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PubMed2001

Specific secretion of gel-forming mucins and TFF peptides in HT-29 cells of mucin-secreting phenotype.

Trefoil factor family (TFF) peptides are typical secretory products of mucin-producing cells, e.g. of the gastrointestinal tract. Here, the expression and secretion of mucins and TFF peptides was studied in the HT-29 cell line throughout cellular growth and differentiation in relation to a mucin-secreting (HT-29 MTX) or an enterocyte-like (HT-29 G(-)) phenotype. mRNAs of several MUC and TFF genes were expressed in both cell subpopulations. However, for most MUC and TFF genes, the expression appeared strongly induced with the differentiation into the mucin-secreting phenotype. On the other hand, TFF2 was specifically expressed in the mucin-secreting HT-29 MTX cells. The differentiation of HT-29 MTX cells into the mucin-secreting phenotype was characterised by secretion of the gel-forming mucins MUC2, MUC5AC, and MUC5B, however, according to a different pattern in the course of differentiation. A significant amount of TFF1 and TFF3 was secreted after differentiation, also according to a different pattern, whereas TFF2 was only faintly detected. Secretagogues, known to induce the secretion of mucus, increased the secretion of all three TFF peptides. In contrast, neither a secretory mucin nor a TFF peptide was found in the culture medium of HT-29 G(-) cells. Overlay assays indicated that HT-29 MTX mucins bound to secretory peptides of HT-29 MTX cells with relative molecular mass similar to TFF peptides. TFF1 and TFF3 were specifically localised in the mucus layer of HT-29 MTX cells by confocal microscopy. Finally, the secretion of TFF peptides and mucins appears as a co-ordinated process which only occurs after differentiation into goblet cell-like phenotype.

Cell Differentiation↗
PubMed1999

T lymphocytes downregulate granulocyte-macrophage colony-stimulating factor secretion from stimulated monocytes by increasing the secretion of monocyte-derived interleukin-10.

In previous studies we characterized the cytokine regulation of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) secretion by endothelial cells and monocytes and found differences in secretion pattern within and between these cell systems. In this study, the regulatory effect of T lymphocytes on CSF secretion was examined. T lymphocytes had no effect on CSF secretion by endothelial cells. In contrast, the addition of T lymphocytes significantly and dose dependently downregulated GM-CSF, but not G-CSF, secretion by monocytes. In one of our previous studies it was shown that interleukin-4 (IL-4) and interleukin-10 (IL-10) were the most potent inhibitory cytokines of CSF secretion by monocytes. Both these cytokines are produced by T lymphocytes. However, the downregulating effect on monocyte GM-CSF secretion was not due to increased secretion of T-lymphocyte-derived IL-4 or IL-10. Instead, the presence of T lymphocytes increased the secretion of monocyte-derived IL-10. It was shown earlier than IL-10 regulates CSF secretion by monocytes in an autocrine manner. Our data indicate that T lymphocytes might interfere with this autocrine regulation and thereby influence monocyte function in immune response and cell proliferation.

Cells, Cultured↗
PubMed1995

Effects of hydration state on the synthesis and secretion of triacylglycerol by isolated rat hepatocytes. Implications for the actions of insulin and glucagon on hepatic secretion.

