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Biomedical subjects

M Vincens

Publications and source records attributed to M Vincens.

At least 19 recordsLinked to original sources
PubMed2001

Treatment with dehydroepiandrosterone sulfate increases NMDA receptors in hippocampus and cortex.

Our aim was to investigate if the memory-enhancing effects reported for dehydroepiandrosterone sulfate in rodents could be mediated through modulation of NMDA receptors. Using autoradiography we studied the effect of dehydroepiandrosterone sulfate, administered for 5 days (30 mg/kg, i.p. twice a day), on NMDA binding sites labelled with [3H]dizocilpine ([3H]MK801) in rat brain. Dehydroepiandrosterone sulfate treatment significantly increased the [3H]MK801 binding sites in hippocampal areas (field CA1, CA3, dentate gyrus lateral blade and medial blade) and in cortex layer IV as compared to the control group. These results demonstrate for the first time the ability of dehydroepiandrosterone sulfate to increase the number of NMDA binding sites in rat brain, an action that could be of interest for therapeutic application.

Animals↗
PubMed1998

A novel recognition site for somatostatin-14 on the GABA(A) receptor complex.

Functional interactions between gamma-aminobutyric acid (GABA) and somatostatin are suggested by the presence of synaptic contacts between GABA and somatostatin neurons, colocalisation of GABA and somatostatin and reciprocal modulation of somatostatin and GABA release. Nevertheless, a direct interaction of somatostatin with the GABA(A) receptor complex has not yet been investigated. A quantitative autoradiographic technique was used to determine the ability of somatostatin to interact with the [35S]t-butylbicyclophosphothionate [35S]TBPS binding sites of the GABA(A) receptor complex: somatostatin inhibited [35S]TBPS binding with IC50 values in the micromolar range in all brain regions studied. These results demonstrate for the first time a direct interaction between somatostatin and the GABA(A) receptor complex.

Animals↗
PubMed1995

An autoradiographic study comparing the interactions of 3 alpha-OH-5 alpha-pregnan-20-one, pregnenolone sulfate and pentobarbital with [3S]-TBPS binding sites and their modulation by GABA in different structures of the rat brain.

Using quantitative autoradiography, we have studied the distribution of the [35S]-TBPS binding sites of the GABA-A receptor complex in various structures of the rat brain. High densities of binding sites were observed in layer IV of the cerebral cortex, in the globus pallidus, and in the thalamus. Intermediate densities of binding sites were observed in superficial and deep layers of the cerebral cortex, in the dentate gyrus and in the hippocampus. For all of these structures, the interactions of 3 alpha-OH-5 alpha-pregnan-20-one (3 alpha 5 alpha P), pregnenolone sulfate (PS), and pentobarbital with [35S]-TBPS binding, in the presence or the absence of GABA were studied. In the absence of GABA, IC50 values for the inhibition of [35S]-TBPS binding were 10(-6) M for 3 alpha 5 alpha P and 10(-4) M for PS and pentobarbital in all of the brain regions studied. In the presence of GABA (5 x 10(-6) M), IC50 values were decreased by one order of magnitude for 3 alpha 5 alpha P, PS, and pentobarbital in all structures studied except layer IV of the cortex, where the IC50 value for PS was more markedly decreased (up to two orders of magnitude). By contrast, IC50 values for picrotoxin and TBPS to inhibit [35S]-TBPS binding were 10(-7) M and 10(-8) M, respectively, in the presence or absence of GABA.

Animals↗
PubMed1994

Inhibitory effect of 5 beta-pregnan-3 alpha-o1-20-one on gonadotropin-releasing hormone gene expression in the male rat.

