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Biomedical subjects

B Conte-Devolx

Publications and source records attributed to B Conte-Devolx.

At least 19 recordsLinked to original sources

[Malignant endocrine tumor of the pancreas associated with high blood thyrocalcitonin levels].

A case of thyrocalcitonin-secreting endocrine tumour of the pancreas is reported. Endocrine pancreatic tumours are neoplasias evolving over a long period; most of them are multisecreting, usually with a predominant secretion responsible for clinical symptoms. In this particular case the retrospective diagnosis of a thyrocalcitonin-secreting tumour of the pancreas was made by immunocytochemical study of the pancreatectomy specimen. One year after pancreatectomy, the persistence of clinical signs and a plasma thyrocalcitonin level higher than 25,000 pg/ml led to the discovery of a liver metastasis. An immunocytochemical study of the segmental hepatectomy specimen showed a single population of thyrocalcitonin-secreting cells identical with those found in the pancreatic tumour. In this context, radioimmunological assays of peptides and immunocytochemistry seem to be the best diagnostic methods.

Aged

Age-related changes in cortico-releasing factor, somatostatin, neuropeptide Y, methionine enkephalin and beta-endorphin in specific rat brain areas.

We investigated the age-related changes in the tissular protein, cortico-releasing factor (CRF), somatostatin (SOM), neuropeptide Y(NPY), methionine enkephalin (M-ENK) and beta-endorphin (beta-END) levels in frontal cortex, hippocampus, striatum and hypothalamus of young (4-month-old), mature (18-month-old) and senescent (26-month-old) Wistar male rats, bred in a specific pathogen free environment. Between the age of 4 and 18 months, the tissular protein levels increased in all 4 structures studied. The CRF and SOM levels increased in the hippocampus, while the NPY levels decreased. During this time, the NPY content increased in the striatum, whereas the SOM and M-Enk striatal levels decreased. Concomitantly, the NPY and beta-End levels decreased in the hypothalamus. Interestingly, no significant variations were found to occur in the frontal cortex whatever the neuropeptide studied. Between the age of 18 and 26 months, no significant changes in the tissular protein levels were detected, except in the hippocampus. The changes in the neuropeptide concentrations observed during this period depended on the neuropeptide and the brain structure studied. The CRF and beta-End levels decreased in the frontal cortex and the hypothalamus, respectively. The NPY peptidergic systems seem to be preferentially affected by aging processes since 3 out of the 4 structures studied--the frontal cortex, the striatum and the hypothalamus--showed a decrease in their tissular NPY content. During the same period, none of the 5 neuropeptides studied were affected in the hippocampus.

Aging

Acute changes in growth hormone-releasing hormone secretion after injection of BIM 23014, a long acting somatostatin analog, in rams.

BIM 23014 is a somatostatin analog displaying an increased biological half life due to resistance to enzymatic degradation. This peptide inhibits GH release directly at the level of pituitary somatotrophs. In addition, an action of BIM 23014 at the level of the hypothalamus is possible since somatostatinergic fibers and receptors have been identified on GH-RH neurons. To evaluate the effect of BIM 23014 on GH-RH secretion, hypophysial portal blood (HPB) was continuously collected in conscious sheep. Twelve rams (40-45 kg, 9-month-old) with chronically implanted perihypophysial cannulae were i.v. injected with BIM 23014 (1 mg) or saline. HPB and jugular blood were collected for 3-5 hours before and after the injection for the determinations of GH-RH and GH concentrations respectively. The acute injection of BIM 23014 induced a rapid decrease of plasma GH within the first two hours. Simultaneously, GH-RH in HPB decreased significantly. After reaching a nadir, GH concentrations increased to values greater than baseline. A similar rebound in GH-RH levels in HPB was also observed. These data indicate that BIM 23014 acts at the level of GH-RH hypothalamic neurons, in addition to its well-know effect on the pituitary gland.

Animals

Effect of chronic active immunization anti-corticotropin-releasing factor on the pituitary-adrenal function in the sheep.

ACTH and cortisol diurnal variations and responses to two types of stress (insulin-induced hypoglycemia and isolation-restraint stress) or to an acute injection of lysine-vasopressin were studied in intact and anti-corticotropin-releasing factor (CRF) actively immunized rams. Immunization was obtained by the injection of synthetic ovine CRF coupled to BSA with carbodiimide. All animals developed antibodies anti-CRF and displayed an alteration of their general condition and a body weight reduction. The mean basal ACTH and cortisol secretion as well as the number and mean amplitude of diurnal pulses of these hormones was significantly reduced in the group of anti-CRF immunized rams. However, the reduction in all three parameters was much more pronounced for cortisol than for ACTH. No ACTH and cortisol response to insulin-induced hypoglycemia and isolation-restraint stress was observed. The stimulating action of lysine-vasopressin on ACTH release was significantly reduced as compared to controls. These results indicate that CRF is a major physiological component of the ovine hypothalamo-hypophysial-adrenal axis and participates in the events that regulate ACTH and cortisol diurnal variations and response to stress.

