[Immunohistochemical detection of calcitonin, ACTH, beta-MSH, beta-endorphin and somatostatin in medullary carcinoma of the thyroid. Immunoperoxidase study (PAP, ABC) of 10 cases]. / Détection immunocytochimique de calcitonine, d'ACTH, de beta MSH, de beta-endorphine et de somatostatine dans les carcinomes médullaires de la thyroïde. Etude en immunoperoxydase (PAP, ABC) de 10 cas.

Ten cases of Medullary carcinoma of Thyroid gland (MCT) were examined (two familial, eight sporadic) in patients with increased serum calcitonin levels and ranging age from 31 to 87 years. Immunocytochemical reactions were performed using Peroxidase-Antiperoxidase (PAP) complex and/or Avidin-Biotin-Peroxidase complex (ABC) by light microscopy on fixed tumorous specimens (10 cases) and additionally by electron microscopy (3 cases). The tumors displayed light microscopic features typical of MCT. The cells were polyhedral, angular or fusiform and showed high affinity for Grimelius stain. Large deposits of amyloid were Congo red stained and disclosed a green birefringence in polarized light. In the familial cases sections of non-tumorous thyroid tissue showed C cell hyperplasia. Electron microscopic studies revealed intracytoplasmic secretory granules and amyloid fibrils. The immunoperoxidase technique demonstrated calcitonin in the tumor cells in all the cases, with a weaker staining than in para-and intra-follicular C cells of adjacent non tumorous tissue and than in C cells hyperplasia foci, when present. Immunoreactive tumor cells were also observed with anti SRIF in 4 cases, with anti-ACTH and anti-beta MSH in 3 cases, and with anti-beta endorphin in 2 cases. These results are discussed with a review of the literature.

Adrenocorticotropin, and corticosterone secretion in Brattleboro rats.

Brattleboro rats which lack endogenous vasopressin have been used to study the role of vasopressin as a corticotropin-releasing factor. Plasma ACTH, beta-endorphin, and corticosterone were measured by RIA in male and female Long-Evans and Brattleboro rats under the following conditions: unstressed, after ether stress, after nicotine injection, and after adrenalectomy. A significant reduction in the ACTH, beta-endorphin, and corticosterone responses to the different experimental procedures was observed in the Brattleboro rats. However, in this strain of rats, a significant increase in the release of all three hormones was obtained, suggesting that vasopressin has only a synergistic role in the regulation of their secretion.

[Determination of plasma catecholamine. Effects of glucagon administration]. / Dosage des catécholamines plasmatiques. Effets de l'administration de glucagon.

Basal plasma dopamine (DA), Norépinephrine (NE) and Epinephrine (E) were determined in controls (n = 15) essential hypertension (n = 19) and Pheochromocytoma (n = 9). Plasma NE was significantly higher in essential hypertension than in control and in 5 cases, plasma NE or E was 3 SD above mean control values. In 8/9 pheochromocytomas DA, E or NE were significantly elevated. In 1 case, catecholamine levels were within normal range during normotensive period. When a provocative glucagon test (1 mg I.V) was performed in controls, there was no change in blood pressure DA and NE levels, but a significant increase in plasma E 2.5 and 5 min. after injection. Similar results were obtained in 8/10 cases of labile hypertension. However in 2 cases plasma NE or E increased significantly without elevation in blood pressure. In 3/4 pheochromocytomas under normotensive phase, blood pressure and plasma catecholamines increased significantly; however in 1 case, no change was observed.

Influence of endogenous somatostatin on growth hormone and thyrotropin secretion in neonatal rats.

When gestating rats were injected iv with an antiserum to somatostatin (SRIF-AS) during the last week of gestation, serum GH levels in fetuses and 6-h-old newborn rats were not significantly different from controls. Similarly, 2 h after the ip administration of SRIF-AS, no change in serum GH concentration was observed in 2-h-old rats. However, under the same conditions, a significant increase in serum GH was observed in 24-h-old rats and in 2- to 60-day-old rats. The injection of SRIF-AS neither changed basal serum TSH levels during the neonatal development nor in the adult stage. A significant increase in TRH-induced TSH release was observed after the third postnatal day. It is concluded that endogenous SRIF plays a physiological role in GH release by 24 h of age in the rat and that the fall in GH secretion that normally occurs during the first week of life is due to the development of inhibitory mechanisms mediated by hypothalamus SRIF. Additionally the results suggest that the influence of SRIF upon TSH secretion is present before that of TRH.

Influence of thyrotropin-releasing hormone on the secretion of thyrotropin in neonatal rats.

