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R Mornex

Publications and source records attributed to R Mornex.

At least 73 records · Page 4Linked to original sources
PubMed1984

Regulation of somatostatin secretion in man: study of the role of free fatty acids and ketone bodies.

We have investigated in normal subjects the possible role of plasma free fatty acids (FFA) and blood ketone bodies (KB) in the regulation of human somatostatin secretion. Heparin injected during the intravenous infusion of a fat emulsion raised FFA levels acutely from 0.4 +/- 0.1 to near 3 mmol/L. Plasma somatostatin-like immunoreactivity (SLI) rose from a mean (+/- SEM) basal value of 9.2 +/- 1.0 ng Eq S14/L to 20.0 +/- 6.0 ng Eq S14/L (P less than 0.05). Plasma immunoreactive insulin (IRI) level was unchanged and glucagon (IRG) concentration decreased from 156 +/- 20 to 107 +/- 2 ng/L (P less than 0.05). During this test, there was a rise not only in FFA but also in plasma triglycerides (TG) and in blood glycerol and KB levels. The infusion of a fat emulsion alone increased triglyceride and glycerol levels to a similar extent but induced also a mild rise of FFA (0.37 +/- 0.05 to 1.13 +/- 0.5 mmol/L, P less than 0.01), KB (78 +/- 12 to 360 +/- 45 mumol/L, P less than 0.01), and SLI (14.8 +/- 4.6 to 23.8 +/- 7.1 ng Eq S14/L, P less than 0.05). The induction by DL-Na-3-hydroxybutyrate infusion of a rise of KB was associated with a decrease of FFA (P less than 0.05) and SLI (P less than 0.05) without modification of IRI or IRG levels. Phentolamine infusion did not modify the SLI or glucagon response to acute elevations of FFA, whereas propranolol suppressed the increase of SLI without preventing the concomitant decrease of IRG.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1984

Glucose metabolism in experimental hyperthyroidism: intact in vivo sensitivity to insulin with abnormal binding and increased glucose turnover.

The characteristics of the dose response of insulin on the glucose turnover rate and erythrocyte insulin binding parameters were determined in five normal men before and during experimentally induced hyperthyroidism [L-T4 (2 micrograms kg-1 day-1) for 4 weeks with additional L-T3 (1 microgram kg-1 day-1) for the following 3 weeks]. Hyperthyroidism was characterized by significant rises in T3 from 1.92 +/- 0.17 (+/- SEM) to 3.66 +/- 0.17 nmol/liter (P less than 0.01) and resting metabolic rate from 39 +/- 0.7 to 48 +/- 1 watt/m2 (P less than 0.001). While the subjects received a diet adapted to the metabolic rate, blood glucose rose from 3.8 +/- 0.07 to 4.46 +/- 0.11 mmol/liter (P less than 0.05) without a significant change in plasma insulin. During the insulin dose-response study, glucose infusion rates were unaltered by hyperthyroidism, and neither the maximum effect nor the sensitivity to insulin was altered. Glucose turnover rate, measured using [6,6-2H2]glucose as tracer, was determined in the basal state and during the 0.4 mU kg-1 min-1 insulin infusion. In the basal state, it was significantly increased by hyperthyroidism (control, 2.3 +/- 0.1; hyperthyroidism, 3.7 +/- 0.1 mg kg-1 min-1). During the insulin infusion, hepatic glucose production was totally suppressed before T4 and T3 treatment, but was 0.96 +/- 0.39 mg kg-1 min-1 during T4 and T3 treatment. A marked decrease in the insulin binding affinity to erythrocytes was found without a change in the insulin receptor number. In conclusion, glucose metabolism in experimental hyperthyroidism is characterized by 1) increases in basal glucose production and utilization; 2) antagonism between the effect of insulin and hyperthyroidism at the hepatic level; and 3) lack of peripheral insulin resistance in spite of marked alteration in erythrocyte insulin binding affinity.

Adult↗
PubMed1983

[Measurement of insulin sensitivity using the somatostatin-insulin-glucose test. Importance of the determination of plasma free fatty acids and insulin clearance].