Neuroanatomical data have documented the existence of synaptic contacts between gamma-aminobutyric acid (GABA) terminals and preoptic gonadotropin-releasing hormone (GnRH) neurons in the rat anterior hypothalamus. In addition, pharmacological studies have suggested that the GABAergic system may be involved in the control of gonadotropin release. Moreover, it has been shown that some progesterone metabolites such as 5 beta-pregnan-3 alpha-ol-20-one (5 beta 3 alpha P) are able to interact with the GABAA receptor complex. In the present study, we have investigated the effects of chronic (5 days) treatment with the GABAA-positive ligand 5 beta 3 alpha P (20 mg/kg body weight i.p., twice a day) or with the GABAA agonist muscimol (1 mg/kg body weight i.p., twice a day) alone or in combination on GnRH mRNA levels in the preoptic area of the male anterior hypothalamus as measured by in situ hybridization. Treatment with 5 beta 3 alpha P produced a 30% decrease in the number of grains overlying labelled cells, while muscimol treatment decreased the hybridization signal by 36%. The concomitant administration of 5 beta 3 alpha P and muscimol resulted in a 46% decrease in the GnRH mRNA levels. This inhibitory effect was completely antagonized by the concomitant administration of picrotoxin (4 mg/kg body weight i.p., twice a day). These data suggest that the GABAA receptor complex and steroids that interact positively with this GABAA receptor complex may play an important role in the regulation of GnRH biosynthesis by hypothalamic neurons.

Animals↗
PubMed1993

Autoradiographic study of neurosteroid binding sites labelled with [35S]-TBPS in brain of different species.

Distribution of [35S]-TBPS binding sites was studied in various structures of brain in mouse and guinea pig and in cortex of monkey and in hippocampus of postmortem human brain. As it is observed for rat brain, high densities of [35S]-TBPS binding sites were found in layer IV of cortex in the four species, and in thalamus of mouse and guinea pig. Intermediate densities of binding sites were observed in superficial and deep layers of cortex in those four species and in hippocampus of mouse, guinea pig, and human. In all brain structures studied, 5 alpha 3 alpha P and picrotoxin produced a dose-dependent inhibition of [35S]-TBPS binding. No significant interregion or interspecies differences could not be detected for IC50 values of 5 alpha 3 alpha P or picrotoxin to inhibit [35S]-TBPS from its binding sites. In all regions studied, IC50 values were close to 1.5 x 10(-6) M for 5 alpha 3 alpha P and 2.3 x 10(-7) M for picrotoxin.

Animals↗
PubMed1992

Comparison between the interaction of steroids with [35S]TBPS binding to cerebral cortical and to pituitary membranes: correlation with inhibition of prolactin release.

It has been shown previously that 5 alpha-pregnan-3 alpha-ol-20-one (5 alpha 3 alpha P) can inhibit prolactin release from anterior pituitary gland cells in culture through an interaction with a specific modulatory site on the GABAA receptor complex in anterior pituitary gland membranes. In the present work, this receptor site has been labelled with [35S]t-butylbicyclophosphorothionate ([35S]TBPS) to enable a study of the relative binding affinities (RBA) of different steroids for the GABAA receptor complex to be made. We have found a high correlation (r = +0.88) between the inhibition of [35S]TBPS binding to anterior pituitary membranes and the inhibition of [35S]TBPS binding to cerebral cortical membranes by nine different steroids. There was also a high correlation between the inhibition of prolactin release from anterior pituitary gland cells in culture by these steroids and the inhibition of [35S]TBPS binding to anterior pituitary membranes (r = +0.99) or to cortical membranes (r = +0.81). These observations suggest that the measurement of prolactin release from anterior pituitary gland cells in culture is a good indicator of the functional activity of drugs that bind to the allosteric modulatory TBPS-binding site on the GABAA-receptor complex.

Animals↗
PubMed1991

Pituitary enlargement with suprasellar extension in functional hyperprolactinemia due to lactotroph hyperplasia: a pseudotumoral disease.

