Search PubMed⌕ Search

Biomedical subjects

V Guillaume

Publications and source records attributed to V Guillaume.

At least 37 records · Page 2Linked to original sources
PubMed1994

Effect of streptozotocin-induced diabetes on somatostatin receptors in the anterior pituitary, hypothalamus and cerebral cortex of the male rat.

In order to better understand the mechanisms underlying the reduction in GH secretion in diabetic rats, we have characterized and measured SRIH receptors in the hypothalamus and anterior pituitary gland 5 and 9 days after induction of diabetes in the rat. Experimental diabetes was induced by an intraperitoneal injection of streptozotocin (STZ) at a dose of 65 mg/kg. Basal plasma GH was significantly reduced in diabetic rats. Chronic insulin replacement therapy partly restored plasma GH and blood glucose levels in these animals. A significant reduction in SRIH receptor concentrations was demonstrated in the hypothalamus and anterior pituitary gland, 5- and 9- days after STZ injection. These changes were not significantly corrected by insulin replacement. Cerebral cortex SRIH receptor concentrations were unaffected by experimental diabetes. We conclude that hypothalamic and pituitary SRIH receptor levels are lowered in diabetic rats. These changes may contribute to aberrant GH secretion in diabetes and they indicate that pituitary sensitivity to exogenous somatostatin should be tested in diabetic patients.

Animals↗
PubMed1994

Role of growth hormone (GH)-releasing hormone and somatostatin in the mediation of clonidine-induced GH release in sheep.

GH secretion is stimulated by the administration of an alpha 2-adrenergic agonist, clonidine, in several species, including man. This action is probably mediated at the level of the hypothalamus, where the drug may act through inhibition of somatostatin (SRIH) and/or stimulation of GH-releasing hormone (GHRH) release. We have investigated the mode and site of action of clonidine in sheep, because it is possible to collect hypophysial portal blood for the simultaneous determination of GHRH and SRIH in this species under conscious unstressed conditions. Clonidine injection (0.3 mg, iv) resulted in a significant, immediate, and short-lasting (30-min) increase in peripheral GH (14.4 +/- 3.1 vs. 4.8 +/- 1.1 ng/ml; P < 0.01) and portal GHRH (2.7 +/- 0.5 vs. 1.0 +/- 0.2 pg/min; P < 0.01) levels. No change in SRIH secretion was recorded during the same period. Next, we tested the effect of clonidine in sheep actively immunized against GHRH or SRIH. The alpha 2-adrenergic agonist did not affect GH secretion in the anti-GHRH group, whereas immunization against SRIH did not modify the GH response. Finally, we observed that clonidine did not influence GH release from cultured ovine pituitary cells. These data suggest that clonidine acts centrally to stimulate hypophysial GH secretion in the sheep and that this effect is mediated through changes in GHRH, but not SRIH, release into hypophysial portal blood.

Animals↗
PubMed1994

Growth hormone (GH)-releasing hormone secretion is stimulated by a new GH-releasing hexapeptide in sheep.

The acute effect of a new GH-releasing peptide, hexarelin (1 mg, iv), on GH secretion and the mechanisms involved in its changes were investigated in conscious sheep. Peripheral GH levels and GH-releasing hormone (GHRH) and somatostatin concentrations in hypophysial portal blood were measured in six rams. An increase in jugular GH levels was observed 15 min after hexarelin injection (9.1 +/- 1.8 vs. 3.9 +/- 0.8 ng/ml; P < 0.05). This was associated with a stimulation of GHRH release into hypophysial portal blood (145.4 +/- 19.9 vs. 59.2 +/- 10.8 pg/ml; P < 0.01) without a change in somatostatin secretion. Our data indicate that GH-releasing peptide-induced GH stimulation in the sheep involves an activation of GHRH neurons in addition to the previously demonstrated direct effect on the pituitary cells.

Animals↗
PubMed1994

Studies on the physiological role of ANF in ACTH regulation.

