Gender-Specific Expression and Mechanism of Regulation of Estrogen Sulfotransferase in Adipose Tissues of the Mouse

Although primarily regarded as a sex steroid, estrogen plays an important role in many other physiological processes including adipose development and disposition. Estrogen sulfotransferase (EST) regulates estrogen activity by catalyzing the sulfoconjugation and inactivation of estrogens. In the present study, we report the gender-specific expression of EST in adipose tissues of the mouse and describe contrasting mechanisms of EST regulation in the fat and liver. EST is expressed in the white adipose tissues of the male but not female mouse. Within the various fat depots of male mice, it is most abundantly expressed in the epididymal fat pad, with variable levels in other white fats and no expression in the brown fat. Fractionation of epididymal fat cells showed EST to be predominantly associated with stromal vascular cells (preadipocyte). EST expression in male mouse adipose tissues is dependent on testosterone as castration ablated, and administration of exogenous testosterone restored, EST expression. Furthermore, testosterone treatment induced abnormal EST expression in the parametrial fat of female mice. EST induction by testosterone in female mice is tissue specific because testosterone treatment had no effect on liver EST expression. Conversely, the liver X receptor agonist TO-901317 induced EST expression in female mouse liver but not in their adipose tissues. Finally, we demonstrate that male EST knockout mice developed increased epididymal fat accumulation with enlarged adipocyte size. We conclude that EST is expressed in adipose tissues in a sexually dimorphic manner, is regulated by testosterone, and plays a physiological role in regulating adipose tissue accumulation in male mice.