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J Epelbaum

Publications and source records attributed to J Epelbaum.

At least 127 records · Page 7Linked to original sources
PubMed1989

Involvement of central somatostatin in the alteration of GH secretion in starved rats.

In order to determine the central or peripheral origin of the starvation-induced modifications of growth hormone (GH) and thyroid-stimulating hormone (TSH) secretions, the effects of starvation were studied in freely moving male rats with hypothalamo-hypophyseal disconnection. Five days after the disconnection GH secretion exhibited lower maximal values and higher trough levels and ultradian pulsatile secretion was lost as compared to controls. TSH levels were also decreased. The lesion did not modify pituitary somatostatin (SRIF) receptors as assessed by 125I-Tyr-O-D-Trp-8-SRIF binding or inhibition of adenylate cyclase activity. On the other hand, the growth hormone releasing factor (GRF) capacity to stimulate adenylate cyclase was strongly reduced by the lesion without modification of the affinity. Exposure to 72 h food deprivation decreased GH pulses and TSH levels in control rats but did not modify GH secretory profiles or TSH levels of lesioned rats. Plasma glucose and insulin levels were equally decreased after fasting in control and lesioned rats. Altogether, our results demonstrate that starvation-induced modifications of GH and TSH secretions are of central origin while glucose and insulin changes are peripherally triggered. They suggest that the hypothalamus is the only source of SRIF implicated in this effect.

Adenylyl Cyclase Inhibitors↗
PubMed1988

Displaceable somatostatin binding sites in the gray matter and pyramidal paths of the human developing spinal cord.

The binding of the somatostatin analogue, 125I-iodo-Tyr-[Tyr0,D-Trp8]S14, to the foetal (18- and 24-week-old) and infant (newborn and 17-month-old) spinal cord was examined using in vitro autoradiography. Somatostatin binding sites were detected at cervical, thoracic and lumbosacral levels in foetal as well as in infant spinal cord. The radiolabelling was localized over the grey especially in the superficial layers of the dorsal horn including the substantia gelatinosa and the marginal zone. In foetal and newborn spinal cord, the direct and crossed pyramidal paths exhibited a substantial binding of the ligand. A similar labelling was not observed in the pyramidal paths of a 17-month-old child or in anencephalic newborn spinal cord or previously described in adult. These results emphasize the early presence of somatostatin binding sites during the ontogeny of the human spinal cord. Further, the transient appearance of somatostatin binding sites in the pyramidal paths, prior the myelination, raises the question whether somatostatin receptors could be involved in the maturation of certain normal paths.

Aging↗
PubMed1988

Somatostatin concentrations and binding sites in human frontal cortex are differentially affected in Parkinson's disease associated dementia and in progressive supranuclear palsy.

Somatostatin (SRIF) binding sites were characterized in membrane preparations from post mortem human brain tissues using 125I-Tyr0-D-Trp8-SRIF as a ligand. Density of binding sites were high in subiculum and cortex, moderate in temporal cortex, hippocampal formation and hypothalamus and low in putamen. No correlation was observed with the regional distribution of SRIF levels as measured by RIA. Pharmacological characterization, in frontal cortex preparations, revealed that 125I-Tyr0-D-Trp8-SRIF binding was heterogenous and fitted best with a two sites model. 125I-Tyr0-D-Trp8-SRIF binding was guanine nucleotide dependent. Cortical 125I-Tyr0-D-Trp-8-SRIF binding was not different from controls in non-demented or demented parkinsonians and in patients with progressive supranuclear palsy. On the contrary, SRIF levels were significantly decreased in demented parkinsonians.

Aged↗
PubMed1988

Influence of starvation on hormonal control of hypophyseal secretion in rats.