To investigate the impact of changes in the level of the endogenous atrial natriuretic factor (ANF) on pituitary-adrenocortical activity, the secretion of corticotropin (ACTH) and corticosterone was studied under the conditions of enhanced and decreased circulating ANF levels in rats. Volume expansion (intravenous infusion of 5 ml of saline within 2 min) induced significant elevation in ANF levels 5 min after the infusion, whereas ACTH levels remained unchanged during the first 20 min and were elevated only at 40 min, i.e. at the time when ANF levels were again normal. Water deprivation for 48 h resulted in decreased ANF levels and increased corticosterone concentrations. ANF concentrations in peripheral blood obtained under thiopental anesthesia were lower than those in blood sampled in the same rats in conscious state. However, such changes were not observed in water deprived animals. In addition, ANF was found to be present in the hypophysial portal blood of anesthetized rats. In conscious sheep, portal ANF levels were significantly higher than those in peripheral blood. Our results support the suggestion of an inhibitory role of ANF in the control of ACTH release and indicate that this role of ANF is physiologically relevant.

Adrenocorticotropic Hormone↗
PubMed1993

Effect of excitatory amino acid on the hypothalamo-pituitary-adrenal axis in the rat during the stress-hyporesponsive period.

During the postnatal period from day 2 to day 10 of life, basal and stress-induced adrenocorticotropic hormone (ACTH) and corticosterone releases are low as compared with adults. This period has been called the 'stress-hyporesponsive period', and its mechanisms are yet undetermined. In this study, we have tested the effects of substances excitatory to neuronal activity on the hypothalamic-pituitary-adrenal (HPA) axis. In 7-day-old rats, administration of the excitatory amino acid (EAA) agonists N-methyl-D,L-aspartic acid (NMA), quisqualic acid, and kainic acid (KA) induced a large increase in plasma ACTH and corticosterone concentrations. All three EAA induced a rapid and potent stimulation of ACTH release within 30 min, the effect on corticosterone secretion being weaker. KA was the more potent EAA, followed by NMA and quisqualic acid. The effect of NMA on the HPA axis was inhibited by pretreatment with a competitive antagonist to N-methyl-D-aspartic acid receptors, D,L-2-amino-5-phosphonovaleric acid. We next sought to determine which level of the HPA axis was affected by EAA administration. Several EAA (glutamic acid, N-methyl-D-aspartic acid, and KA from 10(-5) to 10(-2) M) had no stimulating action on ACTH release from 7-day-old anterior pituitary glands incubated in vitro. In vivo, the stimulating effect of NMA and KA on in vivo ACTH release was blocked after passive immunization with an anti-corticotropin-releasing hormone antiserum, but not after injection of an anti-arginine vasopressin antiserum.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1993

Passive immunization and hypothalamic peptide secretion.

Passive immunization is a common approach used to eliminate the biological activity of an endogenous substance by its binding to a specific antibody (Ab). Surprisingly little information has been gathered on the mechanisms involved. Moreover, the possibility that immunoneutralization could affect also the secretion of the antigen itself has been mostly ignored. To study hypothalamic neuropeptide secretion under the condition of passive immunization, labeled and unlabeled monoclonal antibody (MoAb) against arginine vasopressin (AVP) was injected intravenously. After 2 h a similar amount of 125I-MoAb was found in hypophyseal portal and peripheral (femoral artery) plasma, showing a distribution volume of 73.2 ml/kg. Assessment of the MoAb dilution in the same plasma samples from the binding studies revealed substantially higher dilutions (800-5,700 ml/kg). Such a MoAb dilution (saturation) would be attained by the binding of 130-290 pmol AVP/ml plasma. The calculated amount of plasma AVP decreased by one half within the interval from 2 to 24 h after Ab injection, similarly as did the 125I-MoAb content. Intravenous injection of polyclonal corticotropin-releasing hormone (CRH) Ab resulted in a decrease of plasma adrenocorticotropin and corticosterone levels. After 24 h the dilution of the Ab in portal plasma exceeded two times that in peripheral plasma. CRH concentrations of 0.6-2.5 pmol/ml were found by specific radioimmunoassay after its dissociation from the Ab in plasma. The CRH concentration was higher in portal than in peripheral plasma and was related to the amount of the Ab injected. CRH mRNA levels in the paraventricular nucleus were significantly increased in CRH Ab as compared with normal rabbit serum injected rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Neostigmine stimulates growth hormone-releasing hormone release into hypophysial portal blood of conscious sheep.

