The Experts below are selected from a list of 111 Experts worldwide ranked by ideXlab platform
Douglas M Stocco - One of the best experts on this subject based on the ideXlab platform.
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the role of pbr tspo in steroid biosynthesis challenged
Endocrinology, 2014Co-Authors: Douglas M StoccoAbstract:The events that regulate the rapid synthesis of steroid Hormones in response to Trophic Hormone stimulation of the steroidogenic cells have been the ongoing subject of intense interest for several decades. Much of the early work performed in this area determined that the acute regulation of steroid Hormone biosynthesis required the rapid, de novo synthesis of a protein(s) whose function appeared to be involved in mediating the delivery of cholesterol, the substrate for all steroid Hormones, from the outer mitochondrial membrane to the inner mitochondrial membrane. The existence of a protein that was necessary for intramitochondrial transfer of cholesterol was first postulated by James Ferguson in 1963 (1). This transfer is an absolute requirement for steroid biosynthesis, because the cholesterol side-chain cleavage enzyme system that converts cholesterol to pregnenolone, the first steroid synthesized, resides on the inner side of the inner mitochondrial membrane. As such, the hydrophobic cholesterol substrate is unable to traverse the aqueous intermembrane space and reach the inner mitochondrial membrane through diffusion. The next 3 decades saw a focused interest in determining the identity of this putative regulator protein (2–13). These studies gave rise to a list of the characteristics that the putative protein regulator appeared to possess, including those described above. Later work introduced other putative regulator proteins, the sterol carrier protein 2 (14), the steroidogenesis activator polypeptide (15, 16), the peripheral benzodiazepine receptor (PBR) (17), and the steroidogenic acute regulatory protein (StAR) (18). Although space limitations do not allow for a critical evaluation of the characteristics of each of the candidates that have been put forth as the putative regulator protein over the years, these candidates have been described in an earlier review (19).
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multiple signaling pathways regulating steroidogenesis and steroidogenic acute regulatory protein expression more complicated than we thought
Molecular Endocrinology, 2005Co-Authors: Douglas M Stocco, Xingjia Wang, Youngah Jo, Pulak R MannaAbstract:Steroid Hormone biosynthesis in steroidogenic cells is regulated through Trophic Hormone activation of protein kinase A (PKA) signaling pathways. However, many examples of the regulation of steroid synthesis via pathways other than the PKA pathway have been documented. In some cases these pathways act independently of PKA activation whereas in other cases, they act synergistically with it. The current understanding of additional signaling pathways and factors, such as the protein kinase C pathway, arachidonic acid metabolites, growth factors, chloride ion, the calcium messenger system, and others capable of regulating/modulating steroid Hormone biosynthesis, and in many cases steroidogenic acute regulatory protein expression, are discussed in this review.
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targeted disruption of the mouse gene encoding steroidogenic acute regulatory protein provides insights into congenital lipoid adrenal hyperplasia
Proceedings of the National Academy of Sciences of the United States of America, 1997Co-Authors: Kathleen M Caron, Douglas M Stocco, Barbara J. Clark, Shiu Ching Soo, William C Wetsel, Keith L ParkerAbstract:An essential component of regulated steroidogenesis is the translocation of cholesterol from the cytoplasm to the inner mitochondrial membrane where the cholesterol side-chain cleavage enzyme carries out the first committed step in steroidogenesis. Recent studies showed that a 30-kDa mitochondrial phosphoprotein, designated steroidogenic acute regulatory protein (StAR), is essential for this translocation. To allow us to explore the roles of StAR in a system amenable to experimental manipulation and to develop an animal model for the human disorder lipoid congenital adrenal hyperplasia (lipoid CAH), we used targeted gene disruption to produce StAR knockout mice. These StAR knockout mice were indistinguishable initially from wild-type littermates, except that males and females had female external genitalia. After birth, they failed to grow normally and died from adrenocortical insufficiency. Hormone assays confirmed severe defects in adrenal steroids—with loss of negative feedback regulation at hypothalamic–pituitary levels—whereas Hormones constituting the gonadal axis did not differ significantly from levels in wild-type littermates. Histologically, the adrenal cortex of StAR knockout mice contained florid lipid deposits, with lesser deposits in the steroidogenic compartment of the testis and none in the ovary. The sex-specific differences in gonadal involvement support a two-stage model of the pathogenesis of StAR deficiency, with Trophic Hormone stimulation inducing progressive accumulation of lipids within the steroidogenic cells and ultimately causing their death. These StAR knockout mice provide a useful model system in which to determine the mechanisms of StAR’s essential roles in adrenocortical and gonadal steroidogenesis.
