CAREER: Sphingolipid-Dependent Steroid Hormone Biosynthesis

Georgia Tech Research Corporation, Atlanta GA

Investigators

Abstract

Steroid hormones serve as a major form of communication between different organs and tissues, thereby allowing cells to respond in a coordinated manner to changes in the internal and external environments. In the adrenal cortex, the biosynthesis of these hormones is tightly regulated by the trophic hormone adrenocorticotropin (ACTH) via a cAMP signaling cascade. Exposure of steroidogenic cell types to sphingolipids (SL) has been shown to both increase and decrease steroid hormone biosynthesis. However, the mechanism(s) by which SLs alter steroid hormone secretion is unknown. Preliminary studies using mass spectrometry have found that ACTH (and cAMP) shifts the cellular SL profile and that SLs increase steroidogenic gene expression, suggesting that SLs may play a role in ACTH/cAMP-stimulated steroid hormone biosynthesis in the adrenal cortex. Because steroid hormones enable the body to respond to a wide variety of external stimuli, maintain homeostasis, and undergo developmental and cyclic programs, further investigation into cellular pathways that alter steroid hormone biosynthesis is warranted. Both molecular and biochemical techniques will be employed to examine this novel mechanism by which ACTH/cAMP utilizes SL metabolism in the regulation of adrenocortical steroidogenesis. Broader Impacts: The primary goal of graduate training in the biological sciences is to teach students how to perform, evaluate, and communicate hypothesis-driven research. Furthermore, studies have shown that the earlier pre-college students engage in scientific discovery, the more likely are they to consider careers in the biological sciences. Thus, in addition to increasing our understanding of the pathways that control steroid hormone biosynthesis, carrying out the studies outlined in this project will facilitate the mentoring and training of both graduate and undergraduate students. This project has two additional key objectives: 1) to train students how to assimilate, critique, and communicate data and 2) to expose high school students to careers in academic research. These objectives will be achieved through the development of a course in data analysis and presentation and by engaging high school students in laboratory-based research.