Adrenocorticotropic Hormone

Effect of chronic active immunization with antiarginine vasopressin on pituitary-adrenal function in sheep.

ACTH and cortisol diurnal variations and responses to two types of stress (insulin-induced hypoglycemia and isolation-restraint stress) and to an acute injection of CRF were determined in intact as well as in actively antiarginine vasopressin (AVP)-immunized rams. All immunized sheep developed antibodies to AVP, displayed diabetes insipidus, and looked healthy in spite of their lower gain weight. Basal secretion and diurnal variations of ACTH and cortisol were unaltered in the group of anti-AVP-immunized animals. In contrast, ACTH and cortisol responses to both types of stress and CRF injection were significantly reduced compared to those in controls. These results suggest that endogenous AVP plays a physiological role in the corticotropic response to stress. However, endogenous AVP does not appear to affect basal secretion and diurnal variations of ACTH and cortisol.

Adrenocorticotropic Hormone

Effects of metyrapone infusion on corticotropin-releasing factor and arginine vasopressin secretion into the hypophysial portal blood of conscious, unrestrained rams.

The effects of rapid changes of circulating cortisol levels on ACTH secretion and on corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) concentrations into hypophysial portal blood were studied in six adult rams. Pharmacological adrenalectomy was obtained by 3 h metyrapone infusion (100 mg.kg-1.h-1). Blockade of cortisol synthesis induced a tenfold increase of plasma ACTH levels accompanied by a moderate increase of CRF secretion (150% vs preinjection levels) and a large increment of AVP secretion (535% vs preinjection levels). ACTH levels remained high during the 3 h following the end of metyrapone infusion. During the same period, CRF secretion was still elevated (231% vs preinjection levels), while AVP secretion was further stimulated (2,151% vs preinjection levels). Subsequent hydrocortisone infusion (66 micrograms.kg-1.h-1) for 2 h induced a rapid decrease of both ACTH and AVP secretion, while CRF levels in hypophysial portal blood still remained elevated. These data suggest that changes in ACTH secretion induced by acute modifications of the negative glucocorticoid feedback are, in addition to the well documented direct effect of cortisol on the corticotropes, mainly mediated by variations of hypothalamic AVP secretion.

Animals

[Serum human growth hormone assay. Comparison of six assay kits].

Measurements of human growth hormone (hGH) plasma levels using mono or polyclonal antibodies based on kits are often highly variable depending upon the kit used. We compared six kits commercially available: one based on polyclonal antiserum, five based on monoclonal antisera. We measured 695 sera obtained in short stature children (GH deficiency or normal GH secretory) and adults (normal, hypopituitarism or acromegaly). Our results confirm the variability between the assays. The maximal variation was obtained with SBhGH kit which showed mean results 1.7 fold higher than those obtained with hGH Coatria. Using the OMS 80.205 standard with the six kits, we found a good correlation between the six kits indicating that the standard used in each case was not responsible for the observed variations. This suggest that the different antibodies used in these kits may recognize different isoforms of circulating hGH. In addition variations in reagents used in the different kits may also explain these discrepancies. The variations observed using these six commercially available kits may have important clinical repercussion and especially may impede the diagnosis in hGH deficiency in children.

Adolescent

[Bone density after iatrogenic subclinical long-term thyrotoxicosis. Measurement by dual photon absorptiometry].

Thyrotoxicosis may be held responsible for osteoporosis. The question is whether a very slight subclinical hyperthyroidism, as is desirable in the post-operative treatment of differentiated thyroid carcinoma, can in the long run be detrimental to bone tissue. In a series of 37 patients, aged 50.9 +/- 11.1 years, presenting with the features of subclinical hyperthyroidism of 8.0 +/- 4.8 years duration, the authors have been unable to find any change in paraclinical parameters of bone and calcium-phosphate metabolism. Thirty-six of these 37 patients showed no abnormal decrease of vertebral bone density measured by dual photon absorptiometry.

Absorptiometry, Photon

Insulin-induced hypoglycemia stimulates corticotropin-releasing factor and arginine vasopressin secretion into hypophysial portal blood of conscious, unrestrained rams.

