Biomedical subjects

C Jean

Publications and source records attributed to C Jean.

At least 19 recordsLinked to original sources

PubMed1992

Adrenodemedullation does not impair the beneficial effect of physical training in streptozotocin-diabetic rats.

This study was designed to ascertain if the improvement in glucose homeostasis found in diabetic animals submitted to physical training is due to an increased secretion of epinephrine by the adrenal medullae. Male Wistar rats were surgically adrenodemedullated (ADM group) or sham-operated (SHAM group). After a 3-week recovery period, a bolus of streptozotocin (40 mg/kg) was injected intravenously (IV), and the animals presenting 1 week later with a blood glucose value between 14 and 22 mmol/L were retained in the protocol and randomly assigned to a sedentary (SHAM-DS and ADM-DS) or trained (SHAM-DT and ADM-DT) group. Physical training was done on a treadmill according to a 10-week progressive program. An IV glucose tolerance test (0.5 g/kg) was performed in previously cannulated rats, 64 hours after the last bout of exercise. Pancreatic insulin and glucagon content was also determined. In sedentary diabetic rats, adrenodemedullation had no effect on plasma glucose, insulin, or glucagon levels, neither in the basal state nor following the glucose load. Basal glucose levels were diminished by training in both SHAM (16.1 +/- 1.5 v 21.8 +/- 0.4 mmol/L; P less than .01) and ADM (12.4 +/- 1.7 v 21.1 +/- 1.2 mmol/L; P less than .01) groups, with values lower in ADM-DT than in SHAM-DT rats (P less than .05). After glucose loading, the glucose levels were significantly lower (P less than .01) throughout the test in both SHAM-DT and ADM-DT rats than in their sedentary counterparts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗

PubMed1992

The genomic organization and DNA sequence of the mouse vas deferens androgen-regulated protein gene.

The gene for mouse vas deferens protein (MVDP) is expressed, under androgenic control, exclusively in the epithelial cells of the deferent duct. As a first step in correlating cell-specific and hormonal regulations with the structure of the gene, the complete sequence of the MVDP gene (11 kb) and 0.5 kb of the 5' flanking region have been determined. The size range for the 10 exons is 78 to 168 bp, whereas that of introns is 292 to 2833 bp. A major site of transcription is located on an A residue 46 nucleotides upstream from the A of the ATG initiation codon. A TATA (CATAA) box, a CAAT box, a GC-rich motif and a (5'-TGTTCT-3') element that closely resembles the consensus sequence of the androgen response elements are present in the 5' flanking region of the MVDP gene.

Aldehyde Reductase↗

PubMed1992

In vitro androgenic induction of a major protein in epithelial cell subcultures from mouse vas deferens.

Pure epithelial cell cultures, obtained from primary culture of vas deferens tissue collected from 20- to 30-day-old mice, were amplified by subculturing the cells over 3T3 feeder layer in a serum-free defined medium. Adhesion and proliferation of epithelial cells did not require androgens, but a minimal concentration of 5.10(-7) M hydrocortisone. In that system, epithelial cells expressed cytokeratin but failed to produce the tissue specific mouse vas deferens protein (MVDP) in response to androgens. Various culture procedures and medium compositions were assayed for induction of MVDP expression. Culture onto microporous membrane inserts, which allow polarization of cells, is absolutely required for androgenic induction of MVDP. Androgen action did not require the presence of hydrocortisone, insulin, triiodothyronine, pituitary extracts, epidermal growth factor and acetylcholine. A minimal supplemented medium was then defined in which the expression of MVDP by epithelial cells in response to androgens was dose dependent. It has also been shown that this response at each concentration of dihydrotestosterone was heterogeneous at individual cell level. Highly reproducible results were obtained from epithelial cell cultures between 8th to 16th passages, showing that subcultured cells have maintained their ability to differentiate and express specialized functions.

Acetylcholine↗

PubMed1991

Androgen dependence during development of the mouse vas deferens protein mRNA.

The mRNA encoding a major protein of the mouse vas deferens (MVDP) was first detected in 10-day-old males and its concentration increased sharply between 10 and 20 days, reaching adult levels at 40 days. This increase was not associated with an increase in tissular androgen concentrations. In 30-day-old mice castrated at birth or treated with cyproterone acetate over 29 days, MVDP mRNA levels were not abolished and were similar to those measured in 10- and 20-day-old controls. These results suggest that the neonatal expression of MVDP gene is independent of androgens. In addition, precocious accumulation of MVDP mRNA could be induced by injection of excess amounts of androgens in 20- but not in 10-day-old animals. The prepubertal increase in MVDP mRNA levels is androgen-dependent but other factors may be necessary for MVDP expression.

Aldehyde Reductase↗

PubMed1991

Plasma epinephrine in chronically adrenodemedullated rats: lack of response to acute or chronic exercise.

