Vitamin D and pancreatic islet function. I. Time course for changes in insulin secretion and content during vitamin D deprivation and repletion.

After weaning, rats were given free access to a control or vitamin D-deprived diet for 2 to 5 weeks. In the vitamin D deficient rats, plasma concentrations of 25-(OH)D3, 1,25-(OH)2D3,24,25-(OH)2D3 calcium, glucose and insulin were all decreased. After an overnight fast, the plasma insulin concentration was also decreased even when the plasma glucose concentration was not significantly affected. The food intake and body growth was also impaired in vitamin D-deficient rats. Administration of vitamin D3 in oil for 3 to 6 days to vitamin D-deficient rats increased the plasma concentration of vitamin D metabolites, calcium and insulin, but not that of glucose, and stimulated food intake and body growth to a larger extent than in rats treated by oil alone. Vitamin D deprivation decreased and vitamin D treatment increased the insulin content of the whole pancreas or isolated islets and the secretory response of the islets to D-glucose. The changes in insulin release remained significant when the hormonal output was expressed relative to the insulin content of the islets. These findings confirm that vitamin D deficiency causes alterations of pancreatic B-cell function. Moreover, the time course for changes in biological variables during vitamin D deprivation and treatment suggests that such an alteration cannot be solely accounted for by concomitant abnormalities in either plasma calcium or glucose concentrations.

Comparison of the feedback effect of magnesium and calcium on parathyroid hormone secretion in man.

Administration of high doses of magnesium is known to produce a decrease in parathyroid hormone (PTH) secretion in human patients but the effect of magnesium on the secretion of PTH in healthy man is not known. We have looked at the effect of a relatively moderate i.v. dose of magnesium (7.08 mmol) in seven healthy men. In addition and for comparison the effect of calcium (4.25 mmol) was studied. Two magnesium salts were considered, magnesium sulphate (MgSO4) and magnesium pyrrolidone carboxylate (MgPC). Four i.v. injections were given at 08.00 h (MgPC, NaCl (control), MgSO4 and Ca gluconate), with an interval of 1 week between each injection. Whatever the magnesium salt the variations in plasma concentrations of magnesium were the same whereas no change in erythrocyte magnesium was observed. Plasma concentration of C-terminal PTH did not show significant variations after MgPC or saline injection. Both MgSO4 and Ca gluconate produced a statistically significant 30% decrease in plasma PTH levels 45 min after the injection. The effect was more sustained with calcium (2 h) than with magnesium (45 min). The urinary excretion of magnesium was significantly higher after injection of MgSO4 than after MgPC. These results suggest that magnesium was, on a molar basis, less potent than calcium in regulating PTH secretion in vivo, that the nature of the magnesium salt used must be kept in mind for the interpretation of the effect of magnesium on PTH secretion in vivo and that the decrease in plasma PTH can partly explain the larger urinary excretion of magnesium after MgSO4 than after MgPC.

[Comparison of the secretion of growth hormone during sleep and after pharmacologic stimulation. Results of treatment with hGH in cases of dissociated secretions]. / Comparaison de la sécrétion de l'hormone de croissance au cours du sommeil et après stimulations pharmacologiques. Résultats du traitement par hGH dans les cas de sécrétions dissociées.

Maximal response (peak) of growth hormone (GH) after conventional pharmacologic stimuli have been compared to maximal level reached during sleep in 215 children (123 prepubertal, 92 early pubertal) (group A). A weak correlation (r = 0.37, p less than 0.001) was observed. Five sub-groups of patients could be distinguished according to their GH pharmacologic or sleep peaks: 115 with normal secretion in both cases (I), 10 with complete deficiency (II), 27 with partial deficiency (III), 34 with normal GH sleep secretion and low responses to stimuli (IV) and 29 with the inverse situation (V). A second group (B) of 30 very short children (17 prepubertal and 13 early pubertal) had borderline or variable responses after several pharmacologic stimuli. hGH therapy was done to every patients of sub-group A II, 12 of sub-group A III, 9 of subgroup A IV, 5 of sub-group A V and every one of group B. A sharp rise of growth rate has been obtained with hGH in every patients of sub-groups A II and A III, in 10 out of 14 patients of sub-groups A IV and A V and in almost all patients of group B. A sharp rise of growth rate has been obtained with hGH in every patients of sub-groups A II and A III, in 10 out of 14 patients of sub-groups A IV and A V and in almost all patients of group B. hGH effect in the three last kinds of patients, with atypical GH secretion, was better in those who were in early puberty.(ABSTRACT TRUNCATED AT 250 WORDS)

