Scavenger receptor class BI and selective cholesteryl ester uptake: partners in the regulation of steroidogenesis

Azhar, Salman; Reaven, Eve

doi:10.1016/s0303-7207(02)00222-8

Cited by 173 publications

(153 citation statements)

References 277 publications

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“…SR-BI-mediated internalization of apoA-I from HDL has been shown in both murine and human hepatocytes (33) and Madin-Darby canine kidney cells (34). However, little if any SR-BI-mediated uptake of HDL particles or apolipoproteins is observed in CHO cells (25,26) or steroidogenic cells (25,35), in which SR-BI levels and rates of HDL-selective uptake are high. In such cells, therefore, selective uptake does not appear to depend on internalization.…”

Section: Discussionmentioning

confidence: 99%

Serum Amyloid A Is a Ligand for Scavenger Receptor Class B Type I and Inhibits High Density Lipoprotein Binding and Selective Lipid Uptake

Cai

Beer

et al. 2005

Journal of Biological Chemistry

159

141

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Serum amyloid A is an acute phase protein that is carried in the plasma largely as an apolipoprotein of high density lipoprotein (HDL). In this study we investigated whether SAA is a ligand for the HDL receptor, scavenger receptor class B type I (SR-BI), and how SAA may influence SR-BI-mediated HDL binding and selective cholesteryl ester uptake. Studies using Chinese hamster ovary cells expressing SR-BI showed that 125 Ilabeled SAA, both in lipid-free form and in reconstituted HDL particles, functions as a high affinity ligand for SR-BI. SAA also bound with high affinity to the hepatocyte cell line, HepG2. Alexa-labeled SAA was shown by fluorescence confocal microscopy to be internalized by cells in a SR-BI-dependent manner. To assess how SAA association with HDL influences HDL interaction with SR-BI, SAA-containing HDL was isolated from mice overexpressing SAA through adenoviral gene transfer. SAA presence on HDL had little effect on HDL binding to SR-BI but decreased (30 -50%) selective cholesteryl ester uptake. Lipid-free SAA, unlike lipid-free apoA-I, was an effective inhibitor of both SR-BI-dependent binding and selective cholesteryl ester uptake of HDL. We have concluded that SR-BI plays a key role in SAA metabolism through its ability to interact with and internalize SAA and, further, that SAA influences HDL cholesterol metabolism through its inhibitory effects on SR-BI-mediated selective lipid uptake.

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Section: Discussionmentioning

confidence: 99%

Serum Amyloid A Is a Ligand for Scavenger Receptor Class B Type I and Inhibits High Density Lipoprotein Binding and Selective Lipid Uptake

Cai

Beer

et al. 2005

Journal of Biological Chemistry

159

141

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“…Cholesterol can be obtained from three principal sources: a) cholesterol synthesized de novo from the acetate; b) cholesterol derived from the circulating lipoproteins; and c) cholesterol recruited by the hydrolysis of cytoplasmic cholesteryl esters stored in the form of lipid droplets (Fig. 2) [25,26]. In some cultured cells including steroidogenic cells, cholesterol can also be obtained from the plasma membrane [27][28][29].…”

Section: Substratementioning

confidence: 99%

“…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].…”

Section: Cholesterol Requirement Of Testicular Leydig Cellmentioning

confidence: 99%

“…Work over the years from this laboratory has shown that the basic problem, at least in aging rats, is that adequate amounts of cholesterol are not available to adrenal (adrenocortical cells) and testis (Leydig cells) for the first step in steroid biosynthesis (i.e., conversion of cholesterol to pregnenolone by the inner mitochondrial membrane-associated side-chain cleavage enzyme system, P450 scc [also designated as CYP11A1]) [25,53,58,66,76,90]. Questions now center on the nature of this defect.…”