Two hours after the ip administration of TRH antiserum, no change in serum TSH concentration was observed in the rat from birth through day 5 of life. Under the same conditions, a significant reduction in serum TSH was observed in 7- to 14-day-old rats. Similarly, in neonatal hypothyroidism, TSH levels did not change in 1-day-old rats, whereas a significant decrease was observed on day 7. The administration of synthetic TRH during the neonatal period induced a significant increase of serum TSH in the newborn; however, TSH release by the pituitary gland increased progressively from days 3-10. Immunoreactive TRH was undetectable in the serum of newborn rats. Adult levels were reached when the rats were 10 days old. It is concluded that neonatal pituitary-thyroid function in the rat is not physiologically dependent upon TRH secretion, although synthetic TRH is able to stimulate the secretion of TSH at birth.

Effect of neonatal treatment with monosodium glutamate on the secretion of alpha-MSH, beta-endorphin and ACTH in the rat.

Plasma alpha-MSH, beta-endorphin and ACTH were measured at 60 days of age in rats which had been injected during the neonatal period with monosodium glutamate (MSG). Although the arcuate nucleus tuberoinfundibular dopaminergic and cholinergic system was lesioned by the MSG, no change in circulating alpha-MSH, ACTH and corticosterone levels was observed under basal conditions, after ether stress of adrenalectomy. In contrast, a moderate, but significant decrease in plasma beta-endorphin was noticed after MSG treatment.

beta-Endorphin is present in high concentration in the hypophysial portal vessels of rats.

beta-Endorphin-like immunoreactivity (beta-ELI) was measured in hypophysial portal and arterial blood of intact, adrenalectomized and hypophysectomized rats. beta-ELI levels were 61 times higher in the long portal vessels than in the general circulation. Circulating, and especially portal, levels of beta-ELI were significantly increased after adrenalectomy. After removal of the pituitary gland, the mean level of beta-ELI in portal blood was significantly lower than in intact rats. beta-ELI in portal blood displayed the same chromatographic properties as synthetic beta-endorphin.

[Discordance of total plasma l-triiodothyronine and l-thyroxine in thyroid diseases]. / Discordance des taux plasmatiques de l-triiodothyronine et de l-thyroxine totales dans les maladies thyroïdiennes.

Radioimmunoassay (RIA) for plasma T3 has been proposed in the diagnosis of thyroid disease. 1 171 simultaneous determination (RIA) of plasma Thyrotropin-Stimulating Hormone (TSH), triiodothyronine (T3) and thyroxine (T4) have been performed in unselected patients under suspicion of a thyroid disease. 81.8% of the cases showed a good agreement between T3 and T4 levels. The remaining 18.2% can be divided into 6 groups: 1. High T3-normal T4 : 51% of the discrepancies: Graves disease untreated (16%) or treated (4%); sporadic goiter (13%); growth failure (8%); hypothyroidism under treatment (6%); thyroiditis, Graves ophtalmopathy, toxic adenoma (4%); 2. High T3-low T4 : 6.5%; sporadic goiter (3%); hypothyroidism (3%); 3. Normal T3-low T4 : 22%: Graves disease under treatment (6%); sporadic goiter (4.5%); subacute thyroiditis (3%); hypothyroidism (3%); miscellaneous (5.5%); 4. Normal T3-High T4 : 9.5%; thyroidectomized patients for cancer well-substituted with T4 (6%); miscellaneous (3.5%) including 1 case of Graves disease; 5. Low T3-normal T4 : 8% 8%: sporadic goiter (4%); hypothyroidism (2%); treated hyperthyroidism (2%); 6. Low T3-high T4 : 3% : including 1 case of hyperthyroidism and 2 cases of thyroidectomized patients well-substituted with T4. In conclusion discrepancies between T3 and T4 levels have been observed mainly in untreated or treated Graves disease (high T3-normal or low T4) and in hypothyroidism (normal or high T3-low T4). The basal TSH and TSH peak after I.V. injection of TRH (65 cases) are in better agreement with T4 level than with T3 level. Indeed, both TRS values are high when T4 is low while T3 is normal of high.

Influence of haloperidol on ACTH and beta-endorphin secretion in the rat.

The injection of haloperidol, a dopamine receptor blocker, was followed by a large increase of plasma ACTH and beta-endorphin-like immunoreactivity (beta-EI) in the rat. This effect was prevented when the rats were previously treated with corticosteroids. These results suggest that catecholamines inhibit ACTH and beta-endorphin secretion in the rat.

Brain TRH levels during development of the rat, in neonatal hypothyroidism and after caloric deprivation.

The effect of neonatal hypothyroidism and neonatal caloric deprivation on brain TRH levels and serum and pituitary TSH levels has been determined in rats on the following postnatal days: 1, 5, 10, 15, 25, 40 and 60. After neonatal hypothyroidism, there was a slight reduction in brain TRH content although TRH concentration in the brain increased. Serum TSH was elevated at birth, suggesting that the feedback of thyroid hormones on the pituitary gland acts in rat fetuses. After neonatal caloric deprivation, a decrease in brain TRH content was observed along with a decrease in circulating TSH levels, however, there was no change in brain TRH concentration.

[Hypothalamic control of ACTH secretion]. / Contrôle hypothalamique de la sécrétion d'ACTH.