Insulin-induced hypoglycemia (IIH) is a strong stimulator of pituitary ACTH secretion. The mechanisms by which IIH activates the corticotrophs are still controversial. Indeed, in rats the variations of corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) secretion in hypophysial portal blood (HPB) during IIH have been diversely appreciated. This may be due to the stressful conditions required for portal blood collection in rats. We studied the effects of IIH on the secretion of CRF and AVP in HPB and on the release of ACTH and cortisol in peripheral plasma in conscious, unrestrained, castrated rams. After the injection of a low (0.2 IU/kg) or high dose (2 IU/kg) of insulin, ACTH and cortisol levels in peripheral plasma increased in a dose-related manner. After injection of the low dose of insulin, CRF and AVP secretion in HPB were equally stimulated. After injection of the high dose of insulin, CRF secretion was further stimulated, while AVP release was dramatically increased. These results suggest that when the hypoglycemia is moderate, CRF is the main factor triggering ACTH release, and that the increased AVP secretion potentiates the stimulatory effect of CRF. When hypoglycemia is deeper, AVP secretion becomes predominant and may by itself stimulate ACTH release.

Adrenocorticotropic Hormone

Glucocorticoids regulate peptidyl-glycine alpha-amidating monooxygenase gene expression in the rat hypothalamic paraventricular nucleus.

Peptidyl-glycine alpha-amidating monooxygenase (PAM) is a posttranslational processing enzyme which catalyzes the formation of biologically active alpha-amidated peptides. The two major neuropeptides involved in the regulation of ACTH secretion [CRF and arginine vasopressin (AVP)], synthesized in the parvocellular part of the hypothalamic paraventricular nucleus (PVN), are amidated, and their synthesis and/or release is negatively regulated by glucocorticoids. In this study, using in situ hybridization, we have shown that PAM mRNA is abundantly expressed in the hypothalamic paraventricular and supraoptic nucleus. Surgical adrenalectomy (ADX) induced increases in PAM, CRF, and AVP mRNA in the parvocellular part of the PVN, while corticosterone treatment normalized these values. PAM and AVP gene expression were not changed in the magnocellular part of the PVN or in the supraoptic nucleus. These observations suggest that in addition to stimulation of CRF and AVP synthesis, ADX induces an increase in PAM synthesis in the PVN and, thus, support the hypothesis of increased secretion of both CRF and AVP after ADX.

Adrenalectomy

Corticotropin-releasing factor secretion increases in rat hypophysial portal blood during insulin-induced hypoglycemia.

To study the possible involvement of hypothalamic corticotropin-releasing factor (CRF) in the stimulation of adrenocorticotropic hormone (ACTH) release caused by insulin-induced hypoglycemia (IIH), we measured CRF secretion in hypophysial portal blood (HPB) in rats anesthetized with sodium thiopental after injection of insulin. Before treatment, systemic ACTH levels (952 +/- SE 143 pg/ml; n = 12) were well above normal values, probably reflecting the anesthetic and surgical stress consecutive to the preparation for portal blood collection. Insulin injection induced a significant increase of ACTH release within 15 min (1,588 +/- 168 vs. 741 +/- 144 pg/ml; n = 6, in vehicle-injected rats) which lasted for at least 1 h. CRF levels in HPB were 857 +/- SE 168 pg/ml (n = 13) during the first-hour pretreatment collection. Vehicle injection did not modify CRF secretion (759 +/- 142 pg/ml; n = 6). Insulin injection provoked a significant increase in CRF release (1,449 +/- 257 pg/ml; n = 7). These data suggest that an increased hypothalamic CRF secretion is responsible for the stimulation of pituitary ACTH release following IIH. The possible involvement of central neuromediators in the IIH-induced CRF production is discussed.

Adrenocorticotropic Hormone

In vitro corticotropin-releasing hormone (CRH) stimulation of adrenocorticotropin release from corticotroph adenoma cells: effect of prolonged exposure to CRH and its interaction with cortisol.