Section: Oxidative Stress and Age-related Decline In Steroidogenesismentioning

confidence: 99%

“…Because lipid peroxidation involving membranes could affect membrane composition, structure, fluidity and function (e.g. the activation of membrane proteins like receptors, ion channels, participants of signal transduction pathways, transport proteins and membrane associated enzymes [362][363][364][365][366]), and virtually every event associated with cholesterol processing and steroidogenesis is dependent on the integrity of cell membranes [1][2][3][4][5][6]25,26,53,81,90,[367][368][369], the likelihood of steroidogenesis being adversely affected is quite high. As a result, steroidogenic cells, like other mammalian cells, are well equipped with antioxidant systems to combat free radicals [370][371][372][373][374][375].…”

Section: Aging and Excessive Oxidative Stressmentioning

confidence: 99%

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Impact of Aging on Steroid Hormone Biosynthesis and Secretion

Zaidi¹

2013

TOLSJ

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Steroid hormones are lipophilic, low-molecular weight organic compounds all of which are derived from cholesterol. They are primarily synthesized by steroidogenic glands such as gonads (ovary and testis), the adrenal gland and, during pregnancy, by the placental trophoblasts. Limited steroid synthesis also takes place in the brain. Steroid hormones are crucial for the proper functioning of the body. They mediate a wide variety of vital physiological functions, ranging from maintaining normal reproductive function and secondary sexual characteristics, to regulating virtually every metabolic process in the body. Like many age-related endocrine disorders, aging also progressively impacts the tissue-specific synthesis and secretion of steroid hormones. The goal of this review is to summarize the effects of aging on steroid hormone synthesis and secretion by the adrenal gland and gonads of both human and experimental animal models, to describe the potential involvement of excessive oxidative stress in mediating age-related alterations in steroidogenesis, and to discuss the possible underlying mechanisms involved.

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Steroidogenesis—Adrenal Cell Signal Transduction

Gallo‐Payet

Battista

2014

Comprehensive Physiology

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The purpose of this article is to review fundamentals in adrenal gland histophysiology. Key findings regarding the important signaling pathways involved in the regulation of steroidogenesis and adrenal growth are summarized. We illustrate how adrenal gland morphology and function are deeply interconnected in which novel signaling pathways (Wnt, Sonic hedgehog, Notch, β-catenin) or ionic channels are required for their integrity. Emphasis is given to exploring the mechanisms and challenges underlying the regulation of proliferation, growth, and functionality. Also addressed is the fact that while it is now well-accepted that steroidogenesis results from an enzymatic shuttle between mitochondria and endoplasmic reticulum, key questions still remain on the various aspects related to cellular uptake and delivery of free cholesterol. The significant progress achieved over the past decade regarding the precise molecular mechanisms by which the two main regulators of adrenal cortex, adrenocorticotropin hormone (ACTH) and angiotensin II act on their receptors is reviewed, including structure-activity relationships and their potential applications. Particular attention has been given to crucial second messengers and how various kinases, phosphatases, and cytoskeleton-associated proteins interact to ensure homeostasis and/or meet physiological demands. References to animal studies are also made in an attempt to unravel associated clinical conditions. Many of the aspects addressed in this article still represent a challenge for future studies, their outcome aimed at providing evidence that the adrenal gland, through its steroid hormones, occupies a central position in many situations where homeostasis is disrupted, thus highlighting the relevance of exploring and understanding how this key organ is regulated. © 2014 American Physiological Society. Compr Physiol 4:889-964, 2014.

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Scavenger receptor class BI and selective cholesteryl ester uptake: partners in the regulation of steroidogenesis

Cited by 173 publications

References 277 publications

Serum Amyloid A Is a Ligand for Scavenger Receptor Class B Type I and Inhibits High Density Lipoprotein Binding and Selective Lipid Uptake

Serum Amyloid A Is a Ligand for Scavenger Receptor Class B Type I and Inhibits High Density Lipoprotein Binding and Selective Lipid Uptake

Impact of Aging on Steroid Hormone Biosynthesis and Secretion

Steroidogenesis—Adrenal Cell Signal Transduction

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