Intramitochondrial Cholesterol Transfer in Steroidogenic Cells

Stocco, Douglas M.; StraussIII, Jerome F.

doi:10.1007/978-1-4615-5113-3_11

Cited by 3 publications

(11 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This initial reaction is the principal committed, regulated, and rate-limiting step in steroid biosynthesis. The rate limiting nature of this step is not determined by the activity of CYP11A1 (i.e., enzymatic conversion of cholesterol to pregnenolone), but rather delivery of cholesterol to the substrate site of CYP11A1 (translocation of cholesterol from outer to an inner mitochondrial [steroidogenic] pool readily accessible to CYP11A1) [53]. The tropic hormones, ACTH and gonadotropins (LH, FSH) acutely stimulate this process by facilitating the availability of cytosolic free cholesterol and its transport to and accumulation in the inner mitochondrial CYP11A1 sites.…”

Section: Hormonal Regulation Of Steroidogenesismentioning

confidence: 99%

“…When steroidogenic cells are stimu-lated with tropic hormones in the presence of protein synthesis inhibitors such as cycloheximide, cholesterol accumulates in the outer mitochondrial membrane and is not transferred to the inner mitochondrial membrane [54][55][56][57]. Therefore, it has been proposed that a labile protein is required for cholesterol delivery to the inner mitochondrial membrane microdomains containing CYP11A1 [26,53,59].…”

Section: Hormonal Regulation Of Steroidogenesismentioning

confidence: 99%

“…The second critical step is the delivery of the cholesterol substrate to inner mitochondrial membrane sites of CYP11A1 [53,56,57]. As noted above, this step is considered rate-limiting because hydrophobic cholesterol cannot rapidly diffuse through the aqueous intermembrane space of the mitochondria to support acute steroid synthesis and requires the participation of a de novo synthesized labile protein [61][62][63][64][65].…”

Section: Hormonal Regulation Of Steroidogenesismentioning

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%

See 4 more Smart Citations

Impact of Aging on Steroid Hormone Biosynthesis and Secretion

Zaidi¹

2013

TOLSJ

View full text Add to dashboard Cite

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.

show abstract

Section: Hormonal Regulation Of Steroidogenesismentioning

confidence: 99%

Section: Hormonal Regulation Of Steroidogenesismentioning

confidence: 99%

Section: Hormonal Regulation Of Steroidogenesismentioning

confidence: 99%

Section: Oxidative Stress and Age-related Decline In Steroidogenesismentioning

confidence: 99%

Section: Aging and Excessive Oxidative Stressmentioning

confidence: 99%

See 3 more Smart Citations

Impact of Aging on Steroid Hormone Biosynthesis and Secretion

Zaidi¹

2013

TOLSJ

View full text Add to dashboard Cite

show abstract

Stimulatory effect of luteinizing hormone, insulin-like growth factor-1, and epidermal growth factor on progesterone secretion and viability of cultured bubaline luteal cells

et al. 2014

View full text Add to dashboard Cite

Steroidogenic Acute Regulatory Protein Binds Cholesterol and Modulates Mitochondrial Membrane Sterol Domain Dynamics

Petrescu¹,

Gallegos²,

Okamura³

et al. 2001

Journal of Biological Chemistry

Self Cite

119

108

View full text Add to dashboard Cite

The steroidogenic acute regulatory protein (StAR) mediates the rate-limiting step of steroidogenesis, delivery of cholesterol to the inner mitochondrial membrane. However, the mechanism whereby cholesterol translocation is accomplished has not been resolved. Recombinant StAR proteins lacking the first N-terminal 62 amino acids comprising the mitochondrial-targeting sequence were used to determine if StAR binds cholesterol and alters mitochondrial membrane cholesterol domains to enhance sterol transfer. First, a fluorescent NBD-cholesterol binding assay revealed 2 sterol binding sites (K d values near 32 nM), whereas the inactive A218V N-62 StAR mutant had only a single binding site with 8-fold lower affinity. Second, NBD-cholesterol spectral shifts and fluorescence resonance energy transfer from StAR Trp residues to NBD-cholesterol showed (i) close molecular interaction between these molecules (R 2/3 ‫؍‬ 33 Å) and (ii) sensitized NBD-cholesterol emission from only one of the two sterol binding sites. Third, circular dichroism showed that cholesterol binding induced a change in StAR secondary structure. Fourth, a fluorescent sterol transfer assay that did not require separation of donor and acceptor mitochondrial membranes demonstrated that StAR enhanced mitochondrial sterol transfer as much as 100-fold and induced/increased the formation of rapidly transferable cholesterol domains in isolated mitochondrial membranes. StAR was 67-fold more effective in transferring cholesterol from mitochondria of steroidogenic MA-10 cells than from human fibroblast mitochondria. In contrast, sterol carrier protein-2 (SCP-2) was only 2.2-fold more effective in mediating sterol transfer from steroidogenic cell mitochondria. Taken together these data showed that StAR is a cholesterol-binding protein, preferentially enhances sterol transfer from steroidogenic cell mitochondria, and interacts with mitochondrial membranes to alter their sterol domain structure and dynamics.

show abstract

Intramitochondrial Cholesterol Transfer in Steroidogenic Cells

Cited by 3 publications

References 73 publications

Impact of Aging on Steroid Hormone Biosynthesis and Secretion

Impact of Aging on Steroid Hormone Biosynthesis and Secretion

Stimulatory effect of luteinizing hormone, insulin-like growth factor-1, and epidermal growth factor on progesterone secretion and viability of cultured bubaline luteal cells

Steroidogenic Acute Regulatory Protein Binds Cholesterol and Modulates Mitochondrial Membrane Sterol Domain Dynamics

Contact Info

Product

Resources

About