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Biomedical subjects

P Robel

Publications and source records attributed to P Robel.

At least 109 records · Page 6Linked to original sources
PubMed1981

[Free and sulfo-conjugated dehydroepiandrosterone in the brain of mice with myelin biosynthesis disorders].

Dehydroepiandrosterone, either unconjugated (D) or conjugated to sulfuric acid (DS), has been identified in the brain of male Mice; DS had been previously found in Rat brain. DS amounts in posterior brain, were 0.8-2.0 ng/g in controls, and very much lower in dysmyelinic jimpy and quaking Mice of the same age. Conversely, amounts of D were increased in affected Mice, suggesting an impaired sulfoconjugation. Results may be explained by accumulation of D and DS in brain, unrelated to the endocrine system.

Animals↗
PubMed1981

Clinical investigation of the menstrual cycle. III. Clinical, endometrial, and endocrine aspects of luteal defect.

This study was intended to correlate different clinical and biologic parameters to better define luteal insufficiency (LI) and to contribute to a better understanding of its origin. Endometrial patterns were used as the basis for classification of clinical cases. Of 328 outpatients with menstrual disorders and/or infertility, 88 were considered to have LI. Their cycles were compared with 79 normal cycles. Two different principal endometrial patterns of LI are described: pure LI, when the endometrium is more than 2 days out of phase; and LI with persistent estrogenic influence, when the histologic estrogenic stigmata are excessive during the luteal phase. Basal body temperature charts demonstrated menstrual cycle disturbances: either ovulation delay or a slow increase in temperature (longer than 2 days). Plasma steroid concentrations also demonstrated a perturbation of the entire menstrual cycle: progesterone levels were statistically significantly lower in LI than in normal cycles and this defect was worse when the estrogenic influence was persistent; the preovulatory estradiol peak was disturbed in all circumstances, as was the concentration of endometrial steroid receptors. These simultaneous abnormalities strongly suggest a central origin of LI.

Adult↗
PubMed1981

Characterization and measurement of dehydroepiandrosterone sulfate in rat brain.

Dehydroepiandrosterone (3 beta-hydroxy-5-androsten-17-one, I) sulfate (Ia) has been characterized in the anterior and the posterior parts of the brain of adult male rats. Its level (1.58 +/- 0.14 and 4.89 +/- 1.06 ng/g, mean +/- SD, in anterior and posterior brain, respectively) largely exceeded that of I in brain (0.42 +/- 0.10 and 0.12 +/- 0.03 ng/g in anterior and posterior brain, respectively) and of Ia in plasma (0.26 +/- 0.13 ng/ml). Brain Ia level did not seem to depend on adrenal secretion; it was unchanged after administration of corticotropin or dexamethasone for 3 days, and no meaningful change occurred in brain 15 days after adrenalectomy plus orchiectomy, compared with sham-operated controls. In contrast, stress conditions prevailing 2 days after adrenalectomy plus orchiectomy or after the corresponding sham operation resulted in a significantly increased concentration of Ia in the brain. Changes of Ia level in brain occurred irrespective of changes in corresponding plasma samples. It is proposed that Ia formation or accumulation (or both) in the rat brain depends on in situ mechanisms unrelated to the peripheral endocrine gland system.

Adrenalectomy↗
PubMed1981

Androgen and estrogen receptors in rat ventral prostate epithelium and stroma.

Estrogen and androgen receptors have been investigated in rat ventral prostate epithelium and stoma. High speed supernatants were prepared from unfractionated or fractionated prostates. Cytosols from intact rats were incubated with 2 nM 3H-estradiol (E2) in presence of 80 nM dihydrotestosterone (DHT), and cytosols from 1 day castrated rats were incubated with 2 nM 3H-DHT, at 0 C for 4 h. They were submitted to ultracentrifugation on glycerol-Tris gradients. The amounts of hormones bound to the saturable 8S binding components were determined on a comparative basis. The values for E2-receptor in intact rats were 2.3, 15.4 and 5.9 fmol/mg cytosol protein in unfractionated prostate, stroma and epithelium, respectively. The corresponding values for DHT-binding were 31.9, 17.2 and 29.2 fmol/mg protein. In addition, Scatchard analysis of saturable E2 and DHT binding, using the protamine precipitation technique, essentially confirmed the results of glycerol gradients, and led to the conclusion that, contrary to androgen receptor, the major part of estradiol receptor is localized in stroma.