Insulin sensitivity was determined in normal subjects and in subjects with possible insulin-resistance by simultaneous infusion of somatostatin, insulin and glucose. C peptide, growth hormone and glucagon were decreased by somatostatin in all subjects. Steady-state blood glucose was 2.84 mM (mean) in normal subjects and between 11 and 15 mM in the other subjects (p less than 0.01), indicating severe insulin resistance. Steady state plasma insulin was 50 mU/l (mean) in control subjects, but was markedly lower in one of the subjects with insulin-resistance and higher in the other two subjects, suggesting abnormalities in insulin clearance in these subjects. An index of insulin sensitivity taking into account these variable insulin levels was decreased in the insulin-resistant subjects (21 to 61, vs 117 to 251; p less than 0.01). Insulin-resistant subjects had increased basal levels of plasma free fatty acids (p less than 0.01) which failed to decrease during the test as in control subjects, suggesting abnormal metabolic regulation. In contrast, blood ketone bodies were normal in the basal state and decreased similarly in all subjects during the test, suggesting that hepatic ketogenesis does not resist to insulin.

Adult↗
PubMed1983

[Detection of thyrostimulating immunoglobulins in whole serum. Value of the culture of human thyroid cells].

TSAb was assayed in whole serum using a human thyroid cell culture system. Sera (20.% final concentration) were added to each well (10(6) cells) at the initiation of the culture. After 48 h of incubation, total AMPc was assayed and results, when significantly different, were expressed as per cent of basal values. Among 67 untreated patients with Graves' disease, TSAb was detected in 64 (95.5%), with activity varying from 135 to 1000%. No correlation was found between TSAb activity and clinical presentation or thyroid hormones levels. None of the 7 patients with Hashimoto's thyroiditis, or of the 12 with simple goiter or of the 25 normal subjects tested was positive. One of the 10 patients with proven toxic adenoma was weakly positive. When compared under the same conditions, activities of whole sera or of corresponding ammonium sulfate precipitates were similar. Reproducibility averaged 15% and 25% within an assay and between assays respectively. Prolongation of incubations for 48 h instead of 2 h markedly increased the sensitivity of TSAb detection. This culture system provides a relatively simple, sensitive and reliable bioassay for TSAb.

Adolescent↗
PubMed1983

Role of GABA in the control of thyrotropin secretion in the rat.

Various doses of GABA from 0.25 to 5 mumol injected into the third ventricle decrease serum TSH rapidly. The same effect was observed with GABOB (10 mumol), the hydroxylated form of GABA. The inhibitory effect of both of these drugs was prevented by picrotoxin injection (1 microgram). Peripheral injection of GABAergic drugs such as GABOB or AOAA also decreased serum TSH. In vitro, the addition of GABA (from 6.7 . 10(-6) to 6.7 . 10(-4) M) to the incubation medium of hemi-anterior pituitary did not modify the liberation of TSH. To test the physiological role of GABA in the regulation of thyrotropin function the circadian TSH rhythm was used as a model. Both GABAergic inhibitors, picrotoxin (10 microgram/kg b.w.) as well as semicarbazide (150 mg/kg b.w.), induced an increase of the low basal nocturnal level of TSH (centered on the 02.00 h time point) without altering the diurnal peak of TSH. We conclude that GABA has an inhibitory effect on central thyrotropin control via an inhibition of TRH release from the hypothalamus and might be, at least partly, responsible for the low nocturnal levels of serum TSH observed during the circadian physiological rhythm.

Animals↗
PubMed1983

Purification and characterization of a phosvitin kinase from the thyroid gland.

1. Two cyclic AMP independent protein kinases phosphorylating preferentially acidic substrates have been identified in soluble extract from human, rat and pig thyroid glands. Both enzymes were retained on DEAE-cellulose. The first enzyme activity eluted between 60 and 100 mM phosphate (depending on the species), phosphorylated both casein and phosvitin and was retained on phosphocellulose; this enzyme likely corresponds to a casein kinase already described in many tissues. The second enzyme activity eluted from DEAE-cellulose at phosphate concentrations higher than 300 mM, phosphorylated only phosvitin and was not retained on phosphocellulose. These enzymes were neither stimulated by cyclic AMP, cyclic GMP and calcium, nor inhibited by the inhibitor of the cyclic AMP dependent protein kinases. 2. The second enzyme activity was purified from pig thyroid gland by the association of affinity chromatography on insolubilized phosvitin and DEAE-cellulose chromatography. Its specific activity was increased by 8400. 3. The purified enzyme (phosvitin kinase) was analyzed for biochemical and enzymatic properties. Phosvitin kinase phosphorylated phosvitin with an apparent Km of 100 micrograms/ml; casein, histone, protamine and bovine serum albumin were not phosphorylated. The enzyme utilized ATP as well as GTP as phosphate donor with an apparent Km of 25 and 28 microM, respectively. It had an absolute requirement for Mg2+ with a maximal activity at 4 mM and exhibited an optimal activity at pH 7.0. The molecular weight of the native enzyme was 110 000 as determined by Sephacryl S300 gel filtration. The analysis by SDS-polyacrylamide gel electrophoresis revealed a major band with a molecular weight of 35000 suggesting a polymeric structure of the enzyme.

