Steroid hormone biosynthesis is acutely regulated by pituitary trophic hormones and other steroidogenic stimuli. This regulation requires the synthesis of a protein whose function is to translocate ...cholesterol from the outer to the inner mitochondrial membrane in steroidogenic cells, the rate-limiting step in steroid hormone formation. The steroidogenic acute regulatory (StAR) protein is an indispensable component in this process and is the best candidate to fill the role of the putative regulator. StAR is expressed in steroidogenic tissues in response to agents that stimulate steroid production, and mutations in the StAR gene result in the disease congenital lipoid adrenal hyperplasia, in which steroid hormone biosynthesis is severely compromised. The StAR null mouse has a phenotype that is essentially identical to the human disease. The positive and negative expression of StAR is sensitive to agents that increase and inhibit steroid biosynthesis respectively. The mechanism by which StAR mediates cholesterol transfer in the mitochondria has not been fully characterized. However, the tertiary structure of the START domain of a StAR homolog has been solved, and identification of a cholesterol-binding hydrophobic tunnel within this domain raises the possibility that StAR acts as a cholesterol-shuttling protein.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The steroidogenic acute regulatory or StAR protein has been shown to be instrumental in the acute regulation of steroid hormone biosynthesis through its action in mediating cholesterol transfer to ...the inner mitochondrial membrane and the cholesterol side chain cleavage enzyme system. Since the time of its cloning in 1994, a number of studies have been performed which underscore the important role that this protein plays in steroidogenesis. While it is now quite apparent that StAR fulfills the criteria for the acute regulator as proposed by early studies, several crucial areas remain poorly understood. This list is topped by the so far intractable nature of the mechanism of action of StAR in transferring cholesterol to the P450scc enzyme. A second area which should prove to be of great interest is that of further understanding the regulation of the StAR gene which, like many genes, is quite complex. Lastly, with the recent demonstration of StAR being present in the brain, determining if StAR has a role in the synthesis of neurosteroids should prove to be of great importance.
The steroidogenic acute regulatory protein is indispensable for the biosynthesis of steroid hormones. Steroidogenic acute regulatory protein mediates the rate-limiting step in steroidogenesis, the ...transfer of cholesterol from the outer mitochondrial membrane to the inner mitochondrial membrane where it is cleaved to pregnenolone. Its essential role in steroidogenesis was shown when it was discovered that mutations in the steroidogenic acute regulatory protein gene in humans cause the lipoid form of congenital adrenal hyperplasia, a potentially lethal disease resulting from an inability to synthesize steroids. Also, the steroidogenic acute regulatory protein null mouse has a phenotype that is essentially the same as that observed with human mutations. Studies on the regulation of the expression of the steroidogenic acute regulatory protein gene has enjoyed considerable progress, yet the complexity of this regulation indicates that much work remains. The mechanism whereby steroidogenic acute regulatory protein mediates the transfer of cholesterol to the inner mitochondrial membrane remains a mystery, but the recent solving of the structure of the cholesterol transferring domain of a steroidogenic acute regulatory protein homolog coupled with structure-function studies of steroidogenic acute regulatory protein in natural and synthetic membranes has allowed for at least two models to be proposed. This review will briefly attempt to summarize what is currently known about the regulation of the steroidogenic acute regulatory protein gene and its mechanism of action, fully understanding that in both areas considerable gaps in our knowledge remain.
Steroid hormones are synthesized in the adrenal gland, gonads, placenta and brain and are critical for normal reproductive function and bodily homeostasis. The steroidogenic acute regulatory (StAR) ...protein regulates the rate-limiting step in steroid biosynthesis, i.e. the delivery of cholesterol from the outer to the inner mitochondrial membrane. The expression of the StAR protein is predominantly regulated by cAMP-dependent mechanisms in the adrenal and gonads. Whereas StAR plays an indispensable role in the regulation of steroid biosynthesis, a complete understanding of the regulation of its expression and function in steroidogenesis is not available. It has become clear that the regulation of StAR gene expression is a complex process that involves the interaction of a diversity of hormones and multiple signaling pathways that coordinate the cooperation and interaction of transcriptional machinery, as well as a number of post-transcriptional mechanisms that govern mRNA and protein expression. However, information is lacking on how the StAR gene is regulated in vivo such that it is expressed at appropriate times during development and is confined to the steroidogenic cells. Thus, it is not surprising that the precise mechanism involved in the regulation of StAR gene has not yet been established, which is the key to understanding the regulation of steroidogenesis in the context of both male and female development and function.