Beside the well characterized PRL-secreting adenomas, a wide spectrum of functional hyperprolactinemic states exists. We describe here five women, 21-38 yr old, all suspected of having a PRL-secreting adenoma because of a pseudotumoral appearance of the pituitary on computerized tomographic (CT) scan or magnetic resonance imaging (MRI). Four had oligomenorrhea with or without galactorrhea, one had amenorrhea with galactorrhea, and two complained of infertility. In the same patient, basal plasma PRL levels were variable on different days, sometimes normal (mean +/- SEM, 11.3 +/- 1.5 micrograms/L), sometimes elevated (49 +/- 7 micrograms/L), but in all cases, a PRL response of large amplitude to TRH (6- to 8-fold increase in the basal value) was observed. Basal plasma levels of estradiol were within luteal phase normal values (0.41 +/- 0.13 pmol/L), while progesterone levels were low (1.92 +/- 0.47 nmol/L). CT scan or MRI showed an intrasellar mass with suprasellar extension, suggesting a tumoral process. However, the signal intensity was homogeneous, and on coronal views, the suprasellar extension was pyramidal and symmetrical, and the pituitary stalk was always in the midline. The five patients were operated on by the transsphenoidal route, but no adenoma was found. Surgical biopsies were taken in four cases, and lactotroph hyperplasia, i.e. enlarged cell cords consisting mainly of PRL cells, was found in three of them. One case displayed a continuum between areas of lactotroph hyperplasia and adenomatous PRL cells. We conclude that functional hyperprolactinemia may mimic on CT scan or MRI a PRL-secreting adenoma.

Adult↗
PubMed1989

A progesterone metabolite enhances the activity of the GABAA receptor complex at the pituitary level.

The interaction of 5 alpha-pregnane-3 alpha-ol-20-one (5 alpha 3 alpha P), a progesterone metabolite, with the GABAA receptor chloride channel complex was investigated at the pituitary level. In nanomolar concentrations this steroid potentiated the inhibitory effect of muscimol (a GABAA agonist) on prolactin release from rat pituitary cells in culture. In micromolar concentrations 5 alpha 3 alpha P had a direct inhibitory effect, similar to that of muscimol, with an IC50 value of 370 nM. This effect was antagonized by bicuculline, a GABAA antagonist, and by picrotoxin, a chloride ion channel blocker. Its reduced isomer, 5 alpha 3 beta P, and progesterone (Pg) were devoid of activity. Using [35S]t-butylbicyclophosphorothionate ([35S]TBPS) as a ligand, we demonstrated, for the first time, specific barbiturate sites on pituitary membranes, similar to those of the central nervous system, with a Kd value of 25 nM and a Bmax value of 62 fmol/mg protein. 5 alpha 3 alpha P inhibited the binding of [35S]TBPS. In contrast, its 3 beta isomer was inactive. These data show that 5 alpha 3 alpha P enhanced the activity of the GABAA receptor complex at the pituitary level and suggest that its inhibitory effect on prolactin release might be mediated by the barbiturate site or by a closely related site.

5-alpha-Dihydroprogesterone↗
PubMed1989

Evidence that clomethiazole interacts with the macromolecular GABA A-receptor complex in the central nervous system and in the anterior pituitary gland.

Clomethiazole (CLOM) is known to be an anticonvulsant drug and has been also reported to decrease serum prolactin (PRL) in humans. Both effects may be mediated by an enhancement of gabaergic transmission. In order to determine if (CLOM) interacts with GABA metabolism and/or at the GABA receptor level, we studied its effect on PRL release and on the binding of various compounds that interact with the GABAA-benzodiazepine-receptor complex. Intraperitoneal (IP) administration of CLOM to rats significantly decreased PRL levels, and this effect was antagonized by IP administration of bicuculline, an antagonist of the GABAA receptor. In vitro, the inhibitory effect of muscimol on PRL release from rat hemiadenohypophysis was potentiated in a dose-dependent manner by preincubation with CLOM. This effect was antagonized by picrotoxin (10(-6) M). On the other hand, CLOM had no effect on GABA metabolism and did not compete with GABAA, GABAB or benzodiazepine binding sites in cortical membranes. CLOM competed, however, with the picrotoxin binding site labelled with [35S]-butylbicyclophosphorothionate (TBPS), at an IC50 value of 1.2 x 10(-4) M, which is in the same range as some barbiturates. These results concerning PRL release and binding experiments with cortical membranes suggest that CLOM interacts with the picrotoxin/barbiturate site of the GABAA-receptor-chloride channel complex.