The reduction of hypophyseal hormone secretion during starvation is not completely understood. A previous study showed that the concomitant reduction of plasma TSH and T3 may be related to an increased sensitivity of the thyrotrope cell to T3. This suggests that regulation of hypophyseal secretion by peripheral hormones may be altered in starved rats. As GH and PRL secretion are under the control of thyroid and steroid hormones, the aim of the present study was to investigate the modification of feed-back control by T3 or E2 on hypophyseal secretion during starvation. For this purpose, pituitary GH, PRL and TSH contents and their plasma responses to TRH injection were measured in euthyroid, thyroidectomized (Tx), T3-supplemented Tx and E2-treated male Wistar rats before and after a 3-day starvation. TRH (0.25 micrograms/100 g) was injected iv through a chronically-implanted catheter. Our results show that GH content and GH plasma response to TRH are dramatically increased in T3-treated Tx starved rats, suggesting that starvation also increases the effectiveness of T3 influence on somatotrope cell secretion. By contrast, effects of T3 on PRL secretion remain unchanged during starvation. Furthermore, starvation in E2-treated rats is associated with a marked rise in the PRL and GH responsiveness to TRH without any significant change of hormonal pituitary content. This suggests that, in starved rats, E2 increases the effects of TRH on lactotrope and somatotrope secretion. No significant effect on TSH secretion could be demonstrated. Thus, starvation seems to act differentially on the feed-back mechanisms controlling the hormonal secretion of the three adenohypophyseal target cells to TRH.

Animals↗
PubMed1987

Somatostatin receptors on cortical neurones and adenohypophysis: comparison between specific binding and adenylate cyclase inhibition.

Primary cultures of mouse embryonic neurones from the cerebral cortex and rat pituitary membranes were used to identify and characterize further the somatostatin receptors coupled to an adenylate cyclase and to compare these receptors with specific binding sites for a non-reducible somatostatin analog. 125I-CGP 23996 on both tissues. 125I-CGP 23996 bound specifically to a single population of sites on cortical neurones and pituitary membranes, with a high affinity (Kd = 2.76 and 1.95 nM respectively). The rank order of potency of somatostatin-(1-14) and some analogs (somatostatin-28, [D-Trp8,D-Cys14]somatostatin-(1-14), native CGP) to displace 125I-CGP 23996 from its binding sites was similar on both tissues. Furthermore this rank order was also found identical for the inhibition of adenylate cyclase activity on cortical neuronal and pituitary membranes. Finally a good correlation was found between the order of potencies of somatostatin analogs evaluated from binding experiments and adenylate cyclase assays, suggesting the presence of the same receptor observed under two different affinity states. According to the classification of somatostatin receptors by Tran and his colleagues (1985) these results support the hypothesis that SSA is the somatostatin receptor coupled with an adenylate cyclase.

Adenylyl Cyclase Inhibitors↗
PubMed1987

Brain somatostatin concentrations do not decrease in progressive supranuclear palsy.

The concentrations of somatostatin and choline acetyl transferase (CAT) were measured in nine brains from patients with progressive supranuclear palsy (PSP) and compared with those obtained from 19 matched control brains. In PSP, CAT activity was reduced in the caudate nucleus and limbic areas (amygdala, hippocampus and cingulate cortex) but was not different from controls in neocortical areas (frontal and temporal). Somatostatin concentrations were not different from controls in any region tested. In contrast to Alzheimer's disease and Parkinson's disease, intellectual deterioration in PSP is not associated with a deficit in neocortical somatostatin and CAT levels.

Aged↗
PubMed1987

Somatostatin receptors on pituitary somatotrophs, thyrotrophs, and lactotrophs: pharmacological evidence for loose coupling to adenylate cyclase.