Animals↗
PubMed1983

Circannual variations of TSH circadian rhythm parameters in the rat.

We had previously observed a circadian rhythm for serum TSH in male Sprague-Dawley rats (under a 12-hour light-dark cycle, light off at 19.00 h). In the present work the parameters of this previously observed TSH rhythm were determined over a year on a monthly basis. A circadian rhythm was detected for each month except April. From month to month, the amplitudes and acrophases of these rhythms were not significantly different, and a circannual rhythm was only established for the mean TSH concentration over the 24-hour period (mean hormonal value). We conclude that there is a constant circadian pattern for serum TSH fluctuations superimposed on a small basal circannual rhythm of the mean hormonal value.

Animals↗
PubMed1983

Control of thyrotropin glycosylation in normal rat pituitary cells in culture: effect of thyrotropin-releasing hormone.

Regulation of glycosylation of TSH was studied in primary cultures of normal rat pituitary cells. [3H]Glucosamine or [3H]proline incorporation into immunoprecipitable TSH and trichloroacetic acid-precipitable proteins was measured after incubation periods ranging from 4-72 h. TSH release was assessed by RIA of TSH in the medium. TRH (30 nM) specifically increased the glycosylation of TSH despite the fact that it did not stimulate [3H]proline incorporation into the hormone even after 72 h of continuous labeling. The TRH-stimulated [3H]glucosamine-labeled TSH was completely recovered in the incubation medium. Effective concentrations of TRH were in the same range as those necessary for stimulation of TSH release (10(-10) - 10(-6) M). Somatostatin (50 nM) and T3 (10 microM) antagonized TRH effects on both TSH release and glycosylation. Stages of TSH glycosylation were discriminated by the addition to the culture medium of tunicamycin (10 micrograms/ml) or monensin (25 microM), which are known to inhibit core and terminal glycosylation of proteins, respectively. Medium [3H]glucosamine-labeled TSH was fully glycosylated, whereas a large part of the intracellular hormone was only core glycosylated. This suggests that terminal glycosylation of TSH could be related to hormone secretion. TRH stimulated essentially only terminal glycosylation of TSH. No alteration of core glycosylation of the hormone was observed after TRH treatment. The stimulating effect of TRH on terminal glycosylation of TSH is probably related to its ability to stimulate hormone release.

Animals↗
PubMed1983

Hormonal and metabolic effects of near physiological increase of plasma immunoreactive somatostatin 14.

The possibility that somatostatin 14 (SRIF) may exert true endocrine actions in man was tested by investigating the hormonal and metabolic effects of the peptide infused for 80 min at rates of 36.5, 73, and 146 pmol kg-1 h-1 in six healthy subjects who fasted overnight. These three doses increased the level of plasma SRIF-like immunoreactivity in the range of concentrations recorded postprandially with the same assay system. These low SRIF infusion rates decreased insulinemia and to a lesser extent glucagonemia, and increased glucosemia and ketonemia. Both the reduction of insulin and the increase of glucosemia were significantly related to the increase of plasma SRIF-like immunoreactivity. All parameters returned to control values upon discontinuing the peptide infusion. This study suggests that SRIF may have an endocrine role in man and that such low dose, short time SRIF infusions could exert metabolic effects different from those of larger, probably pharmacological, infusion rates.

Adult↗
PubMed1983

Role of catecholamines in the ketonemic response to somatostatin in normal man.