[Use of hormonal parameters of phospho-calcium metabolism as a means of discriminating bone and joint disorders in patients with renal insufficiency]. / Utilisation des paramètres hormonaux du métabolisme phospho-calcique comme moyen de discrimination des troubles ostéo-articulaires chez les patients insuffisants rénaux.

Serum carboxyterminal parathyroid hormone (PTH) concentration (homologous measurement of the 53-84 fragment and heterologous bovine measurement) has been measured and correlated with both clinical and radiological findings of secondary hyperparathyroidism (HPT), studied quantitatively according to a score published in literature, in 95 patients with chronic renal failure on maintenance hemodialysis. Mean serum PTH concentration (53.84) is statistically higher in patients with severe clinical and radiological evaluation of HPT than in patients with moderate or slight manifestations of HPT (M +/- DS: 515.8 +/- 243.7 pg/ml VS 271.3 +/- 166.1 pg/ml p less than 0.001). However, even with high serum concentration, serum PTH level does not allow to predict HPT severity, suggesting a retention of PTH fragments in serum without biologic activity probably.

[Feedback of the magnesium ion on the parathyroid hormone: differences in the action of magnesium sulfate and pyrrolidone carboxylate]. / Rétrocontrôle de l'ion magnésium sur la parathormone: différences d'action du sulfate et du pyrrolidone carboxylate de magnésium.

Fourty-five minutes after an intravenous injection of Mg SO4 (170 mg of element Mg), in 7 young and healthy men, a significant decrease in circulating 53-84 PTH has been observed. An injection of magnesium pyrrolidone carboxylate (170 mg of Mg) failed to induce changes in plasma levels of PTH. The urinary excretion of Mg was 2-fold higher after the injection of Mg SO4 than after the injection of magnesium pyrrolidone carboxylate. For both magnesium salts used, the time patterns of plasma magnesium concentrations were the same and red blood cells magnesium was not increased. These results suggest that, in our experimental conditions, the retention of magnesium was higher after magnesium pyrrolidone carboxylate than after Mg SO4 and that the drop in plasma PTH could partly explain the larger urinary excretion of magnesium after Mg SO4.

Effect of the variations of female sex hormones during the menstrual cycle upon serum somatomedin and growth-promoting activity.

Serum growth-promoting activity measured upon lymphocytes, sulfation activity and radioimmunoassayable somatomedin C (Sm-C) levels were measured in sera from women during the menstrual cycle. The data showed that: estradiol, progesterone, LH or FSH added in vitro do not increase the 3H-thymidine uptake into lymphocytes; the serum thymidine activity decreases during the luteal stage of the cycle, and is negatively correlated with the progesterone levels; the sulfation factor and Sm-C levels do not have significant variations during the menstrual cycle, and the GH maximum values are attained during the luteal stage.

PIP: This study investigated variations in thymidine activity, sulfation activity, and radioimmunoassayable somatomedin C levels during the menstrual cycle and the direct effect of female sex hormones on 3H-thymidine incorporation into lymphocytes in vitro. Subjects included 8 healthy women 24-46 years of age from whom a total of 49 venous blood samples were obtained. Estradiol, progesterone, luteinizing hormone, or follicle stimulating hormone added in vitro did not increase 3H-thymidine uptake into lymphocytes. The serum thymidine activity level was observed to decrease during the luteal phase of the menstrual cycle and was negatively correlated with the progesterone levels. The sulfation factor and somatomedin C levels did not have significant variations during the menstrual cycle. Finally, growth hormone maximum values were attained during the luteal phase. The negative correlation of thymidine activity levels with progesterone values suggests that more than one thymidine activity measures all serum factors.