Animals↗
PubMed1980

Assay of nuclear estradiol receptor by exchange on glass fiber filters.

A glass fiber filter exchange assay for nuclear estradiol receptor in human endometrium has been developed. It permits both exchange and measurement of bound radioactivity to be performed without any transfer of the nuclear preparations. Suspensions of nuclei containing estradiol-receptor complexes are adsorbed onto glass fiber filters. Receptor sites, both empty and occupied by endogenous hormone, are labelled by incubation with 20 nM [3H]estradiol without (total binding) or with 2 microM radioinert estradiol (nonspecific binding). Buffer containing unbound radioactive estradiol is then drained, the filters washed, transferred into vials and counted in toluene-based scintillator. Following removal from the scintillator, DNA content of the filters can be measured by the Burton procedure. This exchange technique is easy and specific, with accuracy and precision similar to those of the technique of Bayard et al. (Bayard, F., Damilano, S., Robel, P. and Baulieu, E.E. (1978) J.Clin. Endocrinol. Metab. 46, 635-648). It offers the advantage of increased sensitivity, allowing receptor determinations on nuclear samples containing more than 10 microgram DNA. Approximately 20 measurements can be made from 50 mg tissue (wet weight).

Cell Nucleus↗
PubMed1980

Estradiol and progesterone receptors in human endometrium: normal and abnormal menstrual cycles and early pregnancy.

Estradiol and progesterone receptor sites (empty or filled with endogenous hormone)have been measured in the cytoplasm and nuclei of human endometrium. Receptor changes have been observed throughout the normal menstrual cycle. During the preovulatory phase the cytoplasmic estradiol receptor sites do not change while the nuclear receptor sites more than double. Cytoplasmic estradiol receptor sites decrease very early in the secretory phase, whereas the decrease in nuclear sites occurs later. Cytoplasmic progesterone receptor sites more than double during the preovulatory phase and show a large decrease immediately after ovulation, when the concentration of nuclear receptor is at its highest. Thus the total cellular concentrations of both estradiol and progesterone receptors are lowest in the late secretory phase. It was found that they are positively correlated with the concentration of plasma estradiol only during the proliferative phase. The concentration of cytoplasmic progesterone receptor is negatively correlated with 17 beta-hydroxysteroid oxidoreductase activity during the secretory phase. In anovulatory cycles the concentrations of estradiol and progesterone receptors are high, similar to those of the late proliferative phase. "luteal insufficiency" is characterized by a very low concentration of estradiol receptor. Early pregnancy endometrium (8 to 10 weeks' gestation) is characterized by a large concentration of progesterone receptor, exceeding those of any period of the menstrual cycle.

Anovulation↗
PubMed1980

Unoccupied nuclear oestradiol-receptor sites in normal human endometrium.

The existence of unoccupied nuclear oestradiol-receptor sites in normal human endometrium was investigated. Nuclei were prepared from endometrial samples obtained by curettage and exposed to [3H]oestradiol, which became maximmaly bound at 0 degrees C within 1 h. This result contrasted with the binding kinetics of oestradiol--receptor complexes, since the exchange of hormone took at least 3 h at 30 degrees C and no displacement occurred at 0 degrees C. Before concluding that the nuclear sites were unoccupied, the presence of endogenous low-affinity ligands was excluded, because the association rate of oestradiol was unchanged after nuclei were stripped from their putative ligands, and the displacement of oestrone bound to nuclear receptor by oestradiol was very slow at 0 degrees C. The available sites had high affinity for oestradiol (KD 1.3 nM) and binding-specificity characteristics of oestradiol receptors. Similar results were observed with crude and purified nuclear preparations. It was concluded that a significant proportion of nuclear oestradiol receptors in normal human endometrium is unoccupied by endogenous hormones.

