Cellular cholesterol delivery, intracellular processing and utilization for biosynthesis of steroid hormones

Abstract

Steroid hormones regulate diverse physiological functions such as reproduction, blood salt balance, maintenance of secondary sexual characteristics, response to stress, neuronal function and various metabolic processes. They are synthesized from cholesterol mainly in the adrenal gland and gonads in response to tissue-specific tropic hormones. These steroidogenic tissues are unique in that they require cholesterol not only for membrane biogenesis, maintenance of membrane fluidity and cell signaling, but also as the starting material for the biosynthesis of steroid hormones. It is not surprising, then, that cells of steroidogenic tissues have evolved with multiple pathways to assure the constant supply of cholesterol needed to maintain optimum steroid synthesis. The cholesterol utilized for steroidogenesis is derived from a combination of sources: 1) de novo synthesis in the endoplasmic reticulum (ER); 2) the mobilization of cholesteryl esters (CEs) stored in lipid droplets through cholesteryl ester hydrolase; 3) plasma lipoprotein-derived CEs obtained by either LDL receptor-mediated endocytic and/or SR-BI-mediated selective uptake; and 4) in some cultured cell systems from plasma membrane-associated free cholesterol. Here, we focus on recent insights into the molecules and cellular processes that mediate the uptake of plasma lipoprotein-derived cholesterol, events connected with the intracellular cholesterol processing and the role of crucial proteins that mediate cholesterol transport to mitochondria for its utilization for steroid hormone production. In particular, we discuss the structure and function of SR-BI, the importance of the selective cholesterol transport pathway in providing cholesterol substrate for steroid biosynthesis and the role of two key proteins, StAR and PBR/TSO in facilitating cholesterol delivery to inner mitochondrial membrane sites, where P450scc (CYP11A) is localized and where the conversion of cholesterol to pregnenolone (the common steroid precursor) takes place.

Effects of monosodium-L-glutamate administration on serum levels of reproductive hormones and cholesterol, epididymal sperm reserves and testicular histomorphology of male albino rats

“…This lowered serum cholesterol is believed to be partly responsible for the significantly lower serum testosterone recorded for the MSG-treated rats, as testosterone is one of the steroid hormones synthesised from cholesterol (Stocco, 1998;Hu et al, 2010). The significantly lower serum cholesterol recorded for rats given MSG in this study is in agreement with the report of Bazzano et al (1970) on humans and gerbils, but contrasts with the reports of Ahluwalia and Malik (1989) and Inyang et al (2012).…”

“…The significantly lower serum LH reported in this study is in agreement with the findings of Gong et al (1995). As cholesterol is known to be a precursor of steroid hormones (Stocco, 1998;Hu et al, 2010), it is thought that the significantly lower serum testosterone levels recorded for the rats treated with MSG in this study may be partly due to the lowered serum cholesterol levels. The significantly lower serum testosterone may also be partly attributed to a disruption in the hypothalamic-pituitarytestis regulatory axis (Nemeroff et al, 1981;Bodnár et al, 2001) mediated by the significantly lower serum levels of GnRH and LH recorded in the study.…”

Assessment of Molybdenum Induced Alteration in Oxidative Indices, Biochemical Parameters and Sperm Quality in Testis of Wistar Male Rats

“…Testicular cells have a dual requirement for cholesterol: they need cholesterol for membrane biogenesis and cell signaling as well as precursor required for androgen synthesis (Hu et al, 2010). Increased cholesterol content in testis of treated rats might be due to inhibition of testosterone biosynthesis as observed in the present study.…”

The Role of Mitochondria in Syncytiotrophoblast Cells: Bioenergetics and Steroidogenesis

“…LDLs are released from their endosomal receptors to make late endosomes/lysosomes and obtain free cholesterol as substrate for P450scc (Hu et al, 2010).…”