Even if it is well established that epinephrine is a hormone originating from the adrenal medullae, the reappearance of circulating epinephrine has been reported in rats a few days after adrenodemedullation. To verify if the extra-adrenal tissue responsible for this epinephrine production can be stimulated, sham-operated or adrenodemedullated rats, either trained or kept sedentary, were submitted to an acute exercise stimulation test. Blood sampling was done before and after the test in precannulated rats for the determination of plasma epinephrine, norepinephrine, and corticosterone levels. Basal epinephrine levels were significantly reduced in trained and sedentary adrenodemedullated rats compared with their sham-operated counterparts. In response to exercise, there was no significant rise in epinephrine levels in both groups of adrenodemedullated rats. The norepinephrine levels in the basal state and in response to exercise were not altered by adrenodemedullation nor by physical conditioning. Basal corticosterone levels were similar between adrenodemedullated and sham-operated animals, either trained or kept sedentary. In response to exercise, corticosterone levels increased significantly in each group of rats but to a lesser extent in both groups of adrenodemedullated animals. These data indicate that the extra-adrenal epinephrine secretion that develops in the absence of adrenal medullae is not influenced by acute exercise nor by physical training.

Adrenal Medulla↗

PubMed1991

Lack of expression of the mRNA encoding a major protein of the mouse vas deferens after neonatal exposure to oestrogens.

We have previously characterized an androgen-inducible secretory protein from the mouse vas deferens (MVDP), and a cDNA to its mRNA has been obtained. This report describes altered MVDP gene expression after neonatal exposure to oestrogens. As shown by immunohistochemistry and Western blot analysis, MVDP was missing in the vas deferens from adult mice neonatally exposed to oestrogens. Northern blot analysis showed that the expression of MVDP mRNA was also suppressed. Exogenous testosterone was unable to stimulate MVDP production (either message or protein) in neonatally oestrogenized males. The results suggest that the alterations in gene expression in the oestrogen-exposed vas deferens reflect changes in the programme of differentiation of the organ itself.

Aldehyde Reductase↗

PubMed1991

[Characterization of cDNA and of the gene corresponding to androgen-dependent protein of the vas deferens in mice].

A 34.5 kDa abundant protein named MVDP (Mouse Vas Deferens Protein) is produced and secreted by vas deferens epithelial cells from adult mice. Steady-state levels of MVDP and its 1.4 kb mRNA are markedly decreased 30 days after castration. Testosterone treatment for 2 weeks is necessary to completely reverse the effect of castration. A cDNA encoding MVDP has been cloned and entirely sequenced. A protein of 316 amino acids encoded by an open reading frame of 948 nucleotides shows 82% homology with a human placental aldose reductase. A gene corresponding to MVDP cDNA has been recently isolated ans characterized. The gene extends over approximately 11 kb and consists of 10 exons. Its structure is very similar to that of the human aldose reductase gene. The promotor region of MVDP gene contains an androgen responsive element consensus located 97 nucleotides upstream the transcription initiation site.

Aldehyde Reductase↗

PubMed1991

Developmental and hormonal regulation of specific proteins in mouse vas deferens and seminal vesicle.

This paper is concerned with hormonal regulation of the developmental pattern of major proteins of the mouse vas deferens (mouse vas deferens protein: MVDP, 34.5 kD) and seminal vesicle (15.5, 120 and 140 kD) whose expression is regulated by testosterone at adulthood. The ontogeny of these proteins, studied by SDS-polyacrylamide gel electrophoresis, appeared to be uncoordinated. MVDP was not accumulated until animals were 20 days old and its concentration increased sharply from 20 to 30 days of age. In seminal vesicle, the 15.5 kD protein did not accumulate before day 30 whereas 120 and 140 kD proteins appeared and accumulated between 30 and 40 days. In 30-day-old mice castrated at birth or treated with cyproterone acetate over 29 days, MVDP levels were not abolished and were similar to those measured in 20-day-old males. Testosterone administration, from 1 to 10 days of age, did not induce precocious expression of MVDP. These results suggest that the neonatal expression of MVDP is independent of androgens. In seminal vesicle, the first expression of the 3 proteins studied was dependent upon testicular androgens as shown by neonatal castration and injection experiments. The marked increase in the levels of the 4 proteins studied, during sexual maturation, was not associated with quantitative or qualitative changes in tissular androgen concentrations, suggesting that other factors may be necessary for protein expression. Whereas thyroxine may induce a precocious accumulation of MVDP, prolactin had no stimulatory effect on the accumulation of proteins from vas deferens and seminal vesicle. The results suggest that during sexual maturation gene activation by androgens was progressive.

Aldehyde Reductase↗

PubMed1990

Androgen regulation of the mRNA encoding a major protein of the mouse vas deferens.

