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M T Bluet-Pajot

Publications and source records attributed to M T Bluet-Pajot.

At least 19 recordsLinked to original sources
PubMed2001

In vivo internalization of the somatostatin sst2A receptor in rat brain: evidence for translocation of cell-surface receptors into the endosomal recycling pathway.

To determine whether cellular compartmentalization of somatostatin receptors can be regulated in vivo, we examined the immunocytochemical distribution of the sst2A receptor (sst2AR) after stereotaxical injections of somatostatin analogs into the rat parietal cortex. Whereas CH-275, a sst1R agonist, failed to induce changes in the diffuse sst2AR immunostaining pattern characteristic of control animals, somatodendritic profiles displaying intracytoplasmic immunoreactive granules became apparent short-term after injection of either somatostatin or the sst2R agonist octreotide. Confocal microscopy revealed that 90% of sst2AR-immunoreactive endosome-like organelles displayed transferrin receptor immunoreactivity. At the electron microscopic level, the percentage of sst2AR immunoparticles dramatically decreased at the plasmalemma of perikarya and dendrites after octreotide injection. Conversely, it significantly increased in endosomes-like organelles. These results demonstrate that sst2ARs undergo, in vivo, rapid and massive internalization into the endocytic recycling compartment in response to acute agonist stimulation and provide important clues toward elucidating somatostatin receptor signaling in the mammalian brain.

Animals↗
PubMed2001

In vivo and in vitro effects of ghrelin/motilin-related peptide on growth hormone secretion in the rat.

Ghrelin (Ghr), a 28 amino acid gastric peptide with an n-octanoylation on Ser 3, has recently been identified as an endogenous ligand of the growth hormone secretagogue (GHS) receptor. A cDNA was also isolated from a mouse stomach library encoding a protein named prepromotilin-related peptide (ppMTLRP) which shares sequence similarities with prepromotilin. Mouse and rat ppMTLRP sequences (rGhr) are identical and show 89% identity with human ghrelin (hGhr). By analogy with promotilin, cleavage of proMTLRP into an 18 amino acid endogenous processed peptide can be assumed on the basis of a conserved dibasic motif in position 9-10 of its sequence. In the present work, we compared the GH-releasing activity of rGhr28/MTLRP and of hGhr28/MTRLP with that of a shorter form of the peptide, hGhr18. A short peptide devoid of Ser-3 n-octanoylation hGhr18[-] was also tested. Addition of rGhr28, hGhr28 and hGhr18 stimulated GH release to the same extent from superfused pituitaries. The effect was dose dependent in a 10(-8) to 10(-6) M concentration range. In contrast, hGhr 18[-] was inactive. In freely moving animals, both rGhr28 and hGhr28 (10 microg, i.v.) stimulated GH release, whereas the same dose of hGhr18 or of hGhr18[-] was ineffective. After rGhr28, GH plasma levels increased as early as 5 min after injection and returned to basal values within 40-60 min. Expressed as percent stimulation, administration of rGhr28 was equally effective when injected during troughs or peaks of GH. Plasma concentrations of prolactin, adrenocorticotropin and leptin were not modified. Spontaneous GH secretory episodes were no longer observed within 3 h of rGhr28 treatment, but repeated administration of the secretagogue at 3- to 4-hour intervals resulted in a similar GH response. Activation of somatostatin (SRIH) release by ether stress did not blunt the GH response to rGhr28. This suggests that the secretagogue acts in part by inhibiting endogenous SRIH, as further substantiated by the ability of rGhr28 (10(-6) M), to decrease the amplitude of 25 mM K+-induced SRIH release from perifused hypothalami. In conclusion, (1) n-octanoylation of Ghrs and the shorter form hGhr18 is essential for the direct pituitary GH-releasing effect of this new family of endogenous GHSs; (2) only the longer forms are active in vivo and (3) inhibition of SRIH release appears involved in the mechanism of Ghr action.