Abstract
The ALICE muon trigger (MTR) system consists of 72 Resistive
Plate Chamber (RPC) detectors arranged in two stations, each
composed of two planes with 18 RPCs per plane. The detectors are
...operated in maxi-avalanche mode using a mixture of 89.7%
C
2
H
2
F
4
, 10% i-C
4
H
10
and 0.3% SF
6
. A
number of detector performance indicators, such as efficiency and
dark current, have been monitored over time throughout the LHC Run2
(2015–18). While the efficiency showed very good stability, a steady
increase in the absorbed dark current was observed.
Since the end of 2018, the LHC has entered a phase of long shutdown, during which the ALICE experiment will be upgraded to cope with the next phase of data taking, expected in 2021. The MTR is undergoing a major upgrade of the front-end and readout electronics, and will change its functionalities, becoming a Muon Identifier 1. Only the replacement of the most irradiated RPCs is planned during the upgrade. It is therefore important to perform dedicated studies to gain further insights into the status of the detector. In particular, two RPCs were flushed with pure Ar gas for a prolonged period of time and a plasma was created by fully ionizing the gas. The output gas was analyzed using a Gas Chromatograph combined with a Mass Spectrometer and the possible presence of fluorinated compounds originating from the interaction of the plasma with the detector inner surfaces has been assessed using an Ion-Selective Electrode station.
This contribution will include a detailed review of the ALICE muon RPC performance at the LHC;
the procedure and results of the argon plasma test, described above, are also discussed.
Mutations in the DAX-1 gene are responsible for congenital X-linked adrenal hypoplasia, a disease that is associated with hypogonadotropic hypogonadism,. DAX-1 expression is tissue-specific and is ...finely regulated throughout development, suggesting that it has a role in both adrenal and gonadal function. DAX-1 is an unusual member of the nuclear-receptor superfamily of transcription factors which contains no canonical zinc-finger or any other known DNA-binding motif. Binding sites for DAX-1 are found in the promoters of the dax-1 and StAR (for steroidogenic acute regulatory protein) genes. Here we show that DAX-1 binds DNA and acts as a powerful transcriptional repressor of StAR gene expression, leading to a drastic decrease in steroid production. We provide in vitro and in vivo evidence that DAX-1 binds to DNA hairpin structures. Our results establish DAX-1 as the first member of the nuclear receptor superfamily with novel DNA-binding features and reveal that it has regulatory properties critical to the understanding of its physiological functions.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The facile preparation of oxygen-generating microparticles (M) consisting of Polycaprolactone (PCL), Pluronic F-127, and calcium peroxide (CPO) (PCL-F-CPO-M) fabricated through an electrospraying ...process is disclosed. The biological study confirmed the positive impact from the oxygen-generating microparticles on the cell growth with high viability. The presented technology could work as a prominent tool for various tissue engineering and biomedical applications.
The oxygen-generated microparticles fabricated through electrospraying processes were thoroughly characterization through various methods such as X-ray diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR) analysis, and scanning electron microscopy (SEM)/SEM-Energy Dispersive Spectroscopy (EDS) analysis.
The analyses confirmed the presence of the various components and the porous structure of the microparticles. Spherical shape with spongy characteristic microparticles were obtained with negative charge surface (ζ = -16.9) and a size of 17.00 ± 0.34 μm. Furthermore, the biological study performed on rat chondrocytes demonstrated good cell viability and the positive impact of increasing the amount of CPO in the PCL-F-CPO-M.
This technological platform could work as an important tool for tissue engineering due to the ability of the microparticles to release oxygen in a sustained manner for up to 7 days with high cell viability.
Congenital lipoid adrenal hyperplasia is an autosomal recessive disorder that is characterized by impaired synthesis of all adrenal and gonadal steroid hormones. In three unrelated individuals with ...this disorder, steroidogenic acute regulatory protein, which enhances the mitochondrial conversion of cholesterol into pregnenolone, was mutated and nonfunctional, providing genetic evidence that this protein is indispensable for normal adrenal and gonadal steroidogenesis.
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