To examine if down-regulation of CRH-induced ACTH release occurs in corticotroph adenoma cells as well as CRH-glucocorticoid interactions in these cells, we established primary cultures of pituitary adenoma cells obtained by transphenoidal surgery from five patients with Cushing's disease. To prevent binding of glucocorticoids by serum proteins, we used a serum-free medium containing insulin, transferrin, selenium, and epidermal growth factor. The latter was found to be essential for both basal and CRH-stimulated ACTH secretion. CRH acutely stimulated, in a dose-dependent manner, ACTH release by all adenomas studied, with an IC50 of 0.5 X 10(-9) mol/L. Prolonged exposure (10 days) to a half-maximal stimulatory concentration of CRH led to continuous stimulation of ACTH secretion. A 4-day incubation with cortisol induced a dose-dependent decrease in both basal and long term CRH-stimulated ACTH release, with no difference in the IC50 (1 X 10(-8) mol/L). These data suggest that long term exposure to CRH does not desensitize corticotroph adenoma cells. Thus, it is unlikely that long-acting analogs of CRH will be useful in the treatment of Cushing's disease. ACTH secretion from corticotroph adenomas is restrained by glucocorticoids; the sensitivity of these cells to the negative effect of glucocorticoids is not modified by long term stimulation with CRH.

Adenoma

The corticotropin-releasing factor release in rat hypophysial portal blood is mediated by brain catecholamines.

In order to study the involvement of the hypothalamic corticotropin-releasing factor (CRF) in catecholamine-induced adrenocorticotropin (ACTH) secretion, we have measured CRF levels in rat hypophysial portal blood (HPB) after the pharmacological destruction of the ventral noradrenergic bundle (VNAB), using 6-hydroxydopamine (6-OHDA) stereotaxically injected into the VNAB. CRF levels in HPB were measured by radioimmunoassay, and the effects of 6-OHDA injection were controlled by the determination of catecholamine concentrations in the total hypothalamus. VNAB lesions induced a dramatic decrease in norepinephrine and epinephrine hypothalamic concentration. The CRF levels in HPB were also significantly reduced. These results suggest that central catecholamines exert a direct stimulatory control on the CRF release and play a major role in stress-induced ACTH secretion.

Adrenocorticotropic Hormone

Effects of chronic maternal dexamethasone treatment on the hormones of the hypothalamo-pituitary-adrenal axis in the rat fetus.

Different hormones of the hypothalamo-pituitary-adrenal axis (corticotropin-releasing factor, adrenocorticotropic hormone, corticosterone) were measured in brain pieces (stalk, median eminence, hypothalamus), hypophyses, adrenals and plasma of 21-day-old rat fetuses from mothers which were given either plain tap water or water containing dexamethasone acetate (10 micrograms/ml) from day 15 to 21 of gestation. Dexamethasone induced drastic reduction of body weight (-66% vs. controls), severe atrophy of the adrenals (-83%) and a sharp drop in their corticosterone content (-74%). Fetal plasma corticosterone levels were below the lower limit of detection of the competitive corticosteroid-binding globulin (CBG) radioassay (less than 0.01 microgram/ml). Both atrophy and severe reduction of the adrenal activity in fetuses from dexamethasone-treated females were in good correlation with a drastic decrease in plasma adrenocorticotropic hormone (ACTH) levels which were below the lower limit of detection of the radioimmunoassay (RIA) used (less than 10 pg/ml) and a significant reduction in pituitary ACTH content (-93%). The low corticostimulating activity of the fetal hypophyses was associated with a drop in both corticotropin-releasing factor (CRF) hypothalamic content (-57%) and concentration (-67%). The effects of dexamethasone on plasma and pituitary ACTH concentrations in 21-day-old fetuses were compared to those, previously reported, of encephalectomy and decapitation performed on day 16 of gestation. The reported data were consistent with the present results, suggesting both pituitary and hypothalamic sites for the in vivo inhibiting action of dexamethasone on the rat hypothalamic-pituitary-adrenal axis in late gestation.

Adrenocorticotropic Hormone

Corticoliberin, somatocrinin and amine contents in normal and parkinsonian human hypothalamus.

We have compared hypothalamic contents of various neurotransmitters (dopamine (DA), norepinephrine and serotonin) and their metabolites (dihydroxyphenyl acetic acid, homovanilic acid, 5-hydroxyindoleacetic acid) in post-mortem human controls and parkinsonian hypothalami. Neurotransmitters and their metabolites were measured in 0.1 N HCl hypothalami extracts using electrochemical detection after high performance liquid chromatography. Using specific radioimmunoassays we have also measured corticoliberin and somatocrinin contents in these hypothalami. Despite a 50% decrease of DA contents in parkinsonian hypothalami, no variations of corticoliberin and somatocrinin contents were found: 16.6 +/- 1.78 pg/mg tissue in Parkinson disease vs 16.71 +/- 1.89 in controls for human corticotropin-releasing factor (hCRF 1-41) and 37.38 +/- 11 vs 45.16 for human growth-hormone-releasing factor (hGRF 1-44).

3,4-Dihydroxyphenylacetic Acid