Adrenocorticotropic Hormone↗
PubMed2001

Growth hormone secretagogues and hypothalamic networks.

Growth hormone secretagogues (GHSs) act at distinct levels to control growth hormone (GH) secretion. At the pituitary level they reinforce or extend a tonic GH-releasing-hormone (GHRH)-induced activated state by mobilizing intracellular Ca2+ store. At the hypothalamic level GHS actions are more complex than originally anticipated. Chronic treatments with GHS result in loss of responsiveness to the secretagogues, an effect probably accounted for by indirect negative feedback of GHS stimulated plasma GH levels over GHRH release. Moreover, intracerebroventricular treatments with GHS can have paradoxical, inhibitory effects on GH secretion. Several mechanisms can account for such dual effects. GHS receptors were found to extend far beyond the arcuate nucleus and are mainly coexpressed by GHRH, somatostatin, and neuropeptide Y (NPY) neurons. Activation of GHRH neurons by GHS can be direct or indirect. Indeed using antisense strategy we found that sstl are physiological activators of arcuate GHRH neurons and we propose that activation of SRIH arcuate interneurons by GHS can increase GHRH neuron activity. Moreover, GHS can stimulate distinct populations of NPY neurons having opposite effects on GH secretion: arcuate NPY interneurons, act as indirect facilitators of GHRH release, whereas, on the contrary, a different subset of NPY neurons projecting to the periventricular hypothalamus (those also involved in mediating leptin effects on GH) seems able to activate SRIH release.

Animals↗
PubMed2000

Involvement of sst2 somatostatin receptor in locomotor, exploratory activity and emotional reactivity in mice.

Somatostatin (SRIF) controls many physiological and pathological processes in the central nervous system but the respective roles of the five receptor isotypes (sst1-5) that mediate its effects are yet to be defined. In the present study, we attempted to identify functions of the sst2 receptor using mice with no functional copy of this gene (sst2 KO mice). In contrast with control 129Sv/C57Bl6 mice, sst2 mRNA was no longer detectable in the brain of sst2 KO mice; 125I-labeled Tyr0DTrp8-SRIF14 binding was also greatly reduced in almost all brain structures except for the hippocampal CA1 area, demonstrating that sst2 accounts for most SRIF binding in mouse brain. Invalidation of this subtype generated an increased anxiety-related behaviour in a number of behavioural paradigms, while locomotor and exploratory activity was decreased in stress-inducing situations. No major motor defects could be detected. sst2 KO mice also displayed increased release of pituitary ACTH, a main regulator of the stress response. Thus, somatostatin, via sst2 receptor isotype pathways, appears involved in the modulation of locomotor, exploratory and emotional reactivity in mice.

Adrenocorticotropic Hormone↗
PubMed2000

Involvement of the Sst1 somatostatin receptor subtype in the intrahypothalamic neuronal network regulating growth hormone secretion: an in vitro and in vivo antisense study.

Five somatostatin (SRIH) receptors (sst1-5) have been cloned. Recent anatomical evidence suggests that sst1 and sst2 may be involved in the central regulation of GH secretion. Given the lack of specific receptor antagonists, we used selective antisense oligodeoxynucleotides (ODNs) to test the hypothesis that one or both of these subtypes are involved in the intrahypothalamic network regulating pulsatile GH secretion. In mouse neuronal hypothalamic cultures the proportion of GHRH neurons coexpressing sst1 or sst2 messenger RNAs (mRNAs) was identical. In contrast, sst1 mRNAs were more often present than sst2 in SRIH-expressing neurons. Firstly, sst1 antisense ODN in vitro treatment abolished sst1, but not sst2, receptor modulation of glutamate sensitivity and decreased sst1, but not sst2, mRNAs. The reverse was true after treatment with sst2 antisense. Sense ODNs did not alter the effects of SRIH agonists. In a second series of experiments, nonanaesthetized adult male rats were infused for 120 h intracerebroventricularly with ODNs. Only the sst1 antisense ODN diminished the amplitude of ultradian GH pulses without modifying their frequency. In parallel, sst1 antisense ODN strongly diminished sst1 immunoreactivity in the anterior periventricular nucleus and median eminence, as well as sstl periventricular nucleus mRNA levels. The effectiveness of the sst2 antisense ODN was attested by the inhibition of hypothalamic binding of [125I]Tyr0-D-Trp8-SRIH. Scrambled ODNs had no effect on GH secretion or on sst mRNAs or SRIH binding levels. These results favor a preferential involvement of sst1 receptors in the intrahypothalamic regulation of GH secretion by SRIH.

