Inhibitory Action Of Somatostatin Research Articles

Crosstalks between kisspeptin neurons and somatostatin neurons are not photoperiod dependent in the ewe hypothalamus

Seasonal reproduction is under the control of gonadal steroid feedback, itself synchronized by day-length or photoperiod. As steroid action on GnRH neurons is mostly indirect and therefore exerted through interneurons, we looked for neuroanatomical interactions between kisspeptin (KP) neurons and somatostatin (SOM) neurons, two populations targeted by sex steroids, in three diencephalic areas involved in the central control of ovulation and/or sexual behavior: the arcuate nucleus (ARC), the preoptic area (POA) and the ventrolateral part of the ventromedial hypothalamus (VMHvl). KP is the most potent secretagogue of GnRH secretion while SOM has been shown to centrally inhibit LH pulsatile release. Notably, hypothalamic contents of these two neuropeptides vary with photoperiod in specific seasonal species. Our hypothesis is that SOM inhibits KP neuron activity and therefore indirectly modulate GnRH release and that this effect may be seasonally regulated. We used sections from ovariectomized estradiol-replaced ewes killed after photoperiodic treatment mimicking breeding or anestrus season. We performed triple immunofluorescent labeling to simultaneously detect KP, SOM and synapsin, a marker for synaptic vesicles. Sections from the POA and from the mediobasal hypothalamus were examined using a confocal microscope. Randomly selected KP or SOM neurons were observed in the POA and ARC. SOM neurons were also observed in the VMHvl. In both the ARC and POA, nearly all KP neurons presented numerous SOM contacts. SOM neurons presented KP terminals more frequently in the ARC than in the POA and VMHvl. Quantitative analysis failed to demonstrate major seasonal variations of KP and SOM interactions. Our data suggest a possible inhibitory action of SOM on all KP neurons in both photoperiodic statuses. On the other hand, the physiological significance of KP modulation of SOM neuron activity and vice versa remain to be determined.

Somatostatinoma: a rare cause of diabetic ketosis

Somatostatinomas are rare gut neuroendocrine tumours. The classical ‘somatostatinoma syndrome’, secondary to the inhibitory action of somatostatin, comprises mild diabetes mellitus, gall bladder disease and diarrhoea with steatorrhoea. The diabetes is usually mild and not associated with major ketosis. We describe a 72 year-old man who presented with severe metabolic upset (hyperglycaemia, ketonuria and acute renal failure). He had lost significant amount of weight and was found to have extensive liver metastases. Biopsy confirmed a carcinoid tumour and somatostatin levels were markedly elevated in keeping with a diagnosis of metastatic somatostatinoma (probably of pancreatic origin). Paradoxically, a somatostatin analogue (octreotide, Sandostatin LAR) effectively controlled his symptoms and although insulin-dependent his daily requirement was never higher than 16 units. We speculate that his tumour secreted a spectrum of somatostatin-related peptides with a relatively greater inhibitory effect on the pancreatic secretion of insulin, compared to glucagon, and that this was responsible for the severe metabolic derangement at first presentation. Glycaemic status should always be assessed in patients with newly presenting carcinoid tumours.

Regulation of expression of the receptors controlling gastric acidity

Gastric acid secretion is regulated by the stimulatory effects of gastrin, histamine and acetylcholine and the inhibitory actions of somatostatin on their respective receptors. We proposed that the expression of these receptors could be regulated at the transcription level by agonists and antagonists known to effect acid secretion. A quantitative “real-time” PCR method was used to determine changes in mRNA expression for these receptors. The agonists, pentagastrin and histamine, and the H 2 antagonist, ranitidine, were infused over a 6 h period to conscious sheep. Blood, antral and fundic tissue samples were taken for analysis. Both pentagastrin and histamine resulted in elevated plasma somatostatin concentrations during the treatment. Ranitidine stimulated a fourfold increase in plasma gastrin while histamine caused a transient decrease. Except for an increase in antral gastrin following ranitidine infusion, there was no significant change in gastric gastrin and somatostatin concentration. Histamine (H 2) receptor mRNA expression in the antrum was significantly increased by pentagastrin and decreased by ranitidine. Pentagastrin also stimulated a significant increase in the level of muscarinic (M 3) receptor mRNA in the antrum. Antral somatostatin II receptor mRNA was significantly decreased by histamine. In the fundus, pentagastrin infusion resulted in a significant increase in histamine receptor mRNA and a decrease in the muscarinic receptor mRNA. This work demonstrates that the receptors involved in the regulation of acid secretion can be regulated by local events.

