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Biomedical subjects

A Dutour

Publications and source records attributed to A Dutour.

At least 37 records · Page 2Linked to original sources
PubMed1997

Species differences between male rat and ram pituitary somatostatin receptors involved in the inhibition of growth hormone secretion.

The sheep is a valuable model in which to study GH neuroregulation as its pattern of GH secretion is very close to that in humans. Furthermore, important differences in somatostatin (SRIH) action between rats and sheep have been found previously. Our goal was to compare in male rat and ram pituitaries the binding characteristics of somatostatin receptors and the effect of SRIH and 17 analogues on GH release. Using radioautography, SRIH binding was seen to be evenly distributed over the anterior pituitary of both species. In the binding assay, binding sites were three times more concentrated in rats than in sheep. Important interspecies differences in the action of SRIH and its analogues were found: they inhibited GH at lower concentrations in rats than in sheep. Seven peptides displayed greater inhibitory ability in sheep than in rats while three were more potent in rats. Agonistic potencies to inhibit GH release in rats were correlated with somatostatin receptors subtype 2 (sst2) affinities. Our data confirm and extend the quantitative differences between rat and sheep in SRIH inhibitory action on GH secretion and confirm that ligand-binding properties of a given receptor subtype cannot be extrapolated across species.

Animals↗
PubMed1996

Hormonal response to stress in brittle diabetes.

Acute psychological stress may play a role in the glycaemic instability of some patients with type I diabetes through an increased secretion of insulin-counteracting hormones. To examine the validity of this hypothesis, we subjected to a video-recorded public-speaking stress seven healthy persons, six type I diabetics with stable blood glucose levels and six type I diabetics with unstable or brittle diabetes (with more than 10 hypoglycaemia/month and frequent hyperglycaemia). During the test and on a control day, heart rate, blood pressure, plasma ACTH, cortisol, catecholamines and prolactin were measured. The comparison between the stable and unstable diabetics during the stress session by two-way analysis of variance (group/time) showed a significant difference for heart rate, blood pressure, ACTH and cortisol. Psychological interview showed that most unstable diabetics perceived a link between life stress and their blood glucose control. The unstable patients had much more difficulty in verbalizing their emotions. Our study shows that the two groups of diabetic patients display distinct cardiovascular and neuroendocrine responses to psychological stress, as well as distinct psychological profiles. In conclusion, hormonal response to an acute psychological stress is more pronounced in brittle diabetes and might be one of its pathogenic factors.

Adolescent↗
PubMed1995

Effect of actively immunizing sheep against growth hormone-releasing hormone or somatostatin on spontaneous pulsatile and neostigmine-induced growth hormone secretion.

The physiological role of endogenous circulating GH-releasing hormone (GHRH) and somatostatin (SRIH) on spontaneous pulsatile and neostigmine-induced secretion of GH was investigated in adult rams actively immunized against each neuropeptide. All animals developed antibodies at concentrations sufficient for immunoneutralization of GHRH and SRIH levels in hypophysial portal blood. In the anti GHRH group, plasma GH levels were very low; the amplitude of GH pulses was strikingly reduced, although their number was unchanged. No stimulation of GH release was observed after neostigmine administration. The reduction of GH secretion was associated with a decreased body weight and a significant reduction in plasma IGF-I concentration. In the anti-SRIH group, no changes in basal and pulsatile GH secretion or the GH response to neostigmine were observed as compared to controls. Body weight was not significantly altered and plasma IGF-I levels were reduced in these animals. These results suggest that in sheep, circulating SRIH (in the systemic and hypophysial portal vasculature) does not play a significant role in pulsatile and neostigmine-induced secretion of GH. The mechanisms of its influence on body weight and production of IGF-I remain to be determined.

Animals↗
PubMed1994

Acute stress stimulates secretion of GHRH and somatostatin into hypophysial portal blood of conscious sheep.

The effects of acute stress on growth hormone (GH) secretion and the mechanisms involved in its changes have been investigated in sheep. An acute isolation-restraint stress induced a rapid and significant increase in jugular GH levels in 12 out of 14 rams. GH-releasing hormone (GHRH) and somatostatin secretion during the same stress were studied in 5 animals prepared for hypophysial portal blood collection. A 3.5-fold increase in portal GHRH levels was observed concomitantly with a slight elevation in portal somatostatin. Portal corticotropin-releasing hormone (CRH) and jugular cortisol plasma levels increased during the same stress. Our data suggest that an isolation-restraint stress stimulates GH secretion in the sheep and that GHRH may be responsible for GH response.

Analysis of Variance↗
PubMed1994

Effect of tianeptine on the hypothalamic somatotropic axis in the conscious sheep.

The action of serotonin on growth hormone (GH) secretion is controversial because of interspecies differences and lack of specificity of serotoninergic drugs. Serotonin (5-HT) appears to inhibit GH release in the sheep and in man. We have investigated the site of action of tianeptine, a 5-HT uptake enhancer, in sheep since it is possible to collect hypophysial portal blood for the simultaneous determination of growth hormone-releasing hormone (GHRH) and somatostatin in this species under conscious, unstressed conditions. Tianeptine injection (10 mg/kg i.v.) resulted in a significant, immediate and short-lasting (30 min) increase in peripheral GH (+750%; P < 0.01) and hypophysial portal GHRH (+180%; P < 0.01). No change in the secretion of somatostatin was recorded during the same time. These data suggest that serotoninergic inputs are inhibitory to GH secretion. Tianeptine acts centrally to stimulate GH secretion in the sheep and its effect is mediated through changes in GHRH but not somatostatin release into hypophysial portal blood.

Animals↗
PubMed1994

Relationship between hypophyseal portal GHRH and somatostatin and peripheral GH levels in the conscious sheep.

The mechanisms involved in the genesis of pulsatile GH secretion are not well understood. Recently, methods for hypophyseal portal blood collection in conscious sheep became available. Using this method, GHRH and SRIH secretion into hypophyseal portal blood (HPB) and GH release from the pituitary gland were simultaneous assessed and the relationship between GHRH and SRIH changes in HPB and GH in peripheral blood was investigated. In 23 rams (9-11 month old, 35-45 kg bw), 126 hours of HPB were analysed. Fifty-four spontaneous GH peaks were detected. The majority of GH peaks (48.1%) was associated with an increased portal GHRH and a fall in somatostatin concentrations. A simultaneous increase in GHRH and somatostatin levels was observed in 18.5% of GH peaks while 12.9% of peaks occurred with a fall in SRIH and no modification in GHRH concentrations. Finally, 5/54 (9.3%) GH peaks occurred without any modification in portal GHRH and SRIH release. Our data indicate that the GHRH/SRIH interplay is complex. The occurrence of spontaneous GH peaks may be due not only to a coordinate increase in GHRH and reduction in SRIH release similar to male rat, but also to other patterns of GHRH/SRIH secretion.

Animals↗
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

Pancreastatin-like immunoreactivity in the pancreas of newborn rats.

Pancreastatin (PST), a novel COOH-terminally alpha-amidated peptide is a part of Chromogranin A molecule. Precursor processing implies also the final amidation step dependent on peptidylglycine alpha-amidating monooxygenase (PAM). High activity of PAM as well as Thyroliberin (TRH, another alpha-amidated peptide) concentration and biosynthesis were reported to be very high in neonatal rat pancreas. We followed the concentration of PST-like immunoreactivity in rat pancreas during ontogenesis. High perinatal PST concentration, resembling that of previously reported for PAM activity and TRH concentration was found. These findings suggest that perinatal PAM activation may affect a broader spectrum of pancreatic peptides.

Aging↗
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↗