[Effects of human growth hormone on very short children with intermediate responses to somatotropic stimulation tests]. / Effets de l'hormone de croissance humaine sur les enfants de très petite taille avec réponses intermédiaires aux épreuves de stimulation somatotrope.

The effects of treatment with human growth hormone (hGH) were studied in 29 patients aged 2 to 16 years with growth retardation between 2.2 and 6 standard deviations and insufficient growth velocity in whom repeated pharmacologic somatotropic stimulation tests had shown discordant responses either above 7 ng/ml, or lower than 6 ng/ml. An important acceleration of growth was obtained in 10 of 16 patients before puberty and in all the 13 cases treated at the beginning of puberty. No correlation was observed between the GH levels observed during the stimulation tests and the clinical results of treatment. These data lead to discuss partial GH deficiency and to propose a trial of treatment in very short children with low and/or dissociated responses to repeated tests of pituitary somatotropic secretion.

Comparison of growth hormone sleep release and responses to pharmacological tests.

The spontaneous release of growth hormone (GH) during nocturnal sleep was studied at age 5-19 years in 44 male and 15 female patients with severe growth retardation (-2.1 to -6.5 SD) among whom 43 were prepubertal and 16 pubertal. Comparison with the results of classical stimulation tests with ornithine, arginine and/or insulin showed good agreement in cases of classical hypopituitarism (n = 14) as in patients who seemed to be endocrinologically normal (n = 27). In 18 patients (31%) there was a discrepancy between sleep release and responses of GH to stimulation test: treatment with hGH was available in only 4 of these children and enhanced sharply their growth rate. It is suggested that a large span of intermediary situations exists between normal GH secretion and complete GH deficiency, deserving a controlled therapeutic trial with hGH.

Prolactin and thyrotrophin responses to thyroliberin (TRH) in patients with growth hormone deficiency: study in 167 patients.

Both thyrotrophin (TSH) and prolactin (Prl) were studied under thyroliberin (TRH) stimulation tests in 167 hypopituitary dwarfs out of GH or T4 treatment. TSH and/or Prl responses were either low, normal or exaggerated and/or protracted. Various abnormal patterns were observed in most of the patients with low T4 but also in many patients with normal T4. The TSH response should be considered together with the value of T4. A normal response of TSH with a low T4 reflects a relative TSH deficiency from pituitary or hypothalamic origin. There was no clear relationship between the cause or type of hypopituitarism and the pattern of the responses of either TSH or Prl. The abnormalities of TSH and Prl were not related to each other except in patients with a past history of breech delivery. Then both TSH and Prl have to be measured after TRH in order to obtain full information from the test about hypothalamo-pituitary function. The frequency of the exaggerated and/or delayed or protracted responses of TSH and Prl with normal or low T4 is probably mostly related to hypothalamo-pituitary dysfunction. Abnormal responses of TSH or Prl, seldom of both hormones, were observed in otherwise isolated growth hormone (GH) deficiency, leading to a modification of such a diagnosis after the TRH test. Actually, the TRH test may be useful to ascertain the diagnosis of GH deficiency when the GH responses to provocative tests are borderline.

[Relationships between growth, and plasma growth hormone and growth factors under normal physiological conditions and during pathological states (author's transl)]. / Relations entre croissance, hormone de croissance et facteurs de croissance plasmatiques en physiologie et en pathologie.

Growth hormone (GH) and somatomedin (Sm) are the main factors of human growth. Sm is GH-dependent, but Sm increase after hGH injection in hypopituitary dwarfs is slow, and preceded by a decrease. The liver and kidneys are the main places of Sm production in vivo, the liver having probably also a regulatory effect. In vitro, GH-dependent production of Sm may be obtained from fibroblasts as well as from liver cells. Sm activates thymidine uptake by cultured human fibroblasts and by activated human lymphocytes, this effect needing cofactors from serum. Discrepant correlations between growth, GH and Sm are found in some pathological situations, such as obesity, craniopharyngioma, celiac disease, infantile malnutrition. Moreover, transferrin, a plasma protein, correlates also with growth.