A cDNA encoding the major mouse vas deferens protein (MVDP) has been cloned and characterized. Using in situ hybridization we have identified the epithelial cells of the vas deferens as the site of synthesis of MVDP mRNA. Northern blot analysis suggests that a high level of an mRNA corresponding to the MVDP gene is present in the mouse vas deferens whereas the amount of MVDP mRNA in vas deferens of other species studied, or in other mouse tissues, even if present, is undetectable. Steady-state levels of MVDP mRNA are decreased by approximately 42% 3 days after castration but a significant hybridization signal is still observed even 50 days after castration. Testosterone treatment for 2 weeks is necessary to completely reverse the effect of castration. In vitro transcription assays on isolated nuclei showed that the hormonal induction of the MVDP gene is achieved mainly at transcriptional level.

Aldehyde Reductase↗

PubMed1990

Neonatal exposure to oestrogens alters the protein profiles and gene expression in the genital tract of adult male mice.

After neonatal administration of supraphysiological doses of oestradiol, the concentration of tissue proteins, in adult mice, was significantly reduced by 39, 45 and 56% in epididymis, vas deferens and seminal vesicle respectively. The protein profiles showed persistent alterations. In epididymis, 4 protein bands were differentially increased (14.4, 43 and 67 kDa) or reduced (24 kDa) in oestrogenized males. In vas deferens, 4 proteins were increased (14.4, 49,67 and 76 kDa) and one (34 kDa) virtually absent. In seminal vesicle, about 20 proteins of varying molecular weights (12-140 kDa) were differentially increased or decreased. Testosterone substitution, at adulthood, was unable to reverse these effects. Treatments with oestradiol during adult life induced persistent alterations in the protein profiles of the 3 organs but, in contrast to neonatal treatment, these alterations could be reversed by androgen therapy. A cDNA library has been constructed with RNA prepared from adult seminal vesicle and screened by differential hybridization. Neonatal oestrogenization strongly reduced the abundance of some mRNA species. Eleven recombinants containing putative oestrogen-sensitive sequences were isolated. Two of them, having an insert of about 500 base pairs, were used for dot-blot hybridization. Results showed that the two clones contained sequences which were differently regulated by androgens.

Aging↗

PubMed1990

[Backaches].

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Aged↗

PubMed1989

The effect of fatigue on the binding of glycolytic enzymes in the isolated gastrocnemius of Rana pipiens.

Fatigue of isolated gastrocnemius muscles from R. pipiens leads to a marked increase in the proportion of phosphofructokinase bound to the particulate fraction and a decrease in the binding of lactate dehydrogenase, pyruvate kinase, creatine phosphokinase and glyceraldehyde-3-phosphate dehydrogenase. Only the proportion of aldolase bound to the particulate fraction was unaffected by fatigue. This pattern was unchanged when fatigued muscles were extracted at pH 6.5 rather than 7.5. Thus, muscle fatigue leads to opposite changes in the binding of the glycolytic enzymes.

Animals↗

PubMed1989

Long-term alterations on the male mouse genital tract associated with neonatal exposure to cyproterone acetate biochemical data.

The effects of neonatal administration of cyproterone acetate on the growth, hormone responsiveness, DNA and protein concentrations, protein profiles, protein synthetic patterns and nuclear androgen binding sites of epididymis, vas deferens and seminal vesicles were investigated in adult mice. The weight of epididymis and seminal vesicle was significantly depressed and the reductions observed were secondary to cellular hypoplasia in epididymis and to cellular hypotrophy in seminal vesicle. The 3 organs studied showed a limited response to exogenous androgens at adulthood. When assessed by the number of cells the response of the 3 organs was similar to that of controls but it was significantly reduced from 25 to 35% when measured in term of cellular concentration of proteins. The protein profiles from homogenates of whole organs and the protein synthetic patterns after [35S]methionine incorporation, analyzed by polyacrylamide gel electrophoresis, showed reproducible persistent alterations. The total number of nuclear androgen binding sites was significantly reduced in seminal vesicles.

Aging↗

PubMed1989

Developmental pattern of androgen-regulated proteins in seminal vesicles from the mouse.

Proteins from secretions or homogenates of mice seminal vesicles were analysed by polyacrylamide gel electrophoresis. In homogenates about 15 bands were differentially induced with molecular weights (MW's) of 12, 13, 14, 15, 15.5, 71, 120 and 140 kD, or repressed molecular weights of 12.5, 14.3, 28, 30, 53, 73, 90-105 kD). The effects of castration were reversed by testosterone and dihydrotestosterone but not by oestradiol, progesterone or corticosterone. When the androgen-dependence of proteins was investigated using radioactive methionine the protein spectra showed that about 12 bands with molecular weights of 13, 13.7, 14, 15, 15.5, 16, 20.5, 24, 37, 38.5, 56, 68, 96 and 180 kD were differentially induced or repressed by androgens. Of the induced proteins, those with low molecular weight (12-15.5 kD) were accumulated in significant amounts between 20 days and 30 days, coincident with the pubertal increase of androgens in the seminal vesicles. Those induced proteins with high molecular weight (71, 120 and 140 kD) appeared between 40 days and 60 days. The androgen-repressed proteins were strongly evident in immature males, but disappeared after day 40.