Regulation of carbachol-induced c-fos mRNA expression in AR42J cells by somatostatin receptor subtypes 1, 2, and 3.

Somatostatin is an inhibitory peptide that exerts its effects tissue-specifically by activating one or more of five receptors (SSTR 1-5). Although several studies have examined which SSTR subtypes control gastrointestinal function, effects of somatostatin on pancreatic gene expression are not well defined. To examine the effects of somatostatin and newly synthesized selective SSTR agonists on the cholinergically stimulated expression of the immediate early response gene In pancreatic acinar AR42J cells, polymerase chain reaction analysis revealed that mRNAs for SSTR 1, 2, and 3 were expressed. SSTR 4 and 5 were not detected. When AR42J cells were exposed to the cholinergic agonist carbachol in the presence of somatostatin or selective SSTR agonists, significant and dose-dependent reductions in agonist-induced levels of mRNA were noted. Pretreatment with agonists specific for SSTR 4 or 5 had no inhibitory effects. The inhibitory actions of somatostatin were pertussis toxin-sensitive. In addition, since somatostatin did not affect intracellular calcium homeostasis, the inhibitory actions of somatostatin are independent of calcium signaling. The current studies demonstrate that somatostatin inhibits carbachol-induced increases in expression by interacting with somatostatin receptor subtypes 1, 2, and 3. In addition, because somatostatin did not affect intracellular calcium homeostasis, it can be concluded that SSTR actions are independent of carbachol-stimulated calcium signaling.

Somatostatin inhibits exocytosis in rat pancreatic α‐cells by Gi2‐dependent activation of calcineurin and depriming of secretory granules

1. Measurements of cell capacitance were used to investigate the molecular mechanisms by which somatostatin inhibits Ca(2+)-induced exocytosis in single rat glucagon-secreting pancreatic alpha-cells. 2. Somatostatin decreased the exocytotic responses elicited by voltage-clamp depolarisations by 80 % in the presence of cyclic AMP-elevating agents such as isoprenaline and forskolin. Inhibition was time dependent and half-maximal within 22 s. 3. The inhibitory action of somatostatin was concentration dependent with an IC(50) of 68 nM and prevented by pretreatment of the cells with pertussis toxin. The latter effect was mimicked by intracellular dialysis with specific antibodies to G(i1/2) and by antisense oligonucleotides against G proteins of the subtype G(i2). 4. Somatostatin lacked inhibitory action when applied in the absence of forskolin or in the presence of the L-type Ca(2+) channel blocker nifedipine. The size of the omega-conotoxin-sensitive and forskolin-independent component of exocytosis was limited to 60 fF. By contrast, somatostatin abolished L-type Ca(2+) channel-dependent exocytosis in alpha-cells exposed to forskolin. The magnitude of the latter pool amounted to 230 fF. 5. The inhibitory effect of somatostatin on exocytosis was mediated by activation of the serine/threonine protein phosphatase calcineurin and was prevented by pretreatment with cyclosporin A and deltamethrin or intracellularly applied calcineurin autoinhibitory peptide. Experiments using the stable ATP analogue AMP-PCP indicate that somatostatin acts by depriming of granules. 6. We propose that somatostatin receptors associate with L-type Ca(2+) channels and couple to G(i2) proteins leading to a localised activation of calcineurin and depriming of secretory granules situated close to the L-type Ca(2+) channels.

