Steroidogenic tissues

Mitochondrial cytochrome P450 systems are found in steroidogenic tissues such as adrenal cortex, testis, ovary, and placenta and are concerned with the biosyn-... 

HDL Picks up cholesterol accumulating in blood vessels Delivers cholesterol to liver and steroidogenic tissues via scavenger receptor (SR-BI) Shuttles apoC-II and apoE in blood apoA-1 Activates lecithin cholesterol acylwansferase (LCAT) to produce cholesterol esters... 

HDL cholesterol picked up in the periphery can also enter cells through a scavenger receptor, SR-Bl. This receptor is expressed at high levels in hepatocytes and the steroidogenic tissues, including ovaries, testes, and areas of the adrenal glands. This receptor does not mediate endo-cytosis of the HDL, but rather transfer of cholesterol into the cell by a mechanism not yet clearly defined. This process is shown in Figure 1-15-7. 

Many steroidogenic tissues synthesize steroid hormones from the cholesterol provided by LDL particles. 

HDL particles extract cholesterol from peripheral membranes and, after esterification of cholesterol to a fatty acid, the cholesteryl esters are delivered to the liver (to make bile salts) or steroidogenic tissues (precursor of steroids). 

Cholesterol is transported into the mitochondria of steroidogenic tissue, where side chain cleavage is carried out. In common with other mixed-function oxidase systems, the cholesterol side chain cleavage requires reduced nicotinamide-adenine dinucleotide phosphate... 

HDL may be taken up in the liver by receptor-mediated endocytosis, but at least some of the cholesterol in HDL is delivered to other tissues by a novel mechanism. HDL can bind to plasma membrane receptor proteins called SR-BI in hepatic and steroidogenic tissues such as the adrenal gland. These receptors mediate not endocytosis but a partial and selective transfer of cholesterol and other lipids in HDL into the cell. Depleted HDL then dissociates to recirculate in the bloodstream and extract more lipids from chylomicron and VLDL remnants. Depleted HDL can also pick up cholesterol stored in extrahepatic tissues and carry it to the liver, in reverse cholesterol transport pathways (Fig. 21-40). In one reverse transport path, interaction of nascent HDL with SR-BI receptors in cholesterol-rich cells triggers passive movement of cholesterol from the cell surface into HDL, which then carries it back to the liver. In a second pathway, apoA-I in depleted HDL in-... 

Little is known about apoA-I catabolism or even HDL catabolism. In the rat, HDL can deliver cholesterol to steroidogenic tissues although this is thought to be receptor mediated, the mechanism of such binding is not clear (A20, C12, G37, K27). High-affinity specific binding sites for HDL (and LDL) have been demonstrated in rat liver cells (C9, 09, V2) and in rat intestinal mucosal cells (S63). 

Although cholesterol is accepted as the major precursor of steroid hormones as a result of side-chain cleavage to pregnenolone (see below), research over the past decade or so has focused on the mechanisms by which steroidogenic tissues obtain cholesterol. It should be borne in mind that such tissues require cholesterol, not only for steroid synthesis but also for membrane synthesis, and hence require more of the precursor sterol than other tissues. Morris and Chaikoff [1] showed that the bulk of rat adrenal cholesterol was derived from circulating cholesterol, and later work revealed a similar state of affairs in humans. 

Cholesterol appears to be taken up from plasma lipoproteins by steroidogenic tissues by two receptor-mediated pathways - the LDL pathway and the HDL pathway. Not all tissues of all species can utilise both of these thus, the LDL pathway appears to occur in all species, including man, whereas the HDL pathway occurs mainly in rodents. LDL lipoproteins interact specifically with cell surface-bound receptors, as shown for, e.g., adrenal [9] and ovary [10], after which internalization occurs by endocytosis and hydrolysis of LDLs, plus their cholesterol ester complement by lysosomal action. 

Once cholesterol is transferred to the inner mitochondrial membrane of steroidogenic tissues such as adrenals, ovaries and testes, it encounters the enzyme system known as the cholesterol SCC system. This probably comprises 20- and 22-hydroxylases and a C-20,22-lyase, all tightly bound to the inner face of the membrane and associated with a specific cytochrome />-450scc. In addition, molecular 02 is necessary together with NADPH reductase and non-haem iron sulphur protein, which are called adrenodoxin reductase and adrenodoxin, respectively, in the adrenal [24] (Fig. 3). 

The structure and properties of this enzyme have been reviewed thoroughly by Talalay and his co-workers (42). Isomerase activities have been observed in all mammalian steroidogenic tissues. However, these mammalian isomerases have been difficult to study due to their mem-... 

ABCA1 mediates the first step in the energy-dependent efflux of cholesterol from the cell to form HDL for reverse cholesterol transport (Fig. 15-2). While all tissues in the body can synthesize cholesterol, only the liver and steroidogenic tissues can metabolize it. Surplus cholesterol in cells of the peripheral tissues is transported to the liver for either redistribution to other cells or for excretion either as free cholesterol or as a bile salt after conversion in the liver. Therefore, this reverse cholesterol transport system plays a pivotal role in cholesterol homeostasis with HDL as one of the key players. 

The ABCA1 gene has been localized to 9q31on the long arm of chromosome 9- It spans 149 kb and has 50 exons. The first intron has been shown to act as an alternative promoter. ABCA1 is ubiquitously expressed, with notable expression in liver, brain, and steroidogenic tissues. Furthermore, it is expressed in confluent but... 

Brain Olfactory Intestinal Tract Steroidogenic Tissues... 

HDL, like LDL, is a cholesterol-rich particle, and is distinct from the other lipoprotein classes in that it does not contain apoB. HDL levels are inversely correlated with risk for atherosclerosis (Wilson et al., 1988). Nascent HDL particles are produced by direct synthesis (Hamilton, 1984), and excess surface remnants from chylomicrons and VLDL produced during the action of lipoprotein lipase (as noted above) enter the HDL density class. HDL appears to be involved in delivery of cholesterol to steroidogenic tissues as well as the removal of excess cholesterol from peripheral tissues and excretion from the system. This HDL-mediated removal of cholesterol has been termed reverse cholesterol transport (Glomset, 1968). Although apolipoproteins present in HDLs are cleared by the liver, the reverse cholesterol transport pathway has never been directly demonstrated. HDL can remove cholesterol from tissues, a process that may be partially mediated by interaction with a putative HDL receptor, with apoA-I as the ligand for that receptor (Oram el ai, 1983). The existence of an HDL receptor remains controversial saturable HDL binding may not be mediated by a specific apolipoprotein ligand and may not even be required for transfer of cholesterol from cells to... 

Cholesterol can be synthesized in almost all cells, but the liver, intestine, and the steroidogenic tissues such as the adrenal glands and reproductive tissues are the primary sites. 

Steroidogenesis is a highly regulated biological process that is required for physiological homeostasis. This process takes place in specialized steroidogenic tissues where the biosynthesis of steroid hormones occurs in a highly... 

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