Cholesterol uptake in adrenal and gonadal tissues the SR BI and selective pathway connection

Abstract

A constant supply of cholesterol is needed as a substrate for steroid hormone synthesis in steroidogenic tissues. Although there are three potential sources, which could contribute to the 'cholesterol pool', needed for steroidogenesis (i.e., de novo synthesis, hydrolysis of stored cholesteryl esters and exogenous lipoproteins), current evidence suggests that plasma lipoproteins are the major source of cholesterol for steroid production in adrenal gland, ovary and, under certain conditions, testicular Leydig cells. In many species, steroid producing cells and tissues obtain this lipoprotein-cholesterol by a unique pathway in which circulating lipoproteins bind to the surface of the steroidogenic cells and contribute their cholesteryl esters to the cells by a 'selective' process. This is a process in which cholesterol is selectively absorbed while the lipoprotein remains at the cell surface. The discovery of a specific receptor for this process (scavenger receptor class B, type I, known as SR-BI) has revolutionized our knowledge about the selective uptake pathway. The present review summarizes the functional importance of the selective pathway as a bulk cholesterol delivery system for steroidogenesis, and attempts to detail the expression, regulation and characteristics of SR-BI as it is deployed in steroidogenic systems as a means of achieving cholesterol balance.

Prediabetic and diabetic in vivo modification of circulating low-density lipoprotein attenuates its stimulatory effect on adrenal aldosterone and cortisol secretion

“…Cholesterol can be derived from the uptake of cholesterol-rich lipoproteins, as well as from endogenous cholesterol synthesis and by the mobilization of stored cholesteryl esters (Azhar et al 2003). Accumulating evidence suggests that plasma lipoproteins, namely LDL and HDL, are the major sources of cholesterol for steroid production in the adrenal gland.…”

Impact of Aging on Steroid Hormone Biosynthesis and Secretion

“…The uptake of HDL cholesterol by steroidogenic cells, however, involves a unique pathway, termed 'selective' pathway in which cholesteryl esters (CEs) are selectively transferred to the cell interior without the parallel uptake and degradation of the HDL particle itself (Fig. 2) [33,34]. SR-BI, a multiligand cell surface receptor, binds HDL with high affinity and mediates selective cholesterol uptake [33,34].…”

“…2) [33,34]. SR-BI, a multiligand cell surface receptor, binds HDL with high affinity and mediates selective cholesterol uptake [33,34]. The selectively delivered CEs are either hydrolyzed by the neutral cholesteryl ester hydrolase (CEH) and released as cholesterol used for steroiodogenesis, or stored in cellular lipid droplets [33,35].…”

“…For example, in the rodent (rat) Leydig cells, the cholesterol that is synthesized de novo within the cell is the most important source of testosterone synthesis [36][37][38][39], but in the human testis, both endogenously synthesized cholesterol as well as LDL-derived cholesterol contribute to testosterone production [39,40]. As noted above, all steroidogenic cells, however, contain the intracellular cholesterol pool in the form of cholesterol esters (lipid droplets) which are regarded as a short-term store of substrates that enables cells to respond rapidly to trophic hormone stimulation [25,33,39].…”

Hormonal and Neural Mechanisms Regulating Hormone Steroids Secretion

“…Depending on the cell, the synthesis of lipoprotein receptors is stimulated by the adreno-corticotropin-hormone (ACTH) and luteinizing hormone (LH). The source of cholesterol for steroidogenesis varies according to the animal studied (Azhar et al, 2003;Hu et al, 2011). SR-BI synthesis in adrenal cells is stimulated by ACTH and inhibited by glucocorticoids (Mavridou et al, 2010).…”