Expression of receptors regulating gastric acidity in the developing sheep stomach

Acid secretion first appears in the stomach during the later stages of fetal development. Gastric acid secretion is regulated by the stimulatory effects of gastrin, histamine, acetylcholine and the inhibitory actions of somatostatin on their respective receptors. A semi-quantitative reverse transcriptase-polymerase chain reaction method for the determination of changes in mRNA expression for these receptors was developed and correlated with known changes in gastric acidity. Glyceraldehyde-3-phosphate dehydrogenase (GAP-DH) was used as a reference and an internal standard. The antrum and fundus from four age groups were assayed: 80 days of gestation, 110 days of gestation, term (145 days) and adult animals. The CCK B/gastrin and the histamine (H 2) receptor mRNA were significantly lower in samples from the fundus of fetuses, from 80 and 110 days of gestation when compared with the adult fundus. Histamine receptor mRNA in the antrum was also significantly lower in the 80 and 110 days of gestation samples relative to the term fetal antrum. Somatostatin II receptor mRNA levels in the antrum decreased with increasing age with no change in the fundus. These findings suggest that changes in receptor gene expression, may be responsible for the diminished gastric acidity and responsiveness observed in the fetal stomach.

Multiple mechanisms contribute to the inhibitory action of somatostatin on intestinal peristalsis in the mouse

Multiple mechanisms contribute to the inhibitory action of somatostatin on intestinal peristalsis in the mouse

Multiple mechanisms contribute to the inhibitory action of somatostatin on intestinal peristalsis in the mouse

Multiple mechanisms contribute to the inhibitory action of somatostatin on intestinal peristalsis in the mouse

Clinicopathological value of somatostatin type 2A and estrogen receptor immunoreactivity in human breast carcinoma.

Somatostatin type 2A (sstr2A) and estrogen receptor (ER) are interrelated regulatory receptors present in normal breast epithelium and in a population of breast carcinomas. ER mediates growth stimulatory effects of estrogens whereas sstr2A mediates growth inhibitory actions of somatostatin. However, much work has been devoted to elucidate the biological role of ER, little is known about sstr2A in breast cancer. In the present study we examined immunoreactivity of sstr2A and ER in 64 breast carcinomas in correlation with tumor size and histological grade (HG), presence of lymph node metastasis (LNM), Nottingham prognostic index (NPI), and the patients' age. ER and sstr2A immunoreactivity were present in 78% and 63% of the breast carcinomas, respectively. Ninety percent of tumors immunoreactive for sstr2A were simultaneously immunoreactive for ER. ER immunoreactivity correlated significantly with lower HG (p = 0.03) and better NPI (p = 0.02). sstr2A immunoreactivity correlated significantly with lower HG (p = 0.012) but not with NPI (p = 0.26). There was no correlation of sstr2A immunoreactivity and tumor size, patients' chronological age or LNM. The results confirm prognostic value of ER immunohistochemistry in breast carcinoma. However sstr2A cannot substitute ER for prognostic evaluation, sstr2A immunoreactivity being significantly associated with lower HG seems to represent an independent prognostic factor in breast carcinoma.

Somatostatin Inhibits Interleukin 6 Release from Rat Cortical Type I Astrocytes via the Inhibition of Adenylyl Cyclase

