Full-Length cDNA Sequence of a Progesterone Membrane-Binding Protein from Porcine Vascular Smooth Muscle Cells

Falkenstein, Elisabeth; Meyer, Christiane; Eisen, Christoph; Scriba, Peter Christian; Wehling, Martin

doi:10.1006/bbrc.1996.1761

Cited by 201 publications

(137 citation statements)

References 0 publications

Supporting

Mentioning

131

Contrasting

Unclassified

Order By: Relevance

“…Based on evidence for a non-genomic mode of action we determined if this putative receptor is expressed in rat skeletal muscle. In line with a previous study on pigs [27], Pgrmc1 mRNA was found in liver and spleen, with a …”

Section: Expression Of Pgrmc1supporting

confidence: 91%

Progesterone impairs cell respiration and suppresses a compensatory increase in glucose transport in isolated rat skeletal muscle: a non-genomic mechanism contributing to metabolic adaptation to late pregnancy?

et al. 2007

View full text Add to dashboard Cite

Aims/hypothesis The aim of the study was to gain better insight into the mechanisms responsible for impaired glucose metabolism during late pregnancy. We explored the direct effects of progesterone on glucose metabolism of skeletal muscle. Methods Specimens of skeletal muscle from untreated rats were incubated with progesterone and rates of substrate fluxes through the various pathways of glucose metabolism were analysed. Results Progesterone dose-dependently reduced the rates of glucose and pyruvate oxidation (insulin-stimulated rates after 5 h of exposure to 1 and 10 μmol/l progesterone: glucose oxidation, −6±4%, NS, and −39±4%, p<0.001; pyruvate oxidation, −28±2% and −55±4%, p<0.001 each) and increased lactate release (+28±4% and +58±9%, p<0.005 each), which indicated inhibition of mitochondrial respiratory function. Impairment of cell respiration, e.g. by the specific inhibitor rotenone, is known to trigger a compensatory increase in glucose transport, but this response was blunted in the case of progesterone (change of glucose transport in response to 10 μmol/l progesterone vs 60 nmol/l rotenone, both causing a reduction in glucose oxidation by −39%: progesterone, +14±8% vs rotenone, +84±23%, p< 0.03). Further experiments dealt with the underlying mechanisms and revealed a rapid mode of action (50 μmol/l progesterone, reduction in insulin-stimulated glucose oxidation after 30 min: −29±7%, p<0.01) not affected by blockers of gene expression or the nuclear progesterone receptor. Conclusions/interpretation Progesterone inhibits cell respiration and at the same time suppresses a compensatory increase in glucose transport, causing cellular carbohydrate deficiency in isolated rat skeletal muscle. This effect is mediated by a direct, rapid and non-genomic mechanism and could contribute to pregnancy-associated changes in glucose homeostasis.

show abstract

Section: Expression Of Pgrmc1supporting

confidence: 91%

Progesterone impairs cell respiration and suppresses a compensatory increase in glucose transport in isolated rat skeletal muscle: a non-genomic mechanism contributing to metabolic adaptation to late pregnancy?

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Both proteins localize to the endoplasmic reticulum 29,32 : PGRMC1 has been reported to bind progesterone 24 , and Insig-1 is a negative regulator of sterol biosynthesis acting in the SCAP-SREBP system 29 . The physiological implication of this new interaction is under investigation in our laboratory.…”

Section: Discussionmentioning

confidence: 99%

“…We transfected cells with a plasmid encoding the membrane protein PGRMC1 (ref. 24) and assessed whether methionine, valine, leucine or isoleucine competed for cross-linking by photo-Leu and photo-Met. We observed competition for cross-linking by photo-Leu (Fig.…”

Section: Synthesis and Biosynthetic Incorporation Into Proteinsmentioning

confidence: 99%

“…The complex is located in the endoplasmic reticulum, in which it responds to low cholesterol levels. PGRMC1, a progesterone-binding membrane protein of the endoplasmic reticulum 24,32 , might be another protein involved in this process. In particular, we suspected that it might interact directly with Insig-1.…”

Section: Synthesis and Biosynthetic Incorporation Into Proteinsmentioning

confidence: 99%

See 1 more Smart Citation

Photo-leucine and photo-methionine allow identification of protein-protein interactions in living cells