Animals↗
PubMed1989

Testosterone-estradiol binding globulin (TeBG) in hirsute patients treated with cyproterone acetate (CPA) and percutaneous estradiol.

Testosterone-estradiol binding globulin (TeBG) was studied in 50 hirsute women, before and after 6-month treatment with cyproterone acetate (CPA). 50 mg CPA was administered orally from the 5th to the 25th day of the menstrual cycle and combined with 3 mg 17 beta-estradiol (E2) administered percutaneously from days 16-25 of the cycle. TeBG was evaluated by a filter assay measuring [3H]-DHT binding capacity. Before treatment, the mean plasma TeBG level was 40 +/- 12 nM in hirsute patients, which is significantly lower than TeBG value in normal women (60 +/- 9 nM, n = 20, P less than 0.01) and intermediate between normal women and normal men (30 +/- 8 nM, n = 20). After a 6-month treatment, TeBG strikingly decreased to 22 +/- 8 nM, which is significantly lower than pretreatment values (P less than 0.01) and even less than TeBG level in normal men. Parallel TeBG assay by immunoelectrodiffusion in 8 of these hirsute patients provided similar results. With this treatment, plasma testosterone and delta 4-androstenedione, measured between the 20th and 25th days of the cycle, decreased from 68 +/- 21 to 25 +/- 8 ng/dl, and 210 +/- 95 to 98 +/- 31 ng/dl respectively. Plasma estradiol decreased from 150 +/- 62 pg/ml to 75 +/- 25 pg/ml. In contrast, urinary 3 alpha-androstanediol glucuronide remained high: 112 +/- 51 and 123 +/- 55 micrograms/24 h respectively before and with CPA treatment. Three mechanisms have been proposed to explain TeBG decrease under CPA + E2perc. treatment (1) relative competition of CPA with labelled DHT in the TeBG-binding capacity assay, (2) relative hypoestrogenism with this treatment, (3) a progestagen or even a partial agonistic androgen effect of CPA on TeBG synthesis in the liver. The third mechanism appears to be predominant. In any case. TeBG decrease combined with the partial enzymatic induction effect of CPA on the liver contributes to the increase in the metabolic clearance rate of T and the high urinary Adiol levels previously reported with CPA treatment.

Adolescent↗
PubMed1985

Late-onset adrenal hyperplasia in hirsutism.

We studied the incidence of late-onset adrenal hyperplasia as a cause of hirsutism, its association with the major histocompatibility complex, and its clinical expression. Twenty-four of 400 women seen because of hirsutism were found to have late-onset adrenal hyperplasia, diagnosed on the basis of a high plasma level of 17-hydroxyprogesterone, and its marked increase after ACTH stimulation. The degree of hirsutism varied widely. Plasma antigen levels were high, especially the level of androstenedione, whereas 5 alpha-reductase activity, considered to be a good index of peripheral androgen utilization, showed frequent normal or low values. The 24 patients were genotyped, along with 84 family members, and plasma hormones were measured in the family members. We found a high correlation between late-onset adrenal hyperplasia and HLA antigens B14 and Aw33. Similar biologic profiles were observed in the patients and those of their siblings who were HLA identical (n = 9), confirming that late-onset adrenal hyperplasia is linked to the histocompatibility complex. These nine siblings had no hirsutism. We therefore conclude that the role of skin sensitivity to androgens is important in determining the clinical expression of this disorder.

17-alpha-Hydroxyprogesterone↗
PubMed1985

[Value of the detection of antithyroid antibodies in thyroid pathology].