Interleukin 6 is a pleiotropic cytokine produced in the central nervous system (CNS) that has been involved in both direct neurotrophic activities and in the regulation of the production of acute phase proteins both at peripheral and central levels. In rat cortical type I astrocytes, interleukin 6 release is under the control of cAMP-protein kinase A and calcium-phospholipids-protein kinase C systems. Somatostatin is a neuropeptide, acting as a neurotransmitter, highly concentrated within the CNS, where it has been involved in the modulation of learning and memory processes. The aim of this study was to characterize the effects of somatostatin on the release of interleukin 6 from rat cortical type I astrocytes and the intracellular mechanisms involved in this activity. Our results show that somatostatin, in a concentration-dependent manner, inhibited basal and forskolin-stimulated interleukin 6 release from rat cortical type I astrocytes in culture. The EC50of the inhibitory action was calculated to be approximately 10 nM. Furthermore, this effect of somatostatin was completely abolished by pretreating cortical astrocytes with pertussis toxin that, uncoupling, by ADP-rybosylating, the inhibitory GTP-binding protein from the receptors, prevents the activation of the intracellular effectors such as the adenylyl cyclase enzyme. To identify the intracellular mechanism mediating the effects of somatostatin on the interleukin 6 release, we evaluated the peptide modulation of basal and stimulated intracellular accumulation of cAMP. In our experimental conditions somatostatin significantly inhibited both basal and forskolin-stimulated cAMP accumulation. Conversely, somatostatin did not affect the increase of interleukin 6 release induced by dibutyryl-cAMP, a nonhydrolizable cAMP analog that, bypassing the effects of somatostatin on adenylyl cyclase activity, directly activated protein kinase A. These observations support the hypothesis that somatostatin inhibitory activity on interleukin 6 release is mediated by its effects on cAMP production. Somatostatin analog SMS 201-995 did not affect interleukin 6 production either in basal or stimulated conditions. Since, SMS 201-995 was reported to bind with high affinity only to somatostatin receptors type 2, 3 and 5, the lack of effect of this compound on interleukin 6 release suggests that the inhibitory action of somatostatin could be mediated by the activation of either type 1 or type 4 somatostatin receptors. In conclusion, our data demonstrate that the release of interleukin 6 from rat cortical type I astrocytes is inhibited by somatostatin through the activation of a somatostatin receptor coupled to the inhibition of adenylyl cyclase via a G-protein sensitive to pertussis toxin.

ヒツジ下垂体前葉細胞における成長ホルモン放出ペプチド(GHRP-1)刺激時のGH放出と細胞内カルシウム濃度に及ぼすソマトスタチン,デキサメサゾンおよびオレイン酸の抑制効果

ヒツジ下垂体前葉細胞における成長ホルモン放出ペプチド(GHRP-1)刺激時のGH放出と細胞内カルシウム濃度に及ぼすソマトスタチン,デキサメサゾンおよびオレイン酸の抑制効果

Somatostatin inhibits AP-1 function via multiple protein phosphatases

We have reported previously that the widespread inhibitory actions of somatostatin might be mediated by its ability to inhibit the expression of the immediate early genes c-fos and c-jun. The products of these genes form a heterodimeric transcription factor complex [activator protein 1 (AP-1)], which is known to be induced by treatment with phorbol esters. In the present study, we sought to investigate the mechanisms by which somatostatin inhibits immediate early gene expression. For our experiments, we used a rat pituitary adenoma cell line (GH3), which is known to express multiple subclasses of somatostatin receptors. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulated both AP-1 binding and transcriptional activity in GH3 cells and the somatostatin analogue octreotide inhibited this response by 40-70%. In the presence of two different phosphatase inhibitors, sodium orthovanadate or okadaic acid, the ability of somatostatin to inhibit AP-1 binding and transcriptional activity was abolished. This effect of octreotide, which appears to be mediated by the SSTR2 and SSTR5 subtypes of somatostatin receptors, was paralleled by its ability to inhibit TPA-stimulated GH3 cell proliferation. Pretreatment of the GH3 cells with pertussis toxin (200 ng/ml) reversed the inhibitory effect of octreotide on both AP-1 function and cellular proliferation. Our observations lead us to conclude that somatostatin not only inhibits immediate early gene expression but also inhibits AP-1 binding and transcriptional activity via the action of several classes of protein phosphatases. This effect, which is pertussis toxin sensitive, might be one mechanism by which somatostatin inhibits cellular proliferation.

Somatostatin receptor subtype 3 mediates the inhibitory action of somatostatin on gastric smooth muscle cells.

