Modulation of peripheral benzodiazepine receptors in female rat genital organs by various gonadal steroids

Bar‐Ami, Shalom; Amiri, Zamir; Fares, Fuad; Gavish, Moshe

doi:10.1016/0024-3205(94)90131-7

Cited by 11 publications

(5 citation statements)

References 44 publications

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“…This release of intracellular stores of Ca 2+ is mediated by membrane ERα transactivating the mGluR1a and the generation of IP 3 (12). It had not been clear how this fit with the observed E 2 regulation of levels of TSPO ligand binding and TSPO mRNA (39–42). Moreover, an analysis of the amino acid sequence of the rat TSPO gene revealed the presence of several putative phosphorylation sites (43).…”

Section: Discussionmentioning

confidence: 98%

Estradiol Modulates Translocator Protein (TSPO) and Steroid Acute Regulatory Protein (StAR) via Protein Kinase A (PKA) Signaling in Hypothalamic Astrocytes

et al. 2014

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The ability of the central nervous system to synthesize steroid hormones has wide-ranging implications for physiology and pathology. Among the proposed roles of neurosteroids is the regulation of the LH surge. This involvement in the estrogen-positive feedback demonstrates the integration of peripheral steroids with neurosteroids. Within the female hypothalamus, estradiol from developing follicles stimulates progesterone synthesis in astrocytes, which activate neural circuits regulating gonadotropin (GnRH) neurons. Estradiol acts at membrane estrogen receptor-α to activate cellular signaling that results in the release of inositol trisphosphate-sensitive calcium stores that are sufficient to induce neuroprogesterone synthesis. The purpose of the present studies was to characterize the estradiol-induced signaling leading to activation of steroid acute regulatory protein (StAR) and transporter protein (TSPO), which mediate the rate-limiting step in steroidogenesis, ie, the transport of cholesterol into the mitochondrion. Treatment of primary cultures of adult female rat hypothalamic astrocytes with estradiol induced a cascade of phosphorylation that resulted in the activation of a calcium-dependent adenylyl cyclase, AC1, elevation of cAMP, and activation of both StAR and TSPO. Blocking protein kinase A activation with H-89 abrogated the estradiol-induced neuroprogesterone synthesis. Thus, together with previous results, these experiments completed the characterization of how estradiol action at the membrane leads to the augmentation of neuroprogesterone synthesis through increasing cAMP, activation of protein kinase A, and the phosphorylation of TSPO and StAR in hypothalamic astrocytes.

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Section: Discussionmentioning

confidence: 98%

Estradiol Modulates Translocator Protein (TSPO) and Steroid Acute Regulatory Protein (StAR) via Protein Kinase A (PKA) Signaling in Hypothalamic Astrocytes

et al. 2014

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“…Several studies have described that exposure to steroid hormones modifies TSPO levels, determined through TSPO binding studies (56)(57)(58). mRNA and protein levels do not always correlate, however, and the protein is reported to undergo conformational changes that result in increased ligand binding (55,59).…”

Section: Steroidogenic Nih-3t3 Cells (42)mentioning

confidence: 99%

TSPO: kaleidoscopic 18-kDa amid biochemical pharmacology, control and targeting of mitochondria

Gatliff

Campanella

2016

Biochemical Journal

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The 18-kDa translocator protein (TSPO) localizes in the outer mitochondrial membrane (OMM) of cells and is readily up-regulated under various pathological conditions such as cancer, inflammation, mechanical lesions and neurological diseases. Able to bind with high affinity synthetic and endogenous ligands, its core biochemical function resides in the translocation of cholesterol into the mitochondria influencing the subsequent steps of (neuro-)steroid synthesis and systemic endocrine regulation. Over the years, however, TSPO has also been linked to core cellular processes such as apoptosis and autophagy. It interacts and forms complexes with other mitochondrial proteins such as the voltage-dependent anion channel (VDAC) via which signalling and regulatory transduction of these core cellular events may be influenced. Despite nearly 40 years of study, the precise functional role of TSPO beyond cholesterol trafficking remains elusive even though the recent breakthroughs on its high-resolution crystal structure and contribution to quality-control signalling of mitochondria. All this along with a captivating pharmacological profile provides novel opportunities to investigate and understand the significance of this highly conserved protein as well as contribute the development of specific therapeutics as presented and discussed in the present review.

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“…Steroid hormone changes during the rat oestrous cycle affect TSPO levels in various genital organs (Fares et al, 1988), and ovarian and synthetic steroids significantly increase TSPO levels in the ovary, oviduct, and uterus (Bar-Ami et al, 1994). Thus, estradiol is likely a tissue-specific regulator of TSPO expression (Bar-Ami et al, 1994; Bitran et al, 1998; Fares et al, 1988; Gavish et al, 1986; Mazurika et al, 2009; Veenman and Gavish, 2006; Weizman et al, 1997). …”

Section: -Regulation Of Tspo Expression By Hormones Chemicals and mentioning

confidence: 99%

Regulation of translocator protein 18kDa (TSPO) expression in health and disease states☆

Batarseh

Papadopoulos

2010

Molecular and Cellular Endocrinology

237

236

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Translocator protein (TSPO) is an 18-kDa high affinity cholesterol- and drug-binding protein found primarily in the outer mitochondrial membrane. Although TSPO is found in many tissue types, it is expressed at the highest levels under normal conditions in tissues that synthesize steroids. TSPO has been associated with cholesterol import into mitochondria, a key function in steroidogenesis, and directly or indirectly with multiple other cellular functions including apoptosis, cell proliferation, differentiation, anion transport, porphyrin transport, heme synthesis, and regulation of mitochondrial function. Aberrant expression of TSPO has been linked to multiple diseases, including cancer, brain injury, neurodegeneration, and ischemia reperfusion injury. There has been an effort during the last decade to understand the mechanisms regulating tissue- and disease-specific TSPO expression and to identify pharmacological means to control its expression. This review focuses on the current knowledge regarding the chemicals, hormones, and molecular mechanisms regulating Tspo gene expression under physiological conditions in a tissue- and disease-specific manner. The results described here provide evidence that the PKCε-ERK1/2-AP1/Stat3 signal transduction pathway is the primary regulator of Tspo gene expression in normal and pathological tissues expressing high levels of TSPO.

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Modulation of peripheral benzodiazepine receptors in female rat genital organs by various gonadal steroids

Cited by 11 publications

References 44 publications

Estradiol Modulates Translocator Protein (TSPO) and Steroid Acute Regulatory Protein (StAR) via Protein Kinase A (PKA) Signaling in Hypothalamic Astrocytes

Estradiol Modulates Translocator Protein (TSPO) and Steroid Acute Regulatory Protein (StAR) via Protein Kinase A (PKA) Signaling in Hypothalamic Astrocytes

TSPO: kaleidoscopic 18-kDa amid biochemical pharmacology, control and targeting of mitochondria

Regulation of translocator protein 18kDa (TSPO) expression in health and disease states☆

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