The hypothalamic regulation of ACTH secretion has been reviewed. Recent biochemical investigations on corticotropin-releasing factor (CRF) suggest that CRF is present in the hypothalamus under two or more different molecular weight forms, their structure being not elucidated yet. Vasopressin has a CRF-like activity. However, contradictory results have been reported on the role of AVP as a physiological CRF. The synthesis of CRF appears to occur in a large hypothalamic area outside the median eminence. CRF-carrying fibers are thought to pass through the lateral retrochiasmatic area and project on the hypophysial portal vessels at the junction between the pituitary stalk and the median eminence. Conflicting data have been published on the influence of monoamines on ACTH secretion. In the dog, ACTH release is inhibited by the alpha-adrenergic receptors, this effect being not as clearly demonstrated in other species. The stimulation of nicotinic and muscarinic receptors followed by increased ACTH secretion. Glucocorticoids appear to lower ACTH secretion through an action at both the hypothalamic and pituitary levels.

[Immunoreactive somatostatin in rat hypophysial portal blood (author's transl)]. / Concentration de somatostatine dans le sang porte hypophysaire du rat.

Somatostatin levels have been determined by radioimmunoassay in hypophysial portal blood of pentobarbital-anesthetized male rats. In euthyroid rats, the mean level was 158 +/- 27 pg/ml (n = 8); somatostatin was undetectable (less than 30 pg/ml) in systemic blood of these rats. Thyroidectomy and excess of T4 did not modify the levels of somatostatin in hypophysial portal blood.

Immunoreactive somatostatin in rat hypophysial portal blood.

Somatostatin levels have been determined by RIA in hypophysial portal blood of pentobarbital-anesthetized male rats. In most animals, immunoreactive somatostatin (SRIF) levels were higher in hypophysial portal blood than in systemic blood. In euthyroid rats, the mean level was 158 +/- 27 pg/ml (n = 8); SRIF was undetectable (less than 30 pg/ml) in systemic blood of these rats. It is suggested that endogenous SRIF was not degraded during the collection of stalk blood, since synthetic SRIF is stable when incubated in rat serum during 4 min at 37 c and 2 h at 0 C, i.e. under the conditions the blood was kept during the collection. SRIF in hypophysial portal plasma had the same immunoreactivity with a specific antiserum against SRIF as did synthetic SRIF. Gel filtration of hypophysial portal plasma revealed two immunoreactive peaks, the major one corresponding to synthetic SRIF, the smaller one representing a larger molecular form. Thyroidectomy and excess of T4 did not modify the levels of SRIF in hypophysial portal blood, suggestinc SRIF is stable when incubated in rat serum during 4 min at 37 C and 2 h at 0 C, i.e. under the conditions the blood was kept during the collection. SRIF in hypophysial portal plasma had the same immunoreactivity with a specific antiserum against SRIF as did synthetic SRIF. Gel filtration of hypophysial portal plasma revealed two immunoreactive peaks, the major one corresponding to synthetic SRIF, the smaller one representing a large molecular form. Thyroidectomy and excess of T4 did not modify the levels of SRIF in hypophysial portal blood, suggesting that the feedback of thyroid hormones on TSH secretion does not involve changes in the secretion of SRIF by the hypothalamus.

[Systematic evaluation of 8 arginine vasopressin and neurophysins plasma levels in 10 patients with oat cells carcinoma of the lung (author's transl)]. / Dosage plasmatique systématique de l'hormone antidiurétique et des neurophysines dans dix cancers bronchiques primitifs à petites cellules.

Plasma AVP level, neurophysins and osmolality have been measured in 10 patients with oat cell carcinoma of the lung but without any biological signs of syndrome of inappropriate secretion of ADH (SIADH), before and 15 mn after an intravenous injection of Ethanol. No statistically significant difference was noted in the AVP, neurophysins and osmolality values between 10 patients with asymptomatic oat cell carcinoma and control population (10 normal volunteers, 12 patients with non neoplasic lung pathology and 10 patients with different lung carcinoma). We concluded that AVP and neurophysins cannot be considered as a good tumoral marker in the detection of oat cell carcinoma of the lung.

[Distribution of thyrotropin releasing hormone (TRH), alpha-melanocyte-stimulating hormone (alpha-MSH) and somatostatin in the skin of the green frog (Rana esculenta)]. / Distribution de thyrolibérine (TRH), alpha-melanocyte-stimulating hormone (alpha-MSH) et somatostatine dans les tissus de la Grenouille verte (Rana esculenta).

High concentrations of Thyrotrophin-Releasing Hormone (TRH) have been found in the dorsal skin of the Frog Rana esculenta, lower levels being measured in the ventral skin. alpha-MSH and somatostatin were undetectable in these tissues. Nor was TRH detected in the blood of these animals. The concentration of somatostatin in the pancreas was similar to that of the hypothalamus and twice or one hundred times higher than in the intestine or stomach respectively.