Expression and roles of steroidogenic acute regulatory (StAR) protein in ‘non-classical’, extra-adrenal and extra-gonadal cells and tissues

• Published in: Molecular and cellular endocrinology 2013-05, Vol.371 (1-2), p.47-61
• Main Authors: Anuka, Eli, Gal, Michael, Stocco, Douglas M., Orly, Joseph
• Format: Article
• Language: English
• Subjects: Adrenal Cortex - metabolism; adrenal cortex hormones; Adrenal Cortex Hormones - biosynthesis; Constraining; Endothelium, Vascular - metabolism; Gonadal Steroid Hormones - biosynthesis; Gonads; Gonads - metabolism; Hormones; Human; Humans; Liver - metabolism; Macrophages - metabolism; Neoplasms - metabolism; Non-steroidogenic StAR activity; Organs; Phosphoproteins - analysis; Phosphoproteins - biosynthesis; Phosphoproteins - metabolism; Placenta; Proteins; StAR expression; steroid hormones; Steroids; Steroids - biosynthesis; tissues; ‘Non-classical’ steroidogenic cells
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2013.02.003

► ‘Non-classical’ StAR facilitates steroidogenesis or other mitochondrial activities. ► Steroidogenic StAR affects development and protects against cytotoxic insults. ► In transformed cells, steroidogenic StAR allows escape from tumor immunity. ► StAR can enhance bile acid production and synthesis of regulatory oxysterols. ► StAR can also confer anti-apoptotic robustness and chemotherapy resistance. The activity of the steroidogenic acute regulatory (StAR) protein is indispensable and rate limiting for high output synthesis of steroid hormones in the adrenal cortex and the gonads, known as the ‘classical’ steroidogenic organs (StAR is not expressed in the human placenta). In addition, studies of recent years have shown that StAR is also expressed in many tissues that produce steroid hormones for local use, potentially conferring some functional advantage by acting via intracrine, autocrine or paracrine fashion. Others hypothesized that StAR might also function in non-steroidogenic roles in specific tissues. This review highlights the evidence for the presence of StAR in 17 extra-adrenal and extra-gonadal organs, cell types and malignancies. Provided is the physiological context and the rationale for searching for the presence of StAR in such cells. Since in many of the tissues the overall level of StAR is relatively low, we also reviewed the methods used for StAR detection. The gathered information suggests that a comprehensive understanding of StAR activity in ‘non-classical’ tissues will require the use of experimental approaches that are able to analyze StAR presence at single-cell resolution.