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P Robel

Publications and source records attributed to P Robel.

At least 91 records · Page 5Linked to original sources

Effects of progesterone and tamoxifen on glucocorticosteroid-induced egg-white protein synthesis in the chick oviduct.

A single injection of either natural (cortisol, corticosterone) or synthetic [dexamethasone (DEX), triamcinolone acetonide] glucocorticosteroids to estradiol-primed, withdrawn chicks, resulted in a dose-dependent increase in the relative rates of ovalbumin and conalbumin synthesis. The simultaneous injection of equal doses of DEX and progesterone resulted in an additive effect on the relative rate of ovalbumin synthesis at all doses tested (range: 0.05-15 mg/chick), even when the induction of ovalbumin synthesis was maximal at 6 h, for either hormone injected alone. Moreover, the simultaneous injection of DEX and progesterone yielded an additive effect on the relative rates of ovalbumin and conalbumin gene transcription. The nonsteroidal antiestrogen tamoxifen does not increase ovalbumin synthesis and only slightly increases conalbumin synthesis. The simultaneous injection of tamoxifen and DEX potentiated the effect of DEX on the relative rates of ovalbumin and conalbumin synthesis, and amplified the DEX-induced increase in the relative rates of ovalbumin and conalbumin gene transcription. These results were supported by morphological studies carried out after 4 days of stimulation, which showed an increased accumulation of secretory granules in the magnum cells of the oviducts of chickens treated by tamoxifen plus DEX, as compared to that observed in chickens injected with DEX alone. In conclusion, these results suggest that glucocorticosteroids likely act through a mechanism distinct from that of sex steroids, and may modulate the effects of the latter on egg-white protein synthesis.

Animals↗

Endometrial and pituitary responses to the steroidal antiprogestin RU 486 in postmenopausal women.

The effects of the antiprogestin RU 486 on the human endometrium were investigated. Seventeen postmenopausal women were injected with estradiol (E2) benzoate (0.625 mg/day) for 15 days. Progesterone (P) (25 mg/day) and/or RU 486 (100 or 200 mg/day) were given to groups of 2-3 women during the last 6 days of E2 benzoate treatment. Serial blood samples were drawn for the measurement of plasma E2, P, and LH and FSH. An endometrial biopsy was performed on the last day of treatment, and processed for histology or for assays of DNA polymerase alpha, E2-dehydrogenase (E2DH), and P receptor (PR). Treatment with E2 benzoate alone resulted in a marked decrease of plasma gonadotropins; in those patients who received either P, RU 486, or both, in addition to E2 benzoate, the concentrations of plasma LH and FSH were further decreased to premenopausal levels. In absence of glycerol, the affinity of RU 486 for the endometrial PR (Kd = 0.8 nM) was higher than that of P (Kd = 1.2 nM). Glycerol decreased markedly the affinity of RU 486, whereas the affinity of P for the PR was unchanged. RU 486 had negligible affinity for plasma transcortin. Either P or RU 486, but not both together, induced secretory changes in the endometrium as determined from histologic sections of tissue biopsies. Either P or RU 486 decreased DNA polymerase alpha and increased E2-DH activities in the endometrium. Unexpectedly, when P and RU 486 were given together. E2-DH activity remained at the level found in E2-treated women. In vitro cultures of proliferative endometrium treated with the synthetic progestagen R 5020 or with RU 486 also had increased E2-DH activity; RU 486 counteracted R 5020 effects. We conclude that, contrary to previous results with experimental animals, the anti-P RU 486 has some progestomimetic activity in humans under specific conditions. Paradoxically, when given together with P, RU 486 lost most of its progestomimetic activity in the endometrium and behaved as a pure antagonist.

Adult↗

[Circadian course of delta 5,3 beta-hydroxysteroids and glucocorticosteroids in the plasma and brain of rats].

