| Although primarily regarded as a sex steroid, estrogen plays an important role in many other physiological processes including adipose development and disposition. Fluctuations in estrogen levels, such as those observed in premenopausal and postmenopausal women, rearrange the distribution of adipose tissue. Epidemiological studies have also suggested that sex steroids are responsible for the difference in adipose tissue distribution between men and women. The difference in adipose distribution can be a cause of major concern, since centrally distributed fat confers a greater risk of obesity-related morbidity, such as cardiovascular disease and diabetes. While sex steroids have been implicated in adipose tissue function and distribution, little is known about the regulation of sex steroids in adipose tissue. In this study, we examine the expression and function of an important estrogen regulator, estrogen sulfotransferase (EST), in adipose tissue. EST regulates estrogen activity by catalyzing the sulfoconjugation and inactivation of estrogens. We have found that EST is expressed in a sexually dimorphic manner in select male mouse white adipose tissues while completely absent in female adipose. EST expression is dependent on testosterone in male mice; treating female mice with testosterone induced expression. We demonstrate that EST has a functional role in regulating adipose tissue, as EST knockout mice develop increased epididymal fat with enlarged adipocyte size. Finally, we describe the generation of two mouse models, an adipose and a liver transgenic, to further study the tissue expression of EST. We characterize EST expression in adipose (aP2-EST) transgenic mice and find it functions in regulating adipose accumulation, similar to what is seen in wild-type male mice. In addition, EST adipose expression was found to possibly play a role in regulating estrogen response in the uterus. Our second model describes the generation of a mouse transgenic expressing EST in the liver; however, we were unable to establish a line consistently expressing high levels of EST. In summary, we find EST is expressed in white adipose tissues in a sexually dimorphic manner, is regulated by testosterone, plays a physiological role in regulating adipose tissue, and describe the generation of two transgenic mouse models. |