Animals↗
PubMed1999

EMK protein kinase-null mice: dwarfism and hypofertility associated with alterations in the somatotrope and prolactin pathways.

Gene trapping was used in embryonic stem (ES) cells in an attempt to inactivate genes involved in development. The Emk (ELKL motif kinase) gene has been disrupted and a mutant mouse line derived. Previous work had shown that EMK kinases, called MARK in the rat, exert a major control on microtubule stability by phosphorylating microtubule-associated proteins and that genes homologous to Emk in yeast or Caenorhabditis elegans are essential for cell and embryonic polarity. Although we found the Emk gene to be active in the preimplantation mouse embryo and then to show a widespread expression, Emk-null mice had no embryonic defect and were viable. They show an overall proportionate dwarfism and a peculiar hypofertility: homozygotes are not fertile when intercrossed, but are fertile in other types of crosses. Insulin-like growth factor I (IGF I) and IGF-binding protein 3 (IGFBP3) were reduced in the plasma of homozygotes of both sexes. A direct implication of the EMK kinase in IGF I plasmatic production is unlikely because the Emk gene does not seem to be expressed in hepatocytes. Nevertheless, GH assayed at arbitrary times in plasma did not show differences between genotypes and GH concentrations in pituitary extracts were not found to be altered in homozygotes. Our results, though, do not exclude the possibility that in the mutants the overall quantity of GH secreted daily is reduced. Our observation of a smaller size of the pituitaries of the mutants is in favor of this hypothesis. The prolactin concentration in the pituitaries was much lowered in homozygous females, but it was normal in males. The possible involvement of EMK protein kinase in hormone secretion in the pituitary and/or the hypothalamus, via the microtubule network, is discussed.

Animals↗
PubMed1998

Hypothalamic and hypophyseal regulation of growth hormone secretion.

1. Regulation of pulsatile secretion of growth hormone (GH) relies on hypothalamic neuronal loops, major transmitters involved in their operation are growth hormone releasing hormone (GHRH) synthetized mostly in arcuate nucleus (ARC) neurons, and somatostatin (SRIH), synthetized both in hypothalamus periventricular (PVe) and ARC neurons. 2. Neurons synthetizing both peptides can inhibit each other in a reciprocal manner. Other neuropeptides synthetized in ARC neurons, such as galanin, or in ARC interneurons, such as neuropeptide Y (NPY), are able to modulate synthesis and release of GHRH and SRIH into the hypothalamohypophyseal portal system. 3. In addition, the hitherto uncharacterized endogenous ligand of the recently cloned growth hormone releasing peptide receptor, expressed mostly in the ARC, triggers GH release, presumably by actions on ARC interneurons. 4. Thyroid, gonadal, and adrenal steroid hormones also affect the GHRH-SRIH balance; a differential distribution of sex steroid receptors in the ARC and the PVe is likely to account for the different pattern of GH secretion in male and female animals. 5. Growth hormone itself is able to inhibit the amplitude of GH secretory episodes and to increase their frequency, by entering the brain (presumably by receptor-mediated internalization at the level of the choroid plexus) and acting subsequently on ARC neurons. 6. At the pituitary level, major neurotransmitters regulating GH cells act on receptors of the VIP/PACAP/GHRH family and of the somatostatin family, in particular, sst2 and sst3. Those are coupled to accumulation of cAMP as a second messenger. 7. In addition, patch-clamp experiments and measurement of intracellular Ca2+ indicate that GH cells present characteristic, GHRH-dependent, but self-maintained Ca2+ spikes and [Ca2+]i transients, which reflect adaptive mechanisms to constraints of episodic release. 8. Recent data on transcription factors affecting GH gene expression and somatotrope differentiation are also summarized. 9. Regulation and differentiation of somatotropes also depend upon paracrine processes within the pituitary itself and involve growth factors and several neuropeptides, for instance, vasoactive intestinal peptide, angiotensin 2, endothelin, and activin. 10. Finally, characteristic changes occur in the GH secretory pattern under discrete, pathological conditions, such as abnormal growth and dwarfism, diabetes, and acromegaly, as well as during inflammatory processes.