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the purification cloning and expression of a novel luteinizing Hormone induced mitochondrial protein in ma 10 mouse leydig tumor cells characterization of the steroidogenic acute regulatory protein star
Journal of Biological Chemistry, 1994Co-Authors: Barbara J. Clark, Steven R King, J Wells, Douglas M StoccoAbstract:Abstract The acute response of steroidogenic cells to Trophic Hormone stimulation is the mobilization of cholesterol from cellular stores to the mitochondrial outer membrane and the transfer of this cholesterol to the mitochondrial inner membrane where the first enzymatic step in steroidogenesis occurs. The transfer of cholesterol across the mitochondrial membranes is dependent upon de novo protein synthesis, and this is the regulated step in the process. Although the newly synthesized regulatory protein(s) have yet to be identified, we previously have proposed a candidate protein which we identified in MA-10 cells that is synthesized in response to luteinizing Hormone stimulation and that is localized to the mitochondria. In the present study, we report the isolation of a cDNA that encodes this luteinizing Hormone-induced protein. Analysis of the cDNA and protein sequences reveals this is a novel protein. Importantly, we demonstrate for the first time that expression of the protein in MA-10 cells in the absence of Hormone stimulation is sufficient to induce steroid production. We conclude that this protein is required in the acute regulation of steroidogenesis and propose to call this protein the Steroidogenic Acute Regulatory protein (StAR).
Arnold M Moses - One of the best experts on this subject based on the ideXlab platform.
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multiple endocrine organ refractoriness to Trophic Hormone stimulation
Annals of Internal Medicine, 2020Co-Authors: Stephen J Gordon, Arnold M MosesAbstract:Excerpt Pituitary tumors are usually nonfunctioning, the associated loss of end organ function being due to diminished Trophic Hormone secretion. It has been noted, however, that single primary end...
Keith L Parker - One of the best experts on this subject based on the ideXlab platform.
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targeted disruption of the mouse gene encoding steroidogenic acute regulatory protein provides insights into congenital lipoid adrenal hyperplasia
Proceedings of the National Academy of Sciences of the United States of America, 1997Co-Authors: Kathleen M Caron, Douglas M Stocco, Barbara J. Clark, Shiu Ching Soo, William C Wetsel, Keith L ParkerAbstract:An essential component of regulated steroidogenesis is the translocation of cholesterol from the cytoplasm to the inner mitochondrial membrane where the cholesterol side-chain cleavage enzyme carries out the first committed step in steroidogenesis. Recent studies showed that a 30-kDa mitochondrial phosphoprotein, designated steroidogenic acute regulatory protein (StAR), is essential for this translocation. To allow us to explore the roles of StAR in a system amenable to experimental manipulation and to develop an animal model for the human disorder lipoid congenital adrenal hyperplasia (lipoid CAH), we used targeted gene disruption to produce StAR knockout mice. These StAR knockout mice were indistinguishable initially from wild-type littermates, except that males and females had female external genitalia. After birth, they failed to grow normally and died from adrenocortical insufficiency. Hormone assays confirmed severe defects in adrenal steroids—with loss of negative feedback regulation at hypothalamic–pituitary levels—whereas Hormones constituting the gonadal axis did not differ significantly from levels in wild-type littermates. Histologically, the adrenal cortex of StAR knockout mice contained florid lipid deposits, with lesser deposits in the steroidogenic compartment of the testis and none in the ovary. The sex-specific differences in gonadal involvement support a two-stage model of the pathogenesis of StAR deficiency, with Trophic Hormone stimulation inducing progressive accumulation of lipids within the steroidogenic cells and ultimately causing their death. These StAR knockout mice provide a useful model system in which to determine the mechanisms of StAR’s essential roles in adrenocortical and gonadal steroidogenesis.
Pulak R Manna - One of the best experts on this subject based on the ideXlab platform.