Previous functional studies show that somatostatin (SS) interacts with specific receptors to inhibit relaxation in gastric smooth muscle cells. There are no ligand binding studies, and it is unknown which of the five subtypes of SS receptors mediates the action. Dispersed gastric smooth muscle cells from guinea pig bound both 125I-labeled SS-14 and 125I-D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Cys-Nal-NH2 (where Nal indicates N-naphthylalanine) (cyclo-SS-8), a synthetic peptidase-resistant octapeptide SS analogue. SS-28 and SS-14, cyclo-SS-8, and SS analogue D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol [SMS-(201-995) (octreotide)] inhibited 125I-cyclo-SS-8 binding with relative potencies of SS-28 = cyclo-SS-8 = SMS-(201-995) (octreotide), and the binding was not affected by the addition of protease inhibitors. SS-14 caused inhibition only in the presence of protease inhibitors. Ligand analysis demonstrated a two-binding-site model. Analysis of the relationship between biological function and binding suggested the high-affinity sites mediated the relaxant action of SS. 5'-Guanylylimidodiphosphate [Gpp-(NH)p] inhibited binding by reducing the affinity of the high-affinity site. Six SS-8 analogues that distinguish SS subtypes showed that 125I-SS-14 bound to somatostatin receptor subtype 3 (SSTR3). The results demonstrated that gastric smooth muscle cells possess distinct receptors for SS of the SSTR3 subtype. Occupation of these sites inhibits relaxation in gastric smooth muscle cells. Modulation between the high- and low- affinity binding states of SSTR3 is at least partially mediated by activation of guanine nucleotide regulatory proteins.

Molecular basis for somatostatin action: inhibition of c-fos expression and AP-1 binding

The mechanisms by which somatostatin exerts its widespread inhibitory actions have been investigated extensively but understood only partially. Recent studies have shown that somatostatin can inhibit gene transcription directly. In view of the critical importance of early response genes in induction of gene expression, we examined whether the action of somatostatin might be mediated by inhibition of early response genes. The products of some of these genes, such as c-fos and c-jun, are known to form a heterodimeric transcription factor complex (AP-1) that binds specifically to the consensus sequence TGAC(G)TCA. Accordingly, we examined the effects of somatostatin on c-fos gene expression and on the binding of the AP-1 complex to its specific DNA element using isolated gastric parietal cells and the GH3 pituitary cell line. In both parietal and GH3 cells, c-fos-specific mRNA was increased by agents known to act via both adenosine-3',5'-cyclic monophosphate and Ca(2+)-dependent signaling mechanisms, and octreotide significantly inhibited this response. Pertussis toxin pretreatment (200 ng/ml) reversed the inhibitory effect of octreotide. AP-1 binding activity, assessed by gel shift assays using a 32P-labeled AP-1 oligonucleotide probe, was stimulated by dibutyryl adenosine 3',5'-cyclic monophosphate and serum and inhibited by octreotide treatment. Our observations support the notion that the universal inhibitory action of somatostatin may be mediated by inhibition of expression of early response genes via a pertussis toxin-sensitive inhibitory pathway. This effect appears to lead to decreased binding of regulatory nuclear proteins to their specific DNA elements resulting, presumably, in diminished gene expression.

Somatostatin inhibits CCK release by inhibiting secretion and action of CCK-releasing peptide.

We hypothesized that somatostatin exerts its inhibitory action on cholecystokinin (CCK) release and pancreatic secretion by inhibiting the secretion and/or action of a CCK-releasing peptide (CCK-RP) secreted from the small intestine. Our studies demonstrated that intravenous infusion of somatostatin (25 micrograms.kg-1.h-1) completely inhibited the increase in amylase output evoked by diversion of bile-pancreatic juice and 80 +/- 10% of the increase in plasma CCK. Intraduodenal administration of concentrated intestinal perfusate containing the CCK-RP collected from a donor rat with bile-pancreatic juice diversion raised amylase output by 2.3-fold and elevated plasma CCK levels to 7 +/- 0.8 pM in a recipient rat. The stimulatory effect of the concentrated intestinal washings was abolished when the "donor" rat was pretreated with somatostatin. In addition, in somatostatin-treated "recipient" rats, intraduodenal administration of intestinal washings containing CCK-RP also failed to elicit an increase in plasma CCK and amylase secretion. Furthermore, using duodenal mucosal explants, we demonstrated that the inhibitory action of somatostatin on CCK release evoked by CCK-RP was antagonized by pretreatment with pertussis toxin. These observations strongly suggest that somatostatin inhibits feedback regulation of pancreatic enzyme secretion by inhibiting both the secretion and action of CCK-RP.