Animals↗
PubMed1997

An enzyme immunoassay for rat growth hormone: validation and application to the determination of plasma levels and in vitro release.

A competitive enzyme immunoassay for rat growth hormone (rGH) has been developed using polyclonal anti-rGH antibodies and an acetylcholinesterase (EC 3.1.1.7.) enzymatic tracer coupled covalently with rGH. The assay was performed in 96-well microtiter plates coated with rabbit polyclonal anti-goat immunoglobulin antibodies. Molecular sieve filtration and Western blot analysis revealed a single immunoreactive peak for rat plasma or pituitary extracts. Cross-reactivity with other rat pituitary hormones or human GH was less than 1%. Assay of samples in a concentration range of 0.7 to 69 ng/ml by enzyme immunoassay and radioimmunoassay were well correlated (r = 0.87 and 0.85 respectively for plasma and culture medium samples). Intra- and inter-assay variations in plasma were 4 (n = 24) and 14% (n = 9) respectively. Minimal detectable amounts of rGH were 0.6 ng/ml. A two-site immunometric assay also developed with the same antibodies allowed a detection threshold of 0.25 ng/ml.

Acetylcholinesterase↗
PubMed1997

Intrahypothalamic growth hormone feedback: from dwarfism to acromegaly in the rat.

Two different dwarf rat models with primary (dw/dw, DW) or secondary (transgenic growth retarded, WF/Tgr) GH deficiency and contrasting hypothalamic GH-releasing hormone (GHRH) and somatostatin (SRIH) expression were implanted sc with GC cells. These form encapsulated rat GH-secreting tumors that maintain high plasma rat GH levels for several weeks. In both strains, GC cell tumors stimulated growth and raised GHBP levels, without affecting pituitary GH content. In DW rats, GC cell implants increased SRIH expression in the periventricular nucleus (PeV), but not in the arcuate nucleus (ARC), whereas their high GHRH expression in ARC was decreased by GC cells. In contrast, GC cell implants in WF/Tgr rats had little effect on the already high SRIH expression in PeV or low GHRH expression in ARC, although they reduced SRIH expression in ARC. GC cell implants also reduced GH receptor expression in both ARC and PeV in the WF/Tgr dwarves. Thus, chronic GH overexposure stimulates rapid growth in both dwarf strains, but has differential hypothalamic effects in these models. This experimental approach now makes it possible to study the effects of pathophysiological concentrations of GH ranging from dwarfism to acromegaly in the same animal model.

Acromegaly↗
PubMed1997

Continuous intracerebroventricular administration of a corticotropin releasing hormone antagonist amplifies spontaneous growth hormone pulses in the rat.