Corticosterone (B), pregnenolone (P) and dehydroepiandrosterone (D) undergo circadian variations in the rat plasma and brain. When the data are interpreted by the Cosinor method, the acrophases of P in brain and of D in plasma significantly precede the acrophase of B. The asynchrony of delta 5-3 beta-hydroxysteroid and glucocorticosteroid rhythms brings an additional argument in favor of separate regulatory mechanisms.

Animals↗

Estrogen-like effects of combined dexamethasone and tamoxifen in the chick oviduct.

The effects of dexamethasone alone on withdrawn chick oviduct weight, DNA, protein content and progesterone receptor concentration were barely detectable, whereas ovalbumin and conalbumin synthesis were increased. When dexamethasone and tamoxifen were combined, a marked increase of total proteins, including egg white proteins, DNA and wet weight occurred. Progesterone receptor also was increased. The most striking result was the stimulation of DNA polymerase-alpha activity by combined dexamethasone and tamoxifen, whereas either compound was completely ineffective.

Animals↗

Characteristics of separated epithelial and stromal subfractions of prostate: I. Rat ventral prostate.

These studies were initiated with the objective of isolating epithelial and stromal cells of human prostatic tissue in undamaged state, in order to study the cellular distribution of steroid receptors in benign prostatic hyperplasia (BPH) relative to normal prostate. Initial experiments showed that when BPH tissue immersed in tissue culture media was progressively fragmented by various cutting procedures, epithelial elements were selectively released as clumps of variable size and individual cells, but that a large percentage of these cells were damaged, as evidenced by their failure to exclude trypan blue (TB). These observations suggested that if tissue fragmentation were carried out under defined conditions that minimize cell damage, BPH subfractions might be obtained containing a large percentage of undamaged cells. To determine conditions of tissue fragmentation which result in maximal recovery of epithelial cells which exclude TB, rat ventral prostate (RVP) was chosen as a model system. Experiments with RVP revealed that maximal yields of such cells were obtained in "large" epithelial clumps (greater than 30 cells per clump) released under the following conditions: (1) chopping the tissue with razor blades in a large volume (2 ml/100 mg RVP) of a Ca2+-free tissue culture medium ( Joklik 's-MEM) containing 1% casein, (2) carrying out the entire fractionation procedure in the cold, and (3) maintaining a 1% casein concentration in the medium during chopping, as well as in subsequent washing procedures, to protect cells from proteolytic activity. In large epithelial clumps, cells in the interior of the clump were not stained by TB but the cells at the periphery of the clump were freely permeable to TB. Single epithelial cells and small epithelial clumps (3-10 cells) released by razor blade fragmentation were also permeable to TB. When large epithelial clumps were incubated at 20 degrees C for 90 min, the clumps disaggregated into smaller clumps and morphologically intact single cells, which did not exclude TB. The residual tissue fragments remaining after chopping contained the bulk of stromal cells plus some epithelial elements. The latter could be removed by gentle rubbing of the fragments on a sieve in the presence of medium. The stromal fraction thus obtained consisted of stromal cells, embedded in mesenchymal matrix, which were not stained by TB and appeared normal when examined histologically by light microscopy.(ABSTRACT TRUNCATED AT 400 WORDS)

Acid Phosphatase↗

Characteristics of separated epithelial and stromal subfractions of prostate: II. Human prostate.