Cell Nucleus↗
PubMed1979

Glucocorticoid receptor in human embryo fibroblasts. I. Kinetic and physicochemical properties.

The kinetics of dexamethasone binding to L 809 E cell line cytosol have been investigated by means of the protamine sulfate precipitation assay. The KDeq for dexamethasone was 1.1--3.3 nM. Binding was specific for glucocorticoids. The mean association rate constant (k+1) was 8.5 x 10(5) M-1 x min-1 and the dissociation rate constant was 4.6 x 10(-5) min-1 at 0 degrees C. The concentration of binding sites was 0.3 pmol/mg of cytosol protein. Binding kinetics were compatible with a model of positive cooperativity. The receptor sedimented at 7.5--9 S in glycerol gradients. By a combination of calibrated ultracentrifugation and polyacrylamide gel electrophoresis, a Stokes radius of 8.5 nm, a molecular weight of 268 000 daltons and a frictional ratio of 1.8 were determined in low ionic strength conditions. When the cells were incubated with 10 nM [3H]dexamethasone for 1 h, a more than 90% depletion of cytosol receptor and an equivalent accumulation of nuclear dexamethasone--receptor complexes was observed.

Cell Line↗
PubMed1979

Relationships among placental, uterine, and circulating concentrations of progesterone and fetal survival in the ovariectomized pregnant rat.

Pregnant rats were ovariectomized or sham operated on day 15 postcoitum. Four days later, progesterone was measured by RIA in peripheral and uterine vein plasma, in uteri, and in placentae. Maintenance of pregnancy was not critically affected by ovariectomy, since fetal survival was 65.7 +/- 5.1% (mean +/- SEM) despite a large decrease of peripheral plasma progesterone from 115.7 +/- 3.4 to 9.3 +/- 0.5 ng/ml. Peripheral and uterine vein plasma progesterone (8.3 +/- 0.9 ng/ml) were identical. In contrast, placental progesterone decreased only slightly, although significantly, from 27.3 +/- 1.3 to 20.3 +/- 1.0 ng/mg. The concentrations of uterine progesterone were variable and positively correlated with the concentrations of peripheral plasma progesterone. It was concluded that uterine progesterone originates from peripheral blood but not from placentae and that fetal survival is positively correlated with residual progesterone concentrations in peripheral plasma and in uterus but not in placentae.

Animals↗
PubMed1979

[Luteal insufficiency. Histoclinical and biological correlations].

Luteal insufficiency, an entity accepted with difficulty, is responsible for 3.5 p. 100 of cases of infertility and 35 p. 100 of early abortions. This study, carried out in 328 women with an average age of 29 years, involved clinical and histological features, as well as the estimation of plasma levels and endometrial receptors of ovarian steroids. Three broad histological patterns emerged:--luteal insufficiency associated with oestrogenic insufficiency indicative of overall ovarian deficiency;--luteal insufficiency with functional dysmaturation indicative of deficient or delayed luteal function, with or without persistence of excessively high oestrogen activity,--luteal insufficiency related to the short life of the corpus luteum which stops on the 20th day. Relationships between histological findings, the measurement of receptors and plasma estimations are discussed and precise analysis of endometrial biopsies must be considered as one of the best test of luteal insufficiency.

Adult↗
PubMed1978

[Response to an antiestrogen as a criterion for hormonal sensitivity of endometrial cancer].

A test is described for the evaluation of hormone sensitivity of endometrial cancer in vivo. The concentrations of progesterone and estradiol receptors, and the activities of ornithine-decarboxylase and 17 beta-hydroxysteroid oxido-reductase enzymes have been measured in the tumor, before and after administration of the anti-estrogen tamoxifen. The responses observed, in particular the increase of progesterone receptor, could allow a more rational approach to hormonal therapy of endometrial cancer.

17-Hydroxysteroid Dehydrogenases↗