Multiple Signaling Pathways Coordinate CYP17 Gene Expression in the Human Adrenal Cortex
Marion B. Sewer*, Donghui Li, Eric B. Dammer, Srinath Jagarlapudi and Natasha Lucki
School of Biology and Parker H. Petit Institute for Bioengineering & Biosciences,
Georgia Institute of Technology, Atlanta, GA 30332-0230
* Corresponding author: email@example.com
Optimal levels of steroid hormone biosynthesis are assured by the integration of several regulatory mechanisms, including substrate delivery, enzymatic activity, and gene transcription. In the human adrenal cortex, optimal glucocorticoid secretion is achieved by the actions of adrenocorticotropin (ACTH), which exerts transcriptional pressure on all genes involved in steroidogenesis. One of these genes is CYP17, which encodes P450 17α-hydroxylase-17,20 lyase, a key enzyme in the production of cortisol and adrenal androgens. Levels of CYP17 transcription are regulated by multiple regulatory mechanisms that act to respond to various signaling cues. These cues are coordinated in a developmental, species-, and tissue-specific manner, with an additional time/circadian-dependent level of regulation. This brief review will highlight some of the signal transduction cascades and transcription factors that have been shown to modulate CYP17 gene expression in the adrenal cortex.
Keywords: CYP17, adrenocorticotropin, angiotensin II, cAMP, steroid hydroxylase, steroidogenic factor-1, PKA