Surgical samples of human benign prostatic hyperplasia tissue (BPH) were fractionated into epithelial clumps and stromal fractions, using the "optimal" tissue dissociation procedure developed for rat prostate described in the preceding report. The separated cellular fractions were compared to control unfractionated tissue (wherein extracellular secretory products had been removed) with respect to the concentrations of androgen receptor and enzyme markers on a DNA basis; cell damage was also evaluated by light and electron microscopy (EM). EM revealed extensive cell damage in epithelial clumps and stromal fractions, which had appeared normal when examined by light microscopy. Damage to the ultrastructure of individual epithelial cells present in clump fractions was very variable, involving vacuolization of the cytoplasm and condensation of nuclear chromatin in some cells, vacuolization of just the cytoplasm in other cells; only a small fraction of the cells in clumps had normal ultrastructure. Ultrastructural damage to stromal cells was much greater in fibroblasts than in muscle fibers. The cell damage observed in both subfractions of human prostate was associated with a marked degree of receptor loss. The mean decreases in the number of androgen receptors per unit DNA relative to control unfractionated tissue was 68.5 and 62.5% recovered in epithelial and stromal fractions, respectively. Measurement of various enzymes as "markers" revealed that acid phosphatase activity (per unit DNA) was associated exclusively with the epithelial clump fraction. Prolyl hydroxylase and myosin ATPase activities (per unit DNA) were restricted to the stromal fraction. The limitations of using mechanically separated subfractions of human prostate tissue for evaluation of the cellular distribution or the initial concentration of steroid receptors in human prostate tissue are discussed.

Acid Phosphatase↗

The "dysharmonic luteal phase" syndrome: endometrial progesterone receptor and estradiol dehydrogenase.

The dysharmonic luteal phase (DLP) syndrome is defined by delayed endometrial maturation despite normal plasma progesterone (P) values. In ten patients with DLP the actual date of the endometrial biopsy, dated retrospectively, was 24.7 +/- 2.3 days, whereas the histologic date was 20.0 +/- 2.6 days. The concentration of cytosolic P receptor in DLP endometrium tended to be lower, whereas the concentration of nuclear receptor was significantly higher in DLP than in seven matched patients with normal luteal phases. Endometrial estradiol-dehydrogenase activities were identical in both groups. The DLP syndrome cannot be explained by a decreased sensitivity of the endometrium to P and is probably merely functional in nature.

17-Hydroxysteroid Dehydrogenases↗

[Viper bites].

Explore the source record for details and available documents.

Adult↗

Pregnenolone and its sulfate ester in the rat brain.

Pregnenolone (P) and its sulfate ester (PS) have been characterized in the brain of adult male rats. The concentration of P (38.4 +/- 6.9 and 22.1 +/- 2.9 ng/g, mean +/- S.D., in anterior and posterior brain, respectively) exceeded that of PS in brain (15.8 +/- 3.0 and 5.7 +/- 2.1 ng/g in the same fractions) and largely those of P and PS in plasma (1.3 +/- 0.2 and 1.4 +/- 0.3 ng/g, respectively). The level of P in brain was much larger than that of dehydroepiandrosterone sulfate (DS), characterized and measured previously (Corpéchot et al.). Brain P and PS levels did not seem to depend on steroidogenic gland secretion: no meaningful difference occurred in brain 15 days after adrenalectomy plus orchiectomy, compared with sham-operated controls. It is proposed that, as that of DS (ref. 5) P and PS formation or accumulation (or both) in the rat brain depend on in situ mechanisms unrelated to the peripheral endocrine gland system.

Animals↗

Androgen receptors in rat and human prostate.

In intact adult rats almost all androgen receptor (AR) sites of the rat ventral prostate (RVP) are occupied by endogenous dihydrotestosterone, and about 80% of these sites are nuclear. Nuclear AR disappears rapidly after castration (half-life of 3 h). The amount of cytosolic AR does not change within the initial 36 h, then markedly decreases during the next 2-5 days. An early and specific action of androgen is a remarkable increase of its own receptor. RVP also contains an estradiol receptor (ER) which rapidly disappears after castration and which, contrary to AR, is predominantly localized in the cytosol of stromal elements. The published procedures for steroid receptors grossly underestimate receptors concentrations in normal (NHP) and hyperplastic (BPH) human prostate. We have recently established a reliable method for the measurement of total AR, and we have found no difference in AR concentrations between NHP and BPH. BPH also contains a progesterone receptor and an elusive ER. Finally, we have used specific immunoglobulins in sex hormone binding plasma protein (SBP) for the demonstration of SBP-like immunoreactivity by the indirect immunofluorescence technique. The specific antigenic material was exclusively localized in the cytoplasm of BPH epithelial cells.

