Adrenal cholesterol uptake from plasma lipoproteins: regulation by corticotropin.

Abstract

The transfer of lipoprotein-bound cholesterol into adrenal cells was examined. Adrenal glands from unstimulated or corticotropin stimulated hypophysectomized rats were incubated with high density lipoprotein (HDL) or low density lipoprotein LDL containing radiolabeled cholesterol. The rate of transfer of labeled cholesterol from HDL into the glands was two to three times greater than from LDL. Corticotropin stimulation increased the transfer of cholesterol from HDL but not LDL. The effects of corticotropin were not dependent on subsequent cholesterol utilization for steroidogenesis. The process of cholesterol transfer from HDL was linear with time over 2 hr at 370 and greatly reduced at 40. In addition, the transfer process became saturated above an HDL cholesterol concentration of 900 sg/ml. About 25% of the labeled adrenal cholesterol arising from HDL was recovered within the mitochondria. The labeled cholesterol within isolated mitochondria could undergo mitochondrial conversion to pregnenolone. Finally, the delipidated HDL apolipoproteins, apoA-I and apoA-II, when added to incubations containing less than saturating concentrations of HDL, stimulated transfer of labeled cholesterol from HDL to adrenal cells. These studies suggest that rat adrenal tissue possesses an HDL specific hormonally-responsive mechanism for accumulating extracellular cholesterol and that apoA-I and apoA-II have a significant function in the uptake process.The mechanisms responsible for transferring cholesterol from plasma into cells are of particular interest because of their possible role in atherosclerotic disease. Adrenal tissue may serve as a useful model for studying these mechanisms because studies in man (1, 2) and the rat (3, 4) showed that 80% or more of the cholesterol substrate for adrenal steroidogenesis may come from plasma. However, little is known about the process by which extracellular cholesterol enters the adrenal cells. Dexter et al. (4) have observed that the uptake process is stimulated by corticotropin (adrenocorticotrophic hormone, ACTH), and furthermore that the stimulatory effect of ACTH persists even when utilization of accumulating cholesterol is blocked by specific inhibitors.Serum cholesterol is lipoprotein bound, predominantly by the high density lipoprotein (HDL) and low density lipoprotein (LDL) fractions. In the rat (5), 60% of the circulating cholesterol is found in HDL and 30% in LDL, while in man 30% and 60% are found in HDL and LDL, respectively (6). In order to better understand the uptake of cholesterol by adrenal cells as well as ACTH regulation of the uptake process, we have examined the ability of HDL and LDL to serve as substrate for transfer of cholesterol to the adrenal. The observations reported here suggest that HDL is the preferred substrate for adrenal cholesterol uptake, and that uptake from HDL is regulated by ACTH. Furthermore, these studies suggest that the HDL apoproteins, apoA-I and apoA-II, play a role in the cholesterol uptake process. Table legends. Incubations were p...

The influence of plasma on basal and ACTH-stimulated in vitro adrenocortical steroidogenesis

“…The influence of lipoproteins on steroidogenesis has also been investigated by previous workers, although the majority of studies have been performed from a non-endocrinological perspective with the primary interest being directed towards the biochemistry of cholesterol per se and its subsequent uptake and metabolism, rather than the modulation of glucocorticoid secretion and synthesis. These studies on lipoprotein metabolism have revealed that LDL-cholesterol is preferentially utilised in mice (Faust et al 1977) and human fetal cells , Carr et al 1980, Higashijima et al 1987, whilst HDL-cholesterol is the preferred substrate in rats (Gwynne et al 1976, Andersen & Dietschy 1978, Gwynne & Hess 1980. Studies using bovine adrenocortical cells have demonstrated variable results and few have directly compared the relative effects of HDL and LDL, although preincubation with either lipoprotein increased both basal and ACTH-stimulated steroidogenesis (Koper et al 1985).…”

Disruption of cholesterol homeostasis by plant sterols

“…Although the adrenal gland can synthesize cholesterol, the major source of cholesterol for steroidogenesis is circulating lipoproteins (8,9). Cholesterol is acquired from circulating HDL by selective uptake via the scavenger receptor class B type I (SR-BI), and from circulating LDL by endocytosis mediated by the LDL receptor (LDLR) (10,11).…”

Role of lipoproteins and de-novo cholesterol synthesis in progesterone production by cultured bovine luteal cells

“…Rat luteal and adrenal cells use highdensity lipoprotein (HDL) in preference to low-density lipoprotein (LDL) for the provision of cholesterol substrate (Gwynne, Mahaffee, Brewer & Ney, 1976;Andersen & Dietschy, 1978;Schuler et ai, 1981;Bruot, Wiest & Collins, 1982 (Winkel, Snyder, MacDonald & Simpson, 1980;Carr etai, 1980Carr etai, , 1981Tureck & Strauss, 1982). Incubation of these cells with HDL either has no effect or causes an actual decrease in steroid synthesis (Tureck & Strauss, 1982), perhaps due to promotion of cholesterol efflux (Wu & Baily, 1980 (Savion, Laherty, Cohen, Lui & Gospodarowicz, 1982).…”