GH secretion is stimulated by the administration of cholinesterase inhibitors (such as pyridostigmine and neostigmine) in several species, including man. On the basis of indirect experiments, it has been postulated that this action is mediated by a decrease in hypothalamic somatostatin release. We have investigated the effect of neostigmine in sheep, since it is possible to collect hypophysial portal blood for GH-releasing hormone (GHRH) and somatostatin determination in this species under a conscious unstressed state. First, after i.v. injection of neostigmine (1 mg), a significant increase in plasma GH levels and an unequivocal potentiation of the GH response to GHRH were observed. Then, we observed that i.v. injection of neostigmine (1 mg) induced an immediate, short-lasting (30 min), and marked increase in GHRH (126.1 +/- 17 vs. 14.5 +/- 2.1 pg/ml; P < 0.01) levels in hypophysial portal blood of rams chronically implanted with perihypophysial cannulae. No change in somatostatin secretion was recorded during the same period. These data suggest that the stimulating effect of cholinergic drugs on GH secretion is mediated by stimulation of GHRH release. A direct effect of neostigmine at the level of pituitary gland is possible and may explain the potentiation of GHRH-induced GH release.

Animals↗
PubMed1993

[Stress. Neuroendocrine aspects].

All kind of stress produce an endocrine response. These hormonal responses can serve as stress indicators. The main peripheral endocrine responses to stress are the activation of adrenal corticoids, the stimulation of Growth Hormone (GH) and prolactin secretion, and the inhibition of insulin and gonadal secretion. Except for the inhibition of insulin release, all these hormonal variations depend on the adenohypophysis activity: stimulation of Adrenocorticotrophin hormone (ACTH), GH and prolactin, and inhibition of gonadotrophins (LH-FSH) secretions. Several lines of evidence demonstrate that specific hypothalamic Neuro-hormones stimulate or inhibit the hypophysial activity in response to stress. However, due to methodological difficulties, only measurements of peripheral hormones can be used as stress indicators.

Adrenocorticotropic Hormone↗
PubMed1992

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↗
PubMed1992

Effect of diabetes on in vivo and in vitro hypothalamic somatostatin release.

In order to better understand the mechanisms underlying the reduction in growth hormone (GH) secretion in diabetic rats, we studied hypothalamic somatostatin secretion both in vivo (into hypophysial portal blood) and in vitro (from hypothalamic fragments) 5, 9 and 30 days after induction of diabetes. Experimental diabetes was induced by an intraperitoneal injection of streptozotocin (STZ) at a dose of 65 mg/kg. Basal plasma GH was significantly reduced in diabetic rats at all stages. Somatostatin levels in hypophysial portal blood was unaffected in 5-day STZ-diabetic rats and significantly increased 9 days after STZ administration. Chronic insulin replacement therapy in diabetic animals partly normalized somatostatin levels as well as plasma GH and glucose levels. A good correlation was observed between in vivo and in vitro experiments. Indeed, somatostatin release from hypothalamic fragments did not change 5 days after STZ-induced diabetes and significantly increased 9 and 30 days after STZ administration. The in vitro increase in hypothalamic somatostatin secretion was observed in 10 as well as in 33 mM glucose concentration in the incubation medium. In the same experiment, the in vitro hypothalamic corticotropin-releasing factor secretion was lowered 5 and 9 days after diabetes induction. We conclude that hypothalamic somatostatin release increases in diabetic rats. These changes may contribute to the reduction in GH secretion in these animals. However, since these changes occur after the onset of plasma GH decrease, a factor(s) other(s) than somatostatin may play a causal role in the reduction in GH secretion.

Animals↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1990

Serotonin synthesis from tryptophan by hypothalamic cells in serum-free medium culture.

The hypothalamus of both adult and fetal rats contains a population of cells which can exhibit some features of serotoninergic (5-HT) neurons under certain circumstances. However, their neuronal serotoninergic nature is still controversial. In fact the presence of tryptophan hydroxylase activity has not yet been clearly established. This study attempted to verify whether [3H]5-HT can be synthesized from [3H]tryptophan ([3H]TRP) in hypothalamic cell cultures from 16-day-old fetuses. Data showed that [3H]5-HT was synthesized from [3H]TRP and the amounts of [3H]5-HT increased linearly as a function of time for 60 min. Pargyline markedly increased the quantities of [3H]5-HT and decreased those of [3H]5-hydroxyindole acetic acid. [3H]5-HT synthesis was inhibited by p-chlorophenylalanine, while alpha-methyl-p-tyrosine had no effect. The present biochemical study shows the presence of an intrinsic 5-HT neuronal system in the hypothalamus of the fetal rat.

Animals↗