Pharmacological characterization of somatostatin (SRIF) receptors located on somatotrophs, thyrotrophs, and lactotrophs was attempted by measuring the effects of 14 structural agonists of somatostatin (SRIF) on the inhibition of basal and GRF-stimulated GH and basal and TRH-stimulated PRL and TSH secretion. We also checked the abilities of the analogs to displace [125I]N-Tyr-SRIF binding to pituitary cell membranes and their potency to inhibit adenylate cyclase activity. There was a very good correlation (r = 0.975) between the displacement of [125I]N-Tyr-SRIF and the inhibition of adenylate cyclase activity by the analogs. The effects of the analogs on secretion of the three hormones followed the same rank order of potency. However, the active analogs displayed 2-6 times lower affinities in inhibiting PRL than GH or TSH secretions. The shift in affinity was even more pronounced in the case of the lower potency of the analogs as inhibitors of adenylate cyclase activity compared to hormone secretions. Pretreatment of the cells with pertussis toxin (100 ng/ml; 24 h) blocked SRIF inhibition of basal and GRF-stimulated adenylate cyclase activity and decreased by 83% [125I]N-Tyr-SRIF binding. It also blocked the ability of SRIF to inhibit GRF-induced GH and TRH-induced PRL and TSH secretion. However, pertussis toxin also increased GRF stimulation of GH secretion and decreased TRH stimulation of both TSH and PRL secretion. We conclude from our data that SRIF-binding sites located on the three target cells of the adenohypophysis are of a single class. These binding sites are negatively coupled to adenylate cyclase, but the inhibition of hormone secretions by SRIF cannot be explained solely through adenylate cyclase inhibition. Another mechanism of transduction must be involved in the actions of SRIF on its three pituitary target cells.

Adenylyl Cyclases↗
PubMed1986

Modifications in the cortical regional distribution of choline acetyltransferase, somatostatin and somatostatin binding sites in the normal rat and following lesion of the nucleus basalis.

The regional distribution of choline acetyltransferase activity, somatostatin levels and 125I-CGP 23996 (a somatostatin agonist analog) specific binding sites in 10 separate zones of the cerebral cortex was analyzed. The study was performed in normal rats as well as 15 days after unilateral excitotoxic lesion of the nucleus basalis. A significant correlation was found in the controls between the regional distribution of choline acetyltransferase activity and somatostatin concentrations, both most highly concentrated in the piriform and entorhinal cortex. In contrast, the regional density of 125I-CGP 23996 binding sites correlated neither with choline acetyltransferase activity nor with somatostatin levels. Unilateral lesions of the basal forebrain decreased choline acetyltransferase activity in the frontal and parietal cortex, while 125I-CGP 23996 binding decreased in frontal and occipital regions. No decrease in somatostatin content was observed. The results suggest that, in rats, cortical somatostatin receptors could be associated with cholinergic afferents from the nucleus basalis in the frontal cortex only.

Animals↗
PubMed1986

Angiotensin II and dopamine modulate both cAMP and inositol phosphate productions in anterior pituitary cells. Involvement in prolactin secretion.

Despite their opposite effects on prolactin secretion, both dopamine and angiotensin II inhibit adenylate cyclase activity in homogenates of anterior pituitary cells in primary culture. Dopamine and angiotensin II inhibition of adenylate cyclase was not additive, suggesting that both neurohormones inhibit the adenylate cyclase of the lactotroph cells. Pretreatment with Bordetella pertussis toxin (islet activator protein) completely suppressed the dopamine-induced inhibition of both adenylate cyclase and prolactin secretion. The islet activator protein also reversed the angiotensin II-induced inhibition of the adenylate cyclase activity. In contrast, angiotensin II stimulation of prolactin release was not affected by the toxin. Angiotensin II also induced a dose-dependent stimulation of inositol phosphates (250%) with an EC50 of 0.1 nM, close to that observed for prolactin secretion. Islet activator protein pretreatment did not block the stimulation of inositol phosphate production. Dopamine inhibited the angiotensin II-stimulated prolactin release and the production of inositol phosphates induced by angiotensin II. It is concluded that angiotensin II and dopamine receptors of lactotroph cells are able to modulate both cAMP and inositol phosphate production. The dopamine receptor of lactotrophs appears to be the first example of a receptor which is negatively coupled to the production of inositol phosphates.

Adenosine Diphosphate Ribose↗
PubMed1986

Somatostatin in the central nervous system: physiology and pathological modifications.