In order to determine if a rise of circulating catecholamines occurs during somatostatin (SRIF) infusion in normal man, and if this increase plays a significant metabolic role, we infused four normal subjects with SRIF (500 micrograms/h) alone or associated with either alpha-(phentolamine) or beta-(propranolol) adrenergic blocking agents. During SRIF infusion, the initial small decrease in blood glucose was followed by a rise of epinephrine from 25-46 ng/liter (range) to 117-143 ng/liter (range) (P less than 0.05) at 80 min and norepinephrine from 204 +/- 16 to 418 +/- 60 ng/liter at 90 min (P less than 0.05). Thereafter, plasma nonesterified fatty acids, blood glycerol, and ketone bodies increased significantly. Phentolamine adjunction modified neither the catecholamines rise, nor the metabolic changes. Propranolol adjunction did not modify the glucose fall and the catecholamine rise, but resulted in blunted increments of fatty acids and glycerol and in an almost complete suppression of the increase of ketone bodies. These results suggest that the enhanced lipolysis and ketogenesis observed during SRIF infusion are not only due to the SRIF-induced insulin deficiency but also in part to a beta-receptor mediated effect of catecholamines.

Adult↗
PubMed1983

Regulation of ketonaemia in hyperthyroidism: study of the role of free fatty acids.

We have indirectly assessed the role of free fatty acids (FFA) and of hepatic ketogenesis in the regulation of ketone body levels in euthyroid and hyperthyroid subjects. All studies were performed under controlled dietary conditions (35 and 45 kcal/kg body weight/day respectively for euthyroid and hyperthyroid subjects). In the post-absorptive state hyperthyroid patients had normal, glucagon levels and, in spite of increased insulinemia (p less than 0.02), elevated concentrations of blood glucose (p less than 0.01), glycerol (p less than 0.001) and ketone bodies (p less than 0.05). In the face of this hyperketonaemia, there was no significant increase of plasma FFA, suggesting possible increased hepatic conversion of FFA to ketone bodies. However, when FFA were acutely raised to high levels, the induced rise of ketone bodies was similar in hyperthyroid and euthyroid subjects. Oral propranolol administration to hyperthyroid patients in the post-absorptive state decreased the concentrations of glycerol (p less than 0.05) and ketone bodies (p less than 0.05) without altering insulin concentrations. Ketone bodies fell without any significant decrease of FFA suggesting a possible direct effect of propranolol administration on hepatic ketogenesis. However, the ketone body response to raised FFA levels was unaffected by propranolol. We have evidence in hyperthyroid patients of increased lipolysis and ketogenesis in spite of increased daily caloric intake. These results suggest that these metabolic abnormalities are not merely due to relative starvation. We have tentative evidence for modification of the intra-hepatic conversion of FFA to ketone bodies in the post-absorptive state but no supporting evidence when FFA levels were experimentally raised.

Adult↗
PubMed1983

[Dopaminergic agents in the treatment of hyperprolactinemia].

The treatment of hyperprolactinemia with dopaminergic agents is directly correlated with the improvement of the knowledge about hypothalamic control of prolactin secretion. Since 1963 it is wellknown that the hypothalamus acts on this activity of the pituitary gland with a tonic inhibition. A prolactin inhibiting factor (PIF) was suspected for this control and the tubero-infundibular dopaminergic system was considered to modulate the secretion of PIF. In fact a lot of experience demonstrated a direct control of dopamine on pituitary gland itself (fig. 1). Ergot alkaloids are the most useful dopaminergic drugs. They derive from 6 methyl 9 ergoline (fig. 2) and, in the main group of 12 ergocryptine molecules, alpha-ergocryptine and ergocornine are the most potent (fig. 3). Bromocryptine (2 alpha-bromoergocryptine, BEC) is a compound (fig. 4) with a magnification of the effect on prolactin secretion and loss of uterotonic and vasoconstrictive effects. This drug acts directly on normal pituitary cells and on adenomas in vitro. The inhibition of secretion is first seen, followed by inhibition of synthesis. Transplanted tumors (MtTW15) are sensible to ergocornine but not to BEC. The oral administration of the drug is followed by an increase in serum concentration (fig. 5) maximum at 3 hours. The decrease of prolactin is progressive and prolonged until the 7th hour. Some similarities between the structure of dopamine and bromocryptine may explain the effect of the drug (fig. 6). Hyperprolactinemia constitutes a frequent clinical syndrome with amenorrhea-galactorrhea and sterility. The cause is a pituitary tumor composed of prolactin secreting cells. All the clinical and biological manifestations are due to high prolactin secretion and the surgical ablation of the adenoma is followed by complete cure. This result is obtained frequently in microadenomas. The medical treatment of hyperprolactinemia with BEC was initiated in 71 by Lutterbeck. Since that time a lot of clinical experiences give the same kind of results: Improvement in 100% of galactorrhea, 90% of amenorrhea and 80% of fertility. These results are now wellknown and the secondary effects of the drug are quite limited. The development of pregnancy in a patient suspected of a pituitary adenoma is a major problem which is now clearly solved. In a survey of the literature Nillius found 146 patients in this situation with only 5.6% of complication. Our experience with 18 patients is confirmative. Moreover we found after delivery a decrease of serum prolactin (fig. 7).(ABSTRACT TRUNCATED AT 400 WORDS)