Aging↗

PubMed1989

Evidence for reversible and irreversible biochemical defects in accessory sex organs and kidney of neonatally androgenized male mice.

Studies were conducted to evaluate the effects of neonatal administration of supraphysiological doses of testosterone on the growth, hormone responsiveness, dna and protein content, and protein profiles of the epididymis, vas deferens and seminal vesicles in adult mice. Results indicate that in androgenized males, testicular growth (DNA and protein content), circulating and organ androgen levels, and fertility were significantly depressed. The weights of the epididymis, vas deferens, seminal vesicle and kidney, but not that of the spleen, were significantly diminished subsequently to a reduction of protein (all organs) and DNA (epididymis, vas deferens) content. The efficacy of testosterone in promoting accessory sex organs and kidney growth, in adult castrated males, was persistently reduced in neonatally androgenized males. When assessed by DNA content, the response of all organs (except the seminal vesicle) was similar to that of controls, but it was significantly reduced from 16 to 43% when measured in terms of protein content. The protein profiles from seminal vesicles and vas deferens analysed by polyacrylamide gel electrophoresis, showed reproducible persistent alterations which could be reversed by adult androgen therapy.

Animals↗

PubMed1989

Androgen regulation of major mRNAs for proteins of the immature and adult mouse vas deferens.

When total RNA and poly (A)+ RNA extracted from the adult mouse vas deferens were translated in the rabbit reticulocyte lysate protein synthesizing system, they showed a similar electrophoretic pattern of about 20 protein bands of widely varying molecular weights. Within the total mRNA population, three functional mRNAs coding for proteins with molecular weights of 24, 34.5 and 36 kDa showed marked changes after 1 month of castration. The time-course of the response of the translatable proteins showed that while 3 days after castration the 24 and 36 kDa bands were missing, the mRNA coding for the 34.5 kDa band was markedly reduced only 20 days after castration. The negative effect of castration on the three mRNAs could be completely reversed by treatment with testosterone. When total RNA extracted from the immature mouse vas deferens was translated, the 24, 34.5 and 36 kDa protein bands were detectable in 10-day-old males and were synthesized in significant amounts between 10 and 20 days (24 and 36 kDa bands) or between 20 and 30 days (34.5 kDa band). Based on its electrophoretic and immunological properties, the 34.5 kDa protein band, which is predominant in the translation products, was identified as the major androgen-dependent protein previously described in vivo.

Age Factors↗

PubMed1988

Assay of isradipine and of its major metabolites in biological fluids by capillary gas chromatography and chemical ionization mass spectrometry.

A method is described for the determination of isradipine, a dihydropyridine calcium antagonist, and five of its metabolites in plasma and urine. The neutral compounds were extracted in toluene and analysed in a wide-bore silica capillary column. The acidic compounds were extracted in two steps, then esterified with diazomethane and assayed separately using the same column. Detection was performed by negative-ion mass spectrometry with chemical ionization. The limit of detection of isradipine was 0.04 ng/ml when the compound was determined alone and 0.7 ng/ml when its oxidized metabolite was determined simultaneously. The limits of detection of the metabolites in plasma ranged from 0.15 to 2 ng/ml. The method was successfully used in conventional pharmacokinetic studies and in a multicentre study of population pharmacokinetics.

Calcium Channel Blockers↗

PubMed1988

Prolonged influence of a neonatal cyproterone acetate treatment on renal androgen binding in mice.

To determine whether neonatal endogenous androgens influence adult renal androgen binding, newborn male mice were injected from 1 to 10 days of age with cyproterone acetate and newborn females with testosterone from 1 to 10 days and from 20 to 40 days of age. In controls, at adulthood, the total cellular androgen receptor content was significantly higher in males (1700 +/- 200 receptors per cell) than in females (1060 +/- 50) and, as expected, the nuclear receptor content was 12-fold higher in males. While the total number of receptors (1650 +/- 200 per cell) was unchanged in adult males neonatally treated with cyproterone acetate, their distribution between cytosol and nucleus was similar to that in control females despite normal circulating and renal testosterone levels. The nuclear receptors represented 50, 7 and 11% of the total receptors in control males, control females and cyproterone acetate-treated males, respectively. The very low levels of nuclear receptors present in the kidney of cyproterone acetate-treated males probably explain the decreased sensitivity of this organ to testosterone. The nuclear receptor accumulation measured in adult animals after a single injection of testosterone did not seem to be affected by neonatal hormonal manipulations.

Age Factors↗