The effects of hepatocyte volume on the secretion of triacylglycerol were studied in order to test the suggestion that increases in the portal concentrations of osmolyte amino acids and metal ions during the prandial/early-absorptive phase may be involved in mediating the acute changes in glycerolipid metabolism observed in vivo [Zammit (1995) Biochem Soc. Trans. 23, 506-511]. Incubation of isolated rat hepatocytes with hypo-osmotic medium or in the presence of glutamine (in the presence or absence of leucine), conditions which gave an increase in cell water content of between 8 and 27%, resulted in a decrease in the rate of [14C]triacylglycerol (TAG) secretion when [14C]palmitate was used as substrate. The inhibition was proportional to the increase in cell water content. At low exogenous palmitate concentration (0.05 mM), the inhibition of [14C]TAG secretion was accompanied by a marked shift in the incorporation of label from TAG to phospholipid. In the presence of 0.5 mM palmitate this effect was attenuated, and in the presence of 1 mM palmitate it was abolished. Increased cell volume associated with incubation of hepatocytes with glutamine (in the presence or absence of leucine) also resulted in a decrease in the fraction of newly labelled TAG that was secreted into the medium. Decreased cell volume, achieved by incubation of hepatocytes with hyperosmotic medium (sufficient to decrease cell water content by approx. 9%) decreased overall [14C]TAG secretion, but did not affect the amount of label that was incorporated into phospholipid as a fraction of that incorporated into total glycerolipids. Cell shrinkage, however, diminished the fraction of newly labelled [14C]TAG that was secreted. When intracellular TAG was prelabelled with [3H]glycerol, it was found that cell shrinkage markedly inhibited (preformed) [3H]TAG secretion, whereas cell swelling did not affect this route of TAG secretion. The data are discussed in terms of the possible action of changes in cell hydration at the different loci at which hepatocyte TAG secretion is controlled, with reference to previous observations that both insulin and glucagon are able to inhibit TAG secretion in cultured rat hepatocytes and HepG2 cells.

Amino Acids↗
PubMed2000

The virulence plasmid pWR100 and the repertoire of proteins secreted by the type III secretion apparatus of Shigella flexneri.

Bacteria of Shigella spp. are the causative agents of shigellosis. The virulence traits of these pathogens include their ability to enter into epithelial cells and induce apoptosis in macrophages. Expression of these functions requires the Mxi-Spa type III secretion apparatus and the secreted IpaA-D proteins, all of which are encoded by a virulence plasmid. In wild-type strains, the activity of the secretion apparatus is tightly regulated and induced upon contact of bacteria with epithelial cells. To investigate the repertoire of proteins secreted by Shigella flexneri in conditions of active secretion, we determined the N-terminal sequence of 14 proteins that are secreted by a mutant in which secretion was deregulated. Sequencing of the virulence plasmid pWR100 of the S. flexneri strain M90T (serotype 5) has allowed us to identify the genes encoding these secreted proteins and suggests that approximately 25 proteins are secreted by the type III secretion apparatus. Analysis of the G+C content and the relative positions of genes and open reading frames carried by the plasmid, together with information concerning the localization and function of encoded proteins, suggests that pWR100 contains blocks of genes of various origins, some of which were initially carried by four different plasmids.

Amino Acid Sequence↗
PubMed2000

Evidence for the secretion of Chlamydia trachomatis CopN by a type III secretion mechanism.

The medically significant, obligate intracellular pathogen Chlamydia trachomatis replicates within vacuoles termed inclusions. A developmental cycle is initiated after entry into a host cell and is manifested by the transformation of infectious elementary bodies (EBs) to larger, non-infectious reticulate bodies (RBs). Analysis of the C. trachomatis genome has revealed that chlamydiae possess genes that may encode a type III secretion apparatus. In other Gram-negative pathogens, the type III secretion mechanism is used to target virulence factors directly to the host cell cytoplasm and is essential for full virulence. To evaluate the possibility of a functional type III secretion mechanism in C. trachomatis, we initially focused on a locus containing genes encoding products with similarity to chaperones (Scc1), secretion pore components (Cds1 and Cds2) and secreted proteins (CopN) from other type III systems. Gene expression was tested by reverse transcriptase-polymerase chain reaction (RT-PCR) of total RNA extracted from infected HeLa cell monolayers at 2, 6, 12 and 20 h after infection and normalized for the number of C. trachomatis genomes present. Message was detected for Scc1 at all times, whereas message for all other tested genes was detected in significant amounts at 12 h and 20 h. Immunoblot analysis with Scc1- and CopN-specific antibodies revealed that CopN and Scc1 were present in EBs, RBs and whole-culture extracts harvested 20 h after infection. CopN is homologous to the secreted protein YopN of Yersinia sp., and analysis of monolayers 20 h after infection via indirect immunofluorescence showed specific labelling of inclusion membranes when probed with CopN-specific antibodies but not with Scc1-specific antibodies. His-tagged CopN and a chlamydial cytoplasmic control protein (NrdB) were expressed in Yersinia enterocolitica containing or lacking the virulence plasmid pYV. CopN, but not NrdB, was secreted by Y. enterocolitica in a Ca2+- and pYV-dependent fashion. These data indicate that components of the putative type III apparatus of C. trachomatis are expressed and that at least one of these products is secreted by chlamydiae to the inclusion membrane. The observation that CopN is also secreted by the Yersinia type III apparatus provides support for the notion that chlamydiae secrete proteins via a type III mechanism.