Bromocriptine↗
PubMed1983

[Medical treatment of pheochromocytoma].

Medical treatment of pheochromocytoma is only conceivable in the context of preparing the patient for surgery or in the rare cases of inoperable tumour. Only peripheral catecholamine inhibitors should be used (alpha- or betablockers). Treatment should always start with alphablockers. The results obtained are difficult to analyse and it is not possible to lay down systematic doctrine, the indication being considered case by case.

Adrenal Gland Neoplasms↗
PubMed1983

Anti-tubulin antibodies in autoimmune thyroid disorders.

The presence of circulating antibodies directed against a cytoskeletal element, microtubules, in patients with autoimmune thyroid disorders, has been studied using pure brain tubulin as antigen. Immune complexes were immunoprecipitated using a goat anti-human immunoglobulin antibody. Twenty sera among 48 (41%) from patients with Graves' disease and nine sera among 16 (56%) from patients with Hashimoto's thyroiditis had increased levels of anti-tubulin antibodies as compared to that of 26 sera from control subjects. Only one serum among 11 from patients with toxic adenoma was positive. Very similar results were obtained using protein A adsorbent to collect immune complexes. Specificity of the tubulin binding activity was ascertained by dilution of the sera and displacement of tracer tubulin by unlabelled pure tubulin from rat or human brain. Anti-tubulin antibody titres were variable; one serum was positive at dilution higher than 1:15,000, a titre similar to those obtained in animals experimentally immunized against tubulin. Binding of labelled and unlabelled tubulin to immunoglobulins from positive sera was strictly competitive. The apparent affinity constant for the binding of tubulin to human anti-tubulin autoantibodies determined on four sera was 0.2-0.6 X 10(9)/M. There was no significant association between anti-tubulin antibodies and anti-microsomal antibodies or anti-thyroglobulin antibodies or thyroid stimulating antibodies. In contrast, only five to six per cent of sera from patients with other autoimmune diseases: lupus erythematosis or pernicious anaemia, had increased levels of anti-tubulin antibodies. In conclusion, tubulin represents a new autoantigen which is expressed rather specifically in autoimmune thyroid disorders and probably independently from the classical thyroid antigens.

Adult↗
PubMed1982

Evidence for a coupling of prolactin secretion and synthesis by rat pituitary cells in culture.

The relationship between the release and the synthesis of prolactin by rat pituitary cells in culture was studied using a microtubule-disrupting drug, vinblastine. (1) Prolactin secretion was inhibited by vinblastine in short-term incubations. Vinblastine did not act via the dopamine pathway, since a potent anti-dopaminergic drug, fluphenazine, was unable to reverse the inhibiting action of the antimicrotubular agent. (2) Continuous treatment by vinblastine induced a progressive decrease of the rate of incorporation of [3H]leucine in prolactin. The half-inhibition time was about 2 days. This inhibition of prolactin synthesis was selective, since total protein synthesis remained unaffected. (3) Measurements of radioimmunoassayable prolactin showed that the inhibition of hormone release by vinblastine led to a transient increase of the intracellular content of prolactin. The phase of over-accumulation was followed by a progressive reduction of the total (cell + medium) prolactin. This result is in agreement with the observed inhibition of de novo synthesis of prolactin and indicates that a degradation process takes place in pituitary cells in culture. In conclusion, the use of vinblastine allows us to demonstrate that the rate of prolactin synthesis is dependent upon the secretory status of the cell.

Animals↗