Antithyroid microsomal hemagglutination antibody (MCHA) and antithyroglobulin hemagglutination antibody (TGHA) were measured in 629 patients with thyroid disease and 100 controls. Thyroid antibodies were present in 4% of control patients, only in women and at low titer. Thyroid antibodies prevalence was 97% in autoimmune thyroiditis (MCHA: 93%; TGHA: 53%), was 55% in Graves disease before treatment (MCHA: 46%; TGHA: 33%) and 90% in the first year following 131I therapy. Antibodies prevalence was 57% in myxoedema (MCHA: 52%; TGHA: 25%). In patients with iodine overload, antibodies prevalence was 29% in euthyroid patients, 25% in iodine-induced hyperthyroidism and 55% in iodine-induced hypothyroidism. Thyroid antibodies detection should be systematically performed in the routine evaluation of any thyroid disorder. Because of discrepancies between TGHA and MCHA positivity, their simultaneous detection should be performed.

Adenoma↗
PubMed1984

Androgen metabolism in hirsute patients treated with cyproterone acetate.

Cyproterone acetate (CPA) in association with percutaneously administered estradiol has been used for the treatment of 150 hirsute patients for periods ranging from 6 months to 3 years. A spectacular clinical improvement ensued. Plasma testosterone (T) and androstenedione (A) fell from 69.0 +/- 24 to 33.0 +/- 8 and 210 +/- 103 to 119 +/- 25 ng/dl (mean +/- SD) respectively after 3 months of treatment and remained low thereafter. In contrast, T glucuronide (TG) and 3 alpha-androstanediol (Adiol) remained high during the whole course of treatment: 37 +/- 9 and 115 +/- 43 micrograms/24 h respectively. In vitro T 5 alpha-reductase activity (5 alpha-R) in pubic skin decreased from 147 +/- 34 to 79 +/- 17 fmol/mg skin after 1 year of treatment. To elucidate the discrepancy between plasma and urinary androgens levels, T production rate (PR) and metabolic clearance rate (MCR) were measured with the constant infusion technique in 7 patients before and after 6 months of treatment. PR decreased from 988 +/- 205 to 380 +/- 140 micrograms/24 h (mean +/- SD). In contrast MCRT increased from 1275 +/- 200 to 1632 +/- 360 1/24 h; this increase in MCRT explains the striking plasma T concentration fall and the high TG and Adiol excretion relative to the decrease in PR. Antipyrine clearance rate (n = 8) increased from 36.3 +/- 5.2 to 51.5 +/- 7.4 ml/min whereas 6 beta hydroxycortisol remained unchanged. In conclusion, CPA acts through several mechanisms: (1) it lowers the androgen input to the target cells by (a) depressing T production through its antigonadotropic effect and (b) accelerating T metabolic inactivation due to a partial enzymatic inducer effect on the liver; (2) at the target cell level it competes with any remaining T for the receptor binding sites; (3) the decrease in the androgen-dependent skin 5 alpha-R is a consequence of both actions of androgen suppression and androgen receptor blockade; it reinforces the antiandrogenic effect of CPA.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1984

Iodine-induced thyrotoxicosis: analysis of eighty-five consecutive cases.

Iodine-induced thyrotoxicosis was documented in eighty-five cases. Eighty per cent occur in apparently normal thyroid glands; 60% among them occur in males. Amiodarone accounted for 50% of iodine-induced thyrotoxicosis. Mean thyroid hormone levels at diagnosis were: FT1: 21.7 (normal mean: 7.5, arbitrary units); T3: 4.53 nmol 1(-1) (normal: 2.30 nmol 1(-1). Mean 131I- 24-h uptake was 3.5% (normal range in France 25-45%) and was activated by exogenous TSH (mean 27%). The spontaneous cure in nontreated cases was observed within an average 6 months. A phase of biological hypothyroidism (mean FT1: 3.7, T3: 1.23 nmol 1(-1), TSH: 9.6 microU ml-1 (normal TSH range: 1-7 microU ml-1] preceded the return to euthyroidism. Intrathyroid iodine content measured by X-ray fluorescence was high, then fell gradually. Thyroid tissue study showed a large quantity of intrathyroid iodine and the overiodination of thyroglobulin. Histological and electron microscopic studies are reported. Prednisone and in some cases propylthiouracile were found to be effective.