Since its discovery, at the beginning of 1973, somatostatin's multiple actions, in relation to its wide anatomical distribution have been widely documented. Its biochemical pathways have been elucidated with the discovery of other molecular forms as well as the mechanisms of its neuronal release. However, no definite proof is available concerning a neurotransmitter role for any peptide of the somatostatin family other than somatostatin-14. The precise determination of the roles of somatostatin in brain are still hampered by the poor pharmacology of the peptide. New tools are badly needed and in particular a true antagonist at the receptor site. The mechanisms of action of somatostatin are now well under way at least in the pituitary model. More information should come from this model and be applied to brain cells in vitro. The greatest challenge of somatostatin brain function lies in its role in the pathophysiology of neurological diseases such as Alzheimer's dementia and Huntington's disease. Nature has been using somatostatin-related molecules since inhibitory control was first needed in cell functions. Time will tell us if somatostatin is really an old peptide involved in senile dementia.

Adenoma↗
PubMed1986

Somatostatin and regulation of prolactin secretion.

In addition to its classical growth hormone (GH) inhibiting action, somatostatin (SRIF) inhibits prolactin (PRL) secretion in man and rat under specific endocrine conditions. Furthermore, SRIF counteracts the thyrotropin releasing hormone (TRH) and vasoactive intestinal peptide (VIP) stimulated prolactin release from rat adenohypophysis in vitro. Two criteria are needed to demonstrate a physiological role of SRIF in PRL control: specific receptors must be present on prolactin secreting cells, and antagonization of endogenous SRIF must affect PRL secretion in vitro. In fact [125I]N--Tyr--SRIF binds to membranes not only of human GH-secreting adenomas, but also of prolactinomas. Specific binding characteristics are comparable in both cell types, but the density of sites in PRL-secreting adenomas is only one-quarter that in GH-secreting adenomas. In contrast, non-PRL-secreting chromophobe adenomas are devoid of specific binding. On the other hand, administration of SRIF antisera (SRIF-AS) affects both GH and PRL secretion in starved rats (a model in which pulsatile GH secretion is abolished); a marked increase in PRL plasma levels occurs, but the needed SRIF-AS concentration is higher than that for GH disinhibition. This demonstrates that endogenous SRIF may exert a negative control over PRL secretion, although lactotroph cells appear less sensitive to SRIF than somatotrophs. Since the apparent affinity of SRIF binding sites is similar on both GH and PRL secreting cells, at least in human tumor tissues, a lower density of SRIF receptors on PRL cells could account for this reduced responsiveness. Alternatively, different coupling mechanisms may be involved in the two cell types.

Adenoma↗
PubMed1986

Involvement of endogenous somatostatin in the regulation of thyrotroph secretion during acute and chronic changes in diet.

The aim of this study was to investigate the involvement of somatostatin (SRIF) in the thyrotroph adaptation to nutritional changes. For this purpose, we studied the effects of passive immunization with SRIF antiserum (A-SRIF) on the reduced basal TSH secretion in rats starved for 72 h and on the plasma TSH surge following carbohydrate (CHO) refeeding. This latter experiment was performed at two different times of the day in order to elucidate whether SRIF may participate in the regulation of the plasma TSH circadian rhythm. In chronically catheterized rats, we observed that A-SRIF injection induced a similar pattern of plasma TSH rise over a sampling period of 5 1/2 h in both fed and rats starved for 72 h (3-way analysis of variance). In morning experiments, CHO refeeding or A-SRIF injection elicited a significant rise in plasma TSH. The amplitude and duration of the response was proportional to the injected dose. In evening experiments, although basal TSH values were significantly lower than those observed in the morning ones, maximal plasma TSH values after A-SRIF injection were not significantly different. At both times of the day, association of refeeding and A-SRIF injection did not stimulate TSH further than either refeeding alone or A-SRIF alone. In conclusion, our data suggest that SRIF cannot account for the differences in serum TSH levels between fed and starved rats; is not responsible for the diurnal difference in basal serum TSH in starved rats, and seems to be involved in the TSH response to refeeding.

Animals↗
PubMed1986

The anterior periventricular hypothalamus is the site of somatostatin inhibition of its own release: an in vitro and immunocytochemical study.