Inhibitory action of somatostatin on cAMP dependent pepsinogen secretion from rat gastric chief cells: involvement of pertussis toxin-sensitive G-protein.

We examined the inhibitory effect of somatostatin on pepsinogen secretion using isolated rat gastric chief cells. Secretin and forskolin significantly increased not only pepsinogen secretion from chief cells but also cellular cAMP accumulation in a dose-dependent fashion. Somatostatin significantly inhibited secretin- and forskolin-induced pepsinogen secretion and secretin-induced cellular cAMP accumulation. However, forskolin-induced cellular cAMP accumulation was not inhibited by somatostatin. The inhibitory effect of somatostatin on secretin-induced pepsinogen secretion was abolished by pretreatment with pertussis toxin, but inhibition of forskolin-, carbachol- and cholecystokinin octapeptide-induced pepsinogen secretion was not. These results suggest that somatostatin inhibits pepsinogen secretion in two ways, one is closely related to the pertussis toxin-sensitive G-protein and the other is not determined.

Somatostatin inhibits gastrin-induced histamine secretion and synthesis in the rat

Somatostatin is a potent inhibitor of gastric acid secretion. However, the effect of somatostatin on gastric histamine secretion and synthesis has not been well understood, despite the fact that histamine plays a key role in the regulation of gastric acid secretion. This study was designed to determine the effect of somatostatin on gastric histamine mobilization and acid secretion in conscious rats. In conscious rats with a gastric fistula, a 4 h intravenous infusion of gastrin-17 I (1 nmol/kg/h) evoked a marked increase in fundic histidine decarboxylase activity (the sole histamine-forming enzyme) and reduced fundic histamine content with a concomitant increase in gastric acid secretion. Somatostatin-14 (10 nmol/kg/h) significantly inhibited gastrin-induced gastric acid secretion and fundic histidine decarboxylase activity and prevented a gastrin-induced decrease in fundic histamine content. In conscious rats with a vesical fistula, somatostatin-14 (10 nmol/kg/h) significantly inhibited the urinary histamine excretion induced by a gastrin-17 I (1 nmol/kg/h) infusion. These findings suggest that the inhibitory action of somatostatin on gastrin-induced acid secretion is mediated by the inhibition of histamine mobilization.

Mechanisms of action of long-acting analogs of somatostatin

The prolactin secreting rat pituitary tumor cell line, GH 3, expresses high affinity receptors for both vasoactive intestinal peptide (VIP) and somatostatin (SS 14). VIP induces prolactin secretion by GH 3 cells, an action which is antagonized by SS 14. This in vitro model was used to examine the mechanism of action of two synthetic somatostatin analogs, d-Phe-Cys-Phe- d-Trp-Lys-Thr-Cys-Thr-OH (octreotide; SMS 201–995) and cyclo(aminoheptanoyl-Phe- d-Trp-Lys-Thr (benzyl)) (cyclic pentapeptide; CPP). Octreotide and CPP bind to the pituitary somatostatin receptor with lower affinity than does SS 14 ( K D = 1.3 ± 1.1 ; 80 ± 29; 211 ± 107 nM for SS 14, octreotide and CPP, respectively). SS 14 and octreotide were equally effective as inhibitors of VIP-mediated accumulation of cAMP (40% and 45% inhibition, respectively, P < 0.01). SS 14 and octreotide also inhibited forskolin-mediated accumulation of cAMP (42% and 40% inhibition of cAMP production, respectively; P < 0.01). The inhibitory action of somatostatin and octreotide on both VIP- and forskolin-mediated cAMP accumulation was blocked by pre-treatment of GH 3 cells with pertussis toxin ( P < 0.001). Neither SS 14 nor octreotide affects the apparent affinity of VIP for its specific receptors on GH 3 cells; thus, the inhibitory action of SS 14 and octreotide appears to be mediated at the locus of the G-protein-adenylate cyclase complex. In contrast, CPP inhibited VIP-mediated cAMP accumulation slightly, but had no effect on forskolin-mediated cAMP production. Pertussis toxin did not attenuate CPP affects on VIP-mediated cAMP accumulation. However, pre-incubation of GH 3 cells with CPP decreased the apparent affinity of receptors for VIP, suggesting that effects of CPP are attributable to interference with VIP binding rather than inhibition at the G-protein-adenylate cyclase complex.