Adolescent↗
PubMed1983

[Treatment of hirsutism with cyproterone acetate and percutaneous estradiol].

One-hundred and fifty hirsute women (68 with type I or II polycystic ovary syndrome and 82 with idiopathic hirsutism) were treated for periods of 6 to 48 months with oral cyproterone (CPA), a drug with peripheral antiandrogenic, antigonadotrophic and progestative properties, and 17 beta-estradiol given percutaneously to ensure estrogenic impregnation. CPA was administered in daily doses of 50 mg from day 5 to day 25 of the menstrual cycle, and E 2 (3 mg/day) from day 16 to day 25. The dramatic regression of hirsutism observed after 3 to 6 months of treatment was paralleled by a marked decrease of plasma testosterone and delta 4-androstenedione levels and a decrease of the androgen-dependent skin testosterone 5 alpha-reductase. The CPA-percutaneous E 2 combination also has contraceptive properties. Beside its remarkable therapeutic effectiveness, it has the advantages of avoiding the adverse reactions reported with higher doses of CPA and the metabolic and vascular effects of synthetic estrogen administered orally.

Administration, Oral↗
PubMed1983

[The mechanism of action of cyproterone acetate in the treatment of hirsutism].

Cyproterone acetate (CPA) in association with percutaneously offinistered estradiol has been used for the treatment of 150 hirsute patients for periods ranging from 6 months to 3 years. A spectacular clinical improvement ensued. Plasma testosterone (T) and androstenedione (A) fell from 69 +/- 24 to 33 +/- 8 and 210 +/- 103 to 119 +/- 25 ng/dl (mean +/- SD) respectively after 3 months of treatment and remained low thereafter. In contrast, T glucuronide (Tg) and 3 alpha-androstanediol (Adiol) remained high during the whole course of treatment: 37 +/- 9 and 115 +/- 43 micrograms/24 h respectively. In vitro T 5 alpha-reductase activity (5 alpha-R) in pubic skin decreased from 147 +/- 34 to 79 +/- 17 fmol/mg skin after 1 year of treatment. To elucidate the discrepancy between plasma and urinary androgens levels, T production rate (PR) and metabolic clearance rate (MCR) were measured with the constant infusion technique in 6 patients before and after 6 months of treatment. PR decreased from 988 +/- 205 to 380 +/- 140 micrograms/24 h (mean +/- SD). In contrast MCRT increased from 1275 +/- 200 to 1632 +/- 360 1/24 h; this increase in MCRT explains the striking plasma T concentration fall and the high TG and Adiol excretion relative to the decrease in PR. Antipyrine clearance rate (n = 8) increased from 36.3 +/- 5.2 to 51.5 +/- 7.4 ml/min whereas urinary/6 beta hydroxycortisol remained unchanged. In conclusion, CPA acts through several mechanisms:(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1982

[Virilizing ovarian tumours. Contribution of selective venous catheterization to the diagnosis].

The presence of a virilizing ovarian hilum cell tumours was suspected on account of a rise of plasma testosterone level above 3.5 ng/ml in one patient and a rise of plasma androstenedione level above 3.0 ng/ml in another. The diagnosis was made by selective catheterization of the ovarian and adrenal veins, which showed a high androgen concentration gradient in the vein of the ovary affected as compared with that observed in the adrenal and peripheral veins, and was confirmed by histological examination after ovariectomy. These two cases are contrasted with two other cases with high testosterone plasma levels but without gradient on selective catheterization. One of the patients had abnormal hepatic metabolism (porto-caval shunt) and the other had taken high doses of androgens.

Adrenal Glands↗