulfotransferase (DHEA ST) catalyzes the sulfation of steroid hormones such as DHEA, estrone, and estradiol. As a first step in pharmacogenetic studies of DHEA ST in humans, we measured individual variation in DHEA ST enzymatic activity and thermal stability in 94 samples of human hepatic tissue, 39 of which were from patients 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 samples. 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 +/- 104 units/gm in the subset of 39 samples from patients with normal hepatic function studies. Frequency distributions of DHEA ST activity for both the entire group of 94 samples and the subset of 39 were bimodal, with 25% and 21% included in a high activity subgroup, respectively. The presence of this high activity subgroup was confirmed when data for samples from male and female patients were evaluated separately and when only data for white patients were examined. The existence of a subgroup of subjects with a high level of DHEA ST enzymatic activity in liver and a 4.6-fold range in this activity have implications for individual differences in the sulfate conjugation of endogenous and exogenously administered steroid hormones and raise the possibility of pharmacogenetic regulation of this important enzyme in humans.
Aksoy
I A
IA
Department of Pharmacology, Mayo Medical School/Mayo Clinic/Mayo Foundation, Rochester, MN 55905.
Sochorová
V
V
Weinshilboum
R M
RM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D004795:Enzyme Stability; D005260:Female; D006358:Hot Temperature; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D015238:Sulfotransferases / Q000378:metabolism*
D015238:Sulfotransferases; C019998:dehydroepiandrosterone sulfotransferase