Spontaneous pulsatile growth hormone release in male and female premature infants.

Although premature infants have high umbilical cord GH levels, little is known about spontaneous GH release in these individuals. The purpose of our study was to investigate spontaneous 12-h GH release in appropriate for gestational age male and female premature infants. We studied 22 premature infants (15 males and 7 females) of appropriate length and weight for age. Gestational ages, birth weights, birth lengths, and ages at the time of study were similar in male or female infants. All infants were biochemically euthyroid. Blood was taken every 30 min over a 12-h period from an indwelling umbilical catheter; no stress occurred during the blood withdrawal. GH was determined by a double antibody RIA, using 0.01 mL plasma. GH pulse detection was undertaken using Cluster, a computerized pulse detection algorithm. Total insulin-like growth factor-I and -II (IGF-I and -II) levels were measured after separation of the IGFs from the serum binding proteins. Spontaneous pulsatile GH release was observed in all infants studied. No differences were found between males and females in the pulse characteristics of frequency, maximal amplitude, incremental amplitude, width, or area. The GH pulse frequency per 12 h was 3.2 +/- 0.3 (mean +/- SE) in males and 3.0 +/- 0.7 in females. The maximal pulse amplitude was 50.7 +/- 6.2 micrograms/L in males and 44.7 +/- 9.0 micrograms/L in females. The incremental pulse amplitude was 24.3 +/- 3.2 micrograms/L in males and 20.2 +/- 3.9 micrograms/L in females. The mean 12-h GH level was 37.1 +/- 4.8 micrograms/L in males and 35.8 +/- 8.5 micrograms/L in females; the average GH nadir was 26.1 +/- 4.0 micrograms/L in males and 24.4 +/- 8.3 micrograms/L in females. Both IGF-I and IGF-II concentrations were similar in males and females. The mean IGF-I levels were 10.7 +/- 1.5 ng/mL in males and 7.5 +/- 1.1 ng/mL in females; IGF-II levels were 96.0 +/- 12.0 ng/mL in males and 115.4 +/- 17.1 ng/mL in females. These results demonstrate similar pulsatile GH release in male and female premature infants at a mean age of 32-33 weeks. Compared with previously reported values for mean GH concentration and average GH nadir in older children, the values in these premature infants were much higher. We speculate that the higher GH levels in premature infants may result from decreased negative feedback associated with low IGF-I levels. The premature infant's somatotrophs may also not fully respond to the GH inhibitory action of somatostatin.

Aging enhances inhibitory action of somatostatin in rat pancreas.

This study examines the effects of donor age on exogenous somatostatin inhibition of insulin secretion stimulated by 10 mM D-glyceraldehyde and by 20 mM beta-D-glucose in isolated perfused rat pancreas. Both 6 and 30 nM synthetic somatostatin-14 affect both glyceraldehyde- and glucose-stimulated insulin secretion to a greater degree in pancreases from old animals (24-27 months) than in those from young (2-5 months). We conclude that an increased sensitivity to inhibitory actions of somatostatin during aging, observed in pituitary tissues in vitro, occurs in pancreatic tissues as well and may constitute a general phenomenon in tissues subject to somatostatin inhibition.