Animals↗

[Dehydroepiandrosterone inhibits aggressive behavior in castrated male mice].

Group-housed triads of castrated male Mice attack lactating female intruders. We had previously observed that testosterone or oestradiol inhibited this aggressive behavior. The Mouse brain contains relatively large mounts of dehydroepiandrosterone (D), therefore we have investigated the behavioral effect of this steroid. D was inactive in intact males, whereas it markedly inhibited the attack directed by castrated males, when delivered by an osmotic minipump at the dose of 83 micrograms/day. D was also given by daily injections for 15 days in oil solution, the dose of 80 micrograms/day decreased attacks of castrated males below the level of intact controls, the dose of 40 micrograms was partly active, whereas the dose of 20 micrograms was inactive.

Aggression↗

[Administration of diethylstilbestrol during pregnancy, a public health problem].

The analysis of the health risks associated with the administration of diethylstilbestrol (DES) during pregnancy (for the prevention or treatment of threatened abortions) has been largely published. Concerning mothers, a relationship between DES exposure during pregnancy and risk of cancer is unproved. However, existing studies are sufficient cause for serious concern over drug's carcinogenic potential, and further follow-up studies are required. Concerning daughters, a clear association between in utero exposure to DES and clear cell adenocarcinoma of the vagina or cervix is established (incidence between 0.14 and 1.4 per 1000 through age 24). The risk for squamous cell cancer of the vagina and cervix does not seem to be increased. Cervico-vaginal adenosis is frequent (20% to 60% of exposed subjects). This is not a pre-cancerous lesion, its spontaneous evolution is towards regression. No treatment is prescribed. Morphological changes of the genital tract have been described, their consequences on fertility and pregnancy are not clear. Concerning sons, an excess of genital abnormalities (especially of the epididymis and undescended testis) has been reported, but information on the fertility implications of these findings is not available. There is no evidence of an increased risk of testicular cancer. The analysis of all these informations should allow to bring up a policy to take into account these risks in the population.

Adult↗

Androgen-dependent regulation of androgen nuclear receptor in the rat ventral prostate.

Methods have been developed for the measurement of nonradioactive or radioactive dihydrotestosterone (DHT) bound to androgen receptor in rat ventral prostate nuclei (DHTRn). Using 1-day-castrated adult Sprague-Dawley rats (300--320 g body weight), the effects of testosterone (T) on nuclear androgen receptor formation were investigated in the absence and presence of cycloheximide or emetine. DHTRn was measured 4 h after injection of increasing amounts of T, and a maximal value of 14.6--17.8 pmol DHTRn/prostate was reached with doses of T greater than 37.5 micrograms. The amount of DHTRn 30 min after administration of 75 micrograms T was already 3 times greater than the concentration of cytosol receptor initially present in untreated castrated rats (2.0 +/- 0.3 pmol/prostate). In rats that received 2 mg cycloheximide ip 30 min before T, DHTRn did not exceed 5 pmol/prostate; in rats pretreated with 10 mg emetine administered at 1 h and 15 min before T, DHTRn did not exceed 8 pmol/prostate. These results suggest a two-component mechanism: 1) the translocation of preexisting cytosolic-receptor-hormone complexes to the nucleus; and 2) de novo formation of androgen receptor dependent on protein synthesis, which upon interaction with exogenous steroid is likewise accumulated in the nucleus. Progesterone (1 mg) and estradiol (0.6 mg) were also injected in amounts calculated to produce the same degree of occupancy of androgen receptor sites as did T. With both of these steroids, nuclear accumulation of androgen receptor was observed, but neither progesterone nor estradiol induced de novo synthesis of androgen receptor.

Animals↗