The site of action of the inhibitory effect of somatostatin (SRIF) on its own release was studied by: (1) measuring SRIF release in vitro from tissue preparations containing either the proximal (periventricular hypothalamus) or the distal (median eminence) portions of the hypothalamic SRIF neurons, and (2) immunocytochemical investigation of the interconnections occurring between SRIF neuronal elements in these hypothalamic regions. In vitro, a biologically active, but noncross-reacting SRIF analog (D-Trp8 SRIF) in the RIA, inhibited 25 mM K+ induced SRIF release from anterior periventricular hypothalamic tissues. The inhibitory effect of D-Trp8 SRIF was dose-dependent, maximal at 10(-7) M, and restricted to this anterior region, since median-eminence SRIF release was not modified by the presence of D-Trp8 SRIF. Additionally, LHRH release from anterior periventricular hypothalamus was unchanged in the presence of D-Trp8 SRIF. In the periventricular nucleus, perikarya and dendrites of labeled SRIF neurons showed frequent apposition of their limiting membranes. Classical synapses were also observed between SRIF-containing axonal processes and labeled perikarya or dendrites. Although membrane appositions between neighboring SRIF axons frequently occurred in the median eminence, no synaptic-like SRIF-SRIF connections could be detected at this level. The data demonstrate a direct inhibitory action of a SRIF agonist on the anterior periventricular hypothalamic release of the peptide. This effect correlates well with the occurrence of SRIF-SRIF synapses in this region; suggesting that SRIF exerts a negative feedback in the control of its own release through autoreceptors located on the perikarya or dendrites of SRIF-containing neurons.

Animals↗
PubMed1986

Sensitivity of thyrotropin (TSH) secretion to 3,5,3'-triiodothyronine and TSH-releasing hormone in rat during starvation.

The mechanisms by which plasma T3 and TSH decrease after a 3-day starvation period are not completely understood. In this study we tested the hypothesis of a possible modification in the sensitivity of thyrotroph cell to T3 and/or TRH. For that purpose, TRH tests were performed before and after a 3-day starvation in euthyroid, thyroidectomized, and T3-treated (75 or 175 ng/100 g BW) thyroidectomized male Wistar rats. TRH (10 to 500 ng/100 g BW) was injected iv through a chronically-implanted catheter. In another set of experiments, hypophyseal TSH content was also determined. Our results showed that after a 3-day-starvation plasma TSH decreased in all except hypothyroid rats; TSH responsiveness to TRH was unchanged in euthyroid rats but was increased in hypothyroid rats; and the T3-dependent increase in TSH responsiveness to TRH was significantly amplified. Moreover, there was a significant positive correlation between TSH responsiveness to TRH and hypophyseal TSH content. These results suggest that starvation induces an increased sensitivity of thyrotroph cell to T3.

Animals↗
PubMed1986

Differential effects of passive immunization with somatostatin antiserum on adenohypophysial hormone secretions in starved rats.

The role of somatostatin (SRIF) on adenohypophysial hormone secretion in starved rats was reassessed by passive immunization. Because of the absence of pulsatile GH secretion in starved rats, the effects of the injection of SRIF antiserum on GH levels can be clearly demonstrated. To determine whether starvation modifies the sensitivity of the adenohypophysis to SRIF, we measured 125I-labelled iodo-N-Tyr-SRIF binding. There was no difference in the dissociation constant (Kd) nor in the maximal binding capacity (Bmax) in fed (n = 15) and starved (n = 15) animals (Kd = 0.38 +/- 0.09 (S.E.M.) and 0.45 +/- 0.09 nmol; Bmax = 204 +/- 39 and 205 +/- 30 fmol/mg protein respectively). Administration of SRIF antiserum resulted in a dose-dependent increase in plasma concentrations of GH, TSH and prolactin. The minimal effective dose of SRIF antiserum was 50 microliters for GH, 100 microliters TSH and 200 microliter for prolactin. Our results show that: starvation does not modify adenohypophysial SRIF-binding sites, in starved male rats endogenous SRIF exerts a negative control on prolactin secretion in vivo and sensitivity to endogenous SRIF seems to be different for each hypophysial cell type.

Animals↗