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multiple signaling pathways regulating steroidogenesis and steroidogenic acute regulatory protein expression more complicated than we thought
Molecular Endocrinology, 2005Co-Authors: Douglas M Stocco, Xingjia Wang, Youngah Jo, Pulak R MannaAbstract:Steroid Hormone biosynthesis in steroidogenic cells is regulated through Trophic Hormone activation of protein kinase A (PKA) signaling pathways. However, many examples of the regulation of steroid synthesis via pathways other than the PKA pathway have been documented. In some cases these pathways act independently of PKA activation whereas in other cases, they act synergistically with it. The current understanding of additional signaling pathways and factors, such as the protein kinase C pathway, arachidonic acid metabolites, growth factors, chloride ion, the calcium messenger system, and others capable of regulating/modulating steroid Hormone biosynthesis, and in many cases steroidogenic acute regulatory protein expression, are discussed in this review.
Barbara J. Clark - One of the best experts on this subject based on the ideXlab platform.
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targeted disruption of the mouse gene encoding steroidogenic acute regulatory protein provides insights into congenital lipoid adrenal hyperplasia
Proceedings of the National Academy of Sciences of the United States of America, 1997Co-Authors: Kathleen M Caron, Douglas M Stocco, Barbara J. Clark, Shiu Ching Soo, William C Wetsel, Keith L ParkerAbstract:An essential component of regulated steroidogenesis is the translocation of cholesterol from the cytoplasm to the inner mitochondrial membrane where the cholesterol side-chain cleavage enzyme carries out the first committed step in steroidogenesis. Recent studies showed that a 30-kDa mitochondrial phosphoprotein, designated steroidogenic acute regulatory protein (StAR), is essential for this translocation. To allow us to explore the roles of StAR in a system amenable to experimental manipulation and to develop an animal model for the human disorder lipoid congenital adrenal hyperplasia (lipoid CAH), we used targeted gene disruption to produce StAR knockout mice. These StAR knockout mice were indistinguishable initially from wild-type littermates, except that males and females had female external genitalia. After birth, they failed to grow normally and died from adrenocortical insufficiency. Hormone assays confirmed severe defects in adrenal steroids—with loss of negative feedback regulation at hypothalamic–pituitary levels—whereas Hormones constituting the gonadal axis did not differ significantly from levels in wild-type littermates. Histologically, the adrenal cortex of StAR knockout mice contained florid lipid deposits, with lesser deposits in the steroidogenic compartment of the testis and none in the ovary. The sex-specific differences in gonadal involvement support a two-stage model of the pathogenesis of StAR deficiency, with Trophic Hormone stimulation inducing progressive accumulation of lipids within the steroidogenic cells and ultimately causing their death. These StAR knockout mice provide a useful model system in which to determine the mechanisms of StAR’s essential roles in adrenocortical and gonadal steroidogenesis.
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the purification cloning and expression of a novel luteinizing Hormone induced mitochondrial protein in ma 10 mouse leydig tumor cells characterization of the steroidogenic acute regulatory protein star
Journal of Biological Chemistry, 1994Co-Authors: Barbara J. Clark, Steven R King, J Wells, Douglas M StoccoAbstract:Abstract The acute response of steroidogenic cells to Trophic Hormone stimulation is the mobilization of cholesterol from cellular stores to the mitochondrial outer membrane and the transfer of this cholesterol to the mitochondrial inner membrane where the first enzymatic step in steroidogenesis occurs. The transfer of cholesterol across the mitochondrial membranes is dependent upon de novo protein synthesis, and this is the regulated step in the process. Although the newly synthesized regulatory protein(s) have yet to be identified, we previously have proposed a candidate protein which we identified in MA-10 cells that is synthesized in response to luteinizing Hormone stimulation and that is localized to the mitochondria. In the present study, we report the isolation of a cDNA that encodes this luteinizing Hormone-induced protein. Analysis of the cDNA and protein sequences reveals this is a novel protein. Importantly, we demonstrate for the first time that expression of the protein in MA-10 cells in the absence of Hormone stimulation is sufficient to induce steroid production. We conclude that this protein is required in the acute regulation of steroidogenesis and propose to call this protein the Steroidogenic Acute Regulatory protein (StAR).