2005

View full text Add to dashboard Cite

Protein-protein interactions are the key to organizing cellular processes in space and time. The only direct way to identify such interactions in their cellular environment is by photo-crosslinking. Here we present a new strategy for photo-cross-linking proteins in living cells. We designed two new photoactivatable amino acids that we termed photo-methionine and photo-leucine based on their structures and properties closely resembling the natural amino acids methionine and leucine, respectively. This similarity allows them to escape the stringent identity control mechanisms during protein synthesis and be incorporated into proteins by the unmodified mammalian translation machinery. Activation by ultraviolet light induces covalent cross-linking of the interacting proteins, which can be detected with high specificity by simple western blotting. Applying this technology to membrane protein complexes, we discovered a previously unknown direct interaction of the progesterone-binding membrane protein PGRMC1 with Insig-1, a key regulator of cholesterol homeostasis.

show abstract

“…Since the action of progesterone on follicle assembly does not appear to be mediated by the nuclear progesterone receptor, the potential role of the cell surface membrane progesterone receptor is considered. Membrane progesterone receptors were first described in the spotted sea trout (Patino & Thomas 1990) and then later in the pig (Falkenstein & Meyer 1996). These membrane steroid receptors have been found to mediate rapid nongenomic responses to steroid hormones (Falkenstein & Tillmann 2000, Sutter-Dub 2002.…”

Section: Introductionmentioning

confidence: 99%

Interactions between progesterone and tumor necrosis factor-α in the regulation of primordial follicle assembly

Nilsson

Stanfield²,

Skinner

2006

Reproduction

View full text Add to dashboard Cite

Follicle assembly is the process by which groups or 'nests' of oocytes break down to form primordial follicles. The size of the primordial follicle pool is the major determinant of the reproductive lifespan of a female. Previously, progesterone (P 4 ) has been shown to inhibit follicle assembly, while tumor necrosis factor-a (TNFa) has been shown to promote the apoptosis that is necessary for follicle assembly. The present study examines how TNFa and progesterone interact to regulate primordial follicle assembly. Ovaries were collected from newborn rats and placed in organ culture to examine the actions of P 4 and TNFa. P 4 was found to decrease primordial follicle assembly and increase the percentage of unassembled oocytes both in vitro and in vivo. TNFa treatment did not change the proportion of assembled follicles in cultured ovaries, but blocked the ability of P 4 to inhibit follicle assembly. Microarray analysis of the ovarian transcriptome revealed that progesterone treatment of the ovaries altered the expression of 513 genes with 132 only expressed after P 4 treatment and 16 only expressed in control ovaries. The majority of genes were up-regulated greater than twofold over control, with a small subset of 16 genes down-regulated. Categories of genes affected by P 4 are described including a group of extracellular signaling factors. The progesterone receptors expressed at the time of follicle assembly included the surface membrane progesterone receptors PGRMC1, PGRMC2, and RDA288. The nuclear genomic P 4 receptor was not expressed at appreciable levels. Progesterone increased the expression of several genes (TANK, NFkB, Bcl2l1, and Bcl2l2) involved in a signaling pathway that promotes cell survival and inhibits apoptosis. Observations indicate that P 4 acts through the surface membrane progesterone receptors to regulate primordial follicle assembly, and that TNFa can override the inhibitory actions of P 4 on follicle assembly. A major mechanism involved in the actions of P 4 is an increase in cell survival genes and inhibition of the apoptosis pathway. Observations provide insight into the hormonal regulation of primordial follicle assembly and lead to novel approaches to potentially manipulate follicle assembly and reproductive capacity.

show abstract

Full-Length cDNA Sequence of a Progesterone Membrane-Binding Protein from Porcine Vascular Smooth Muscle Cells

Cited by 201 publications

References 0 publications

Progesterone impairs cell respiration and suppresses a compensatory increase in glucose transport in isolated rat skeletal muscle: a non-genomic mechanism contributing to metabolic adaptation to late pregnancy?

Progesterone impairs cell respiration and suppresses a compensatory increase in glucose transport in isolated rat skeletal muscle: a non-genomic mechanism contributing to metabolic adaptation to late pregnancy?

Photo-leucine and photo-methionine allow identification of protein-protein interactions in living cells

Interactions between progesterone and tumor necrosis factor-α in the regulation of primordial follicle assembly

Contact Info

Product

Resources

About