Involvement of endogenous corticotropin releasing hormone (CRH) in the regulation of spontaneous growth hormone (GH) secretion was investigated. A CRH antagonist, alpha helical CRH 9-41, was intracerebroventricularly infused for 36 h at a rate of 1 microgram/0.5 microliter/h to freely moving, cannulated adult male rats. Serial blood samples were drawn every 20 min for the last 8 hours of alpha helical CRH 9-41 infusion. The treatment induced a marked increase in GH peak amplitude without affecting either trough levels or numbers of peaks. In parallel, levels of growth hormone releasing hormone (GHRH) mRNA in the arcuate nucleus, but not of somatotropin release inhibiting hormone (SRIH) mRNA in the periventricular and arcuate nuclei, were increased. These data suggest that, in addition to its action in the stress-induced inhibition of GH secretion through regulation of periventricular SRIH neurons, CRH can also act as a modulator of endogenous GH secretion through regulation of arcuate GHRH neurons. Whether the modulatory effects of CRH on GHRH neurons are direct or indirect remains to be established.

Adrenocorticotropic Hormone↗
PubMed1996

Central administration of a growth hormone (GH) receptor mRNA antisense increases GH pulsatility and decreases hypothalamic somatostatin expression in rats.

To test the hypothesis of the involvement of centrally expressed rat growth hormone receptors (rGH-R) in the ultradian rhythmicity of pituitary GH secretion, adult male rats were submitted to a 60 hr intracerebroventricular infusion of an antisense (AS) oligodeoxynucleotide (ODN) complementary to the sequence of rGH-R mRNA. Eight hour (10 A.M.-6 P.M.) GH secretory profiles, obtained from freely moving male rats infused with 2.0 nmol/hr of rGH-R AS, revealed a marked increase in GH peak amplitude (150 +/- 12 vs 101 +/- 10 ng/ml), trough levels (16.2 +/- 3.0 vs 5.4 +/- 1.4 ng/ml), and number of peaks (2.9 +/- 0.3 vs 1.8 +/- 0.2). No change was observed in rats treated with an ODN complementary to the prolactin receptor mRNA sequence (2.0 nmol/hr). Infusion of increasing ODN concentrations resulted in a dose-dependent stimulation of GH release. In parallel, somatogenic binding sites in the choroid plexus were decreased by 40%, and levels of rGH-R mRNA were increased in the periventricular nucleus (PeV) but unchanged in the arcuate nucleus (ARC). Levels of somatostatin mRNA, in the PeV but not in the ARC, were lowered by the treatment. Levels of GH-releasing hormone mRNA in the ARC were not affected. These data suggest that GH negative feedback results from a direct effect on central GH receptors and a subsequent activation of hypophysiotropic somatostatin neurons located in the anterior periventricular hypothalamus.

Animals↗
PubMed1996

Activation of locus coeruleus somatostatin receptors induces an increase of growth hormone release in male rats.

Noradrenergic neurons of the locus coeruleus (LC) negatively regulate the endogenous rhythmicity of growth hormone (GH) secretion. These neurons express high concentrations of receptors for somatostatin (SRIH) and galanin (GAL), two neuropeptides which can affect electrical activity of LC neurons and also centrally modulate plasma GH levels. We thus investigated whether somatostatin and galanin receptors located in the LC are involved in GH regulation. Pulsatile patterns of endogenous GH secretion were monitored after unilateral infusion of the peptides into the lateral ventricle (ICV) or into the LC, after lesion of contralateral LC neurons by 6 hydroxydopamine. Neither unilateral LC lesions nor administration of saline affected GH release. When administered ICV, both SRIH (5 micrograms/microliter/15 min) and GAL (1 microgram/microliter/15 min) resulted in a marked increase in GH secretion. Infusion of SRIH into the LC induced a significant but weaker stimulation of plasma GH as compared to ICV injections. In contrast, infusion of GAL into the LC was ineffective. These results indicate that somatostatin can exhibit direct effects on noradrenergic neurons of the LC involved in GH regulation, whereas central effects of galanin on the hormone are mediated by distinct structures.