[Early effects of intramuscular growth hormone on plasma somatomedin activity (author's transl)]. / Effets à court terme de l'injection d'hormone de croissance sur l'activité somatomédine du plasma.

The early effects of intramuscular injection of human growth hormone (hGH) on plasma sulfation activity (Sm) have been followed for 72 hours: 1) after one injection of 6 mg in control children and in pituitary dwarfs (isolated idiopathic GH deficiency, multiple idiopathic pituitary deficiencies, and post-surgical or post-radiotherapic hypopituitarism); 2) after 6 injections of 1 mg every 12 hours in idiopathic pituitary dwarfs. Following injection of 6 mg, Sm decreases during 2-4 hours in all groups studied, then rises and peaks at 24 hours. The early decrease of Sm could relate to a rise of Sm-binding protein, as suggested by data obtained in the dog after intravenous injection of bovine GH. Following 6 injections of 1 mg, the rise of Sm is slower but higher and more protracted than with one injection of 6 mg. This fact suggests that the clinical effects of fractionation of treatment with HGH require further study. The lack of correlation between the biological data obtained and the clinical effects of hGH treatment upon the growth of pituitary dwarfs shows that the short-term hGH test used does not allow to foresee the effects of treatment.

Correlative study of radioreceptor assay and radioimmunoassay of serum growth hormone in children. II: Primary, genetic and intra-uterine growth retardation.

Growth hormone (GH) was measured by radioreceptorassay (RRA) and radioimmunoassay (RIA) in the sera of 24 children with idiopathic primary growth retardation (PGR), 15 with genetic short stature (GSS) and 11 with intra-uterine growth retardation (IUGR), and compared to results obtained in normal children. The average RRA/RIA ratio was close to normal in PGR (1.02 +/- 0.05) and in IUGR (1.06 +/- 0.07), and slightly though not significantly lower in GSS (0.86 +/- 0.06). Some variability in RRA/RIA ratio was found in individual patients of each group, and some sera gave a non-parallel displacement of the tracer when compared to the standard curve. But no genetic difference of RRA-assayable GH was found between the three groups studied and normal children.

Correlative study of radioreceptor assay and radioimmunoassay of serum growth hormone in children: normal children and HGH-treated pituitary dwarfs.

A sensitive and reproducible radioreceptor assay (RRA) for human growth hormone (HGH) is described. It allows the evaluation of HGH concentrations as low as 2 ng/ml. It has a limited cross-reactivity with human prolactin, which does not interfere at physiological levels in children. Comparison of the results with those of radioimmunoassay (RIA) showed no discrepancies in the serum of normal children before and after stimulation tests for GH (mean RRA/RIA ratio 1.03 +/- SEM 0.04, range 0.75 to 1.65) nor in the serum from hypopituitary dwarfs during the 12 h following an im injection of 6 mg of HGH (mean RRA/RIA ratio 1.05 +/- 0.04, range 0.84 to 1.28). It is concluded that receptoractivity of HGH is parallel to its immunoreactivity in normal children and in hypopituitary patients clinical grade HGH.

[Prolactin secretion and synthesis by human somatotropin adenomas: in vitro effect of somatostatin (SRIF) (author's transl)]. / Secrétion et synthèse de la prolactine par les adénomes somatotropes humains en culture organotypique. Effet de la somatostatine (SRIF).

Human somatotropin secreting adenomas removed from acromegalic patients were submitted to organ culture for periods of up 1 to 4 hours and 1 to 2 weeks. Prolactin (PRL) secretion increased in most of the experiments during the different culture times while growth hormone (GH) secretion decreased slowly in some of them. After incorporation of 3H leucine, 3H GH and 3H PRL were obtained in short and long term organ culture giving evidence for "de novo" synthesis. SRIF inhibited PRL as well as GH secretion after 1 to 4 hours incubation.