Animals↗
PubMed1996

The increase in growth hormone secretion in experimentally induced arthritic rats is an adaptive process involved in the regulation of inflammation.

In Sprague-Dawley rats, Freund-adjuvant-induced arthritis (AIA) results in an increase in the amplitude of ultradian growth-hormone (GH)-secretory episodes without modification of their frequency. This is most apparent at the time of maximal inflammation, i.e. 14-21 days after inoculation of the adjuvant. GH responsiveness to a maximal dose of clonidine (10 micrograms/100 g body weight, BW), a secretagogue known to act at the hypothalamic level, is comparable in AIA and control rats. In contrast, GH response to a maximal dose of GH-releasing hormone (GHRH, 1 microgram/100 g BW), a peptide acting directly on pituitary somatotropes, is greater in AIA than in control rats. Furthermore AIA affects significantly neither hypothalamic somatostatin and GHRH mRNA levels nor pituitary GH content. In adult rats treated neonatally with monosodium glutamate (MSG), a neurotoxin which destroys the majority of GHRH neurons of the arcuate nucleus and reduces considerably plasma GH levels, clinical symptoms observed 14 days after inoculation of the Freund adjuvant are more marked than in AIA. The MSG-treated rats exhibit in particular a significantly higher increase in hindpaw diameter. Pulsatile administration of GH (40 micrograms/day/rat, with successive periods of 2 h of GH and 4 h of mineral oil) restoring the endogenous GH-secretory pattern throughout the 15-day period of arthritis development prevents hindpaw diameter increase. These results indicate that the impact of AIA on GH regulation occurs at the pituitary but not the hypothalamic level and suggest that increased GH secretion observed in AIA rats is an adaptive mechanism involved in the regulation of the inflammatory process.

Animals↗
PubMed1996

Effects of neonatal administration of octreotide, a long-lasting somatostatin analogue, on growth hormone regulation in the adult rat.

The pulsatile pattern of GH secretion slowly develop in the postnatal period concomitantly with the dual network of GHRH and somatostatin (SRIH) hypothalamic neurons. We investigated whether an early postnatal treatment with a long acting SRIH analogue, octreotide, could affect maturation and subsequent operation of those networks in the adult rat. Octreotide administration (5 mu g/rat SC) every other day during the first 10 days of life resulted in growth retardation in the adult. In parallel, the amplitude of plasma GH secretory episodes in free moving unanesthetized animals was markedly reduced. The numbers of arcuate GHRH mRNA-containing and periventricular SRIH-mRNA containing neurons were not affected by the treatment. GHRH mRNA levels per neuron however was decreased by 30%, and median eminence GHRH stores by 50%. SRIH expression in the arcuate nucleus was also diminished, as was the number of 125I-SRIH labeled neurons in that nucleus. The effects of octreotide were compared to the hyposomatotropinemia induced by administration of monosodium glutamate (MSG), every other day during the first 10 days of life. Growth retardation and inhibition of GH secretory episodes in adult rats neonatally treated with MSG were slightly more pronounced than after octreotide. In contrast to octreotide, MSG induced a massive loss of GHRH neurons and a concomitant decrease in 125I-SRIH binding. Somatostatin did not protect GHRH neurons against the neurotoxic action of MSG since octreotide treatment did not further affect any of the parameters impaired by MSG. In conclusion, these experiments demonstrate that neonatally injected octreotide cannot counteract the toxic effect of MSG on arcuate neurons. However, a neonatal treatment with the SRIH agonist affects permanently growth rate and GH pulsatility. This effect is mediated in the hypothalamus by permanently impairing the neural networks that control GH secretion.

Animals↗
PubMed1995

Neuropeptide-E-I antagonizes the action of melanin-concentrating hormone on stress-induced release of adrenocorticotropin in the rat.

The physiological role of melanin-concentrating hormone (MCH) in mammals is still very elusive, but this peptide might participate in the central control of the hypothalamopituitary adrenal (HPA) axis during adaptation to stress. Cloning and sequencing of the rat MCH (rMCH) cDNA revealed the existence of additional peptides encoded into the MCH precursor. Among these peptides, neuropeptide (N) glutamic acid (E) isoleucine (I) amide (NEI) is co-processed and secreted with MCH in rat hypothalamus. In the present work we examined: (1) The pattern of rMCH mRNA expression during the light and dark conditions in the rat hypothalamus and (2) The effect of intracerebroventricular (ICV) injections of rMCH and NEI in the control of basal or ether stress-modified release of corticotropin (ACTH), prolactin (PRL) and growth hormone (GH) secretion in vivo in light-on and light-off conditions. Our data indicate that rMCH mRNA levels do not change during the light-on period, but increase after the onset of darkness. Either alone or co-administered, rMCH and NEI do not modify basal secretion of GH and PRL at any time tested nor do they alter ether stress-induced changes in these two hormonal secretions. At the end of the light on period corresponding to the peak of the circadian rhythm in ACTH, administration of rMCH but not NEI leads to a decrease in ACTH levels while MCH is not effective during the light off period of the cycle (i.e. when basal ACTH levels are already low). Using a moderate ether induced stress, ACTH levels are only stimulated during the dark phase of the cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1995

Effects of chronic octreotide treatment on GH secretory dynamics and tumor growth in rats bearing an ectopic somatotroph (GC) tumor.

The effects of octreotide, a long-acting somatostatin agonist selective of the sstr2/sstr3/sstr5 receptor subtypes, on ectopic GH secretion and tumor growth were investigated in Wistar-Furth female rats implanted with GH secreting (GC) cells which express mostly somatostatin receptors of the sstr1 and sstr2 subtypes. Octreotide dose dependently inhibited thymidine incorporation (-57%) and GH secretion (-41%) from GC cells in culture. In vivo, 6 weeks after GC cell implantation, plasma GH, IGF-1 and insulin levels were highly elevated. Cluster analysis of GH secretory dynamics revealed that GH secretion was less pulsatile in GC-implanted than in control animals. Furthermore, in GC-implanted animals, passive immunization either with SRIH or GHRH antisera, did not affect GH plasma levels. Three weeks after GC cell implantation, when tumors became palpable, octreotide (1 micrograms/h/kg BW) or saline was infused constantly for three weeks by osmotic minipumps. In octreotide treated rats, GH, IGF-1 and insulin levels were not different from sham-implanted animals and tumors weight were reduced by 80%. High affinity somatostatin binding sites were found in equivalent amounts on tumors from octreotide-treated or saline-treated animals. These findings indicate that GH secretion in GC-rats is mainly derived from the tumors and independent of hypothalamic control and that octreotide reduces both GH secretion and tumor growth. We conclude that the GC-implanted rat represents a good animal model to test the antisecretory and antitrophic properties of somatostatin analogs in vivo.

Animals↗
PubMed1995

Neuroendocrine regulation of growth hormone.

This short review is focused on the neuroendocrine regulation of growth hormone (GH) pulsatile secretory pattern and GH gene expression. The neuronal network involved in the central control of GH includes extrahypothalamic neurons such as the noradrenergic and cholinergic systems, which regulate the two antagonistic neurohormonal systems: somatostatin (SRIH) and GH-releasing hormone (GHRH). Intrahypothalamic Proopiomelanocortin- and Galanin-containing interneurons also participate in the regulation of SRIH and GHRH neuronal activity, which also is dependent on sex steroids and GH and/or insulin-like growth factor I (IGF-I) feedback. cAMP (controlled mainly by GHRH and SRIH), thyroid and glucocorticoid hormones. IGF-I and activin are among the factors that regulate GH gene expression at the transcriptional level and may play a role in somatotroph differentiation and proliferation during ontogeny as well as physiological and pathological states such as acromegaly.

Animals↗