Bacterial Proteins↗
PubMed2005

A secreted regulatory protein couples transcription to the secretory activity of the Pseudomonas aeruginosa type III secretion system.

The type III secretion system (T3SS) of Pseudomonas aeruginosa is an important virulence determinant. Transcription of the T3SS is highly regulated and intimately coupled to the activity of the type III secretion channel. The secretion channel is generally closed, and transcription is repressed. Inducing signals such as calcium depletion, however, open the secretion channel and derepress transcription of the T3SS. The coupling of transcription with secretion requires three previously identified cytoplasmic regulatory proteins. ExsA is a DNA-binding protein required for transcriptional activation of the entire T3SS. The second regulatory protein, ExsD, functions as anti-activator by directly binding to ExsA. Finally, ExsC functions as an anti-anti-activator by directly binding to and inhibiting ExsD. Although the regulatory roles of ExsC, ExsD, and ExsA were defined through these previous studies, the mechanism of coupling transcription to secretion was unclear. We now report the identification of ExsE as a secreted regulator of the T3SS and provide evidence that ExsE functions as a direct inhibitor of ExsC. When the secretion channel is closed, ExsE is complexed with ExsC in the cytoplasm, and transcription of the T3SS is repressed by sequestration of ExsA by ExsD. We propose that the secretion of ExsE provides an initiating signal that results in an equilibrium shift whereby ExsC becomes preferentially bound to ExsD, thus allowing liberated ExsA to activate transcription of the T3SS. The presence of ExsE homologs in the T3SSs of other bacterial species suggests that this mechanism of coupling transcription to secretion may be commonly used.

Bacterial Proteins↗
PubMed1999

Immunoglobulin-secreting cells in the surface secretion on the pharyngeal tonsils.

As B-lymphocytes on the pharyngeal tonsils constitute a considerable part of the leukocytes in the surface secretion, and their biological role is obscure, we explored their possible function with respect to immunoglobulin production. Twenty children scheduled for routine adenoidectomy participated. Surface secretion from 10 children was analysed for presence of plasma cells and cells from the secretions of the other 10 children were tested in enzyme-linked immunosorbent spot assays (ELISPOT-assays) for their capacity to secrete and produce IgA, IgM and IgG. Plasma cells and cells that secreted IgA, IgM and IgG respectively were present in the secretions of all tested children. In eight of ten children the IgG immunocytes, Ig-producing blasts and plasma cells. outnumbered the IgA immunocytes. The number of immunoglobulin secreting cells (ISCs) was reduced by half or more in cell suspensions exposed to the reversible protein synthesis inhibitor cycloheximide. It is concluded that immunocytes that produce and secrete immunoglobulin are present in the surface secretion on the pharyngeal tonsils. The production represents an addition to the immunoglobulins transported to the secretion by the poly-Ig receptor and by passive diffusion. The results shed new light on the pathogenesis of mucosal infections in the upper airways.

Adenoids↗
PubMed2000

Intravenous bilirubin, dibromosulfophthalein, and bromosulfophthalein infusions uncouple biliary phospholipid and cholesterol secretion from bile acid secretion by inhibiting hepatic phosphoglycoprotein-3 activity in pigs.

BACKGROUND: Biliary secretion of organic anions disturbs the proportional relationship normally pertaining between biliary lipid and bile acid secretion. The mechanism causing this uncoupling of biliary lipid from bile acid secretion is incompletely understood. Impaired micellization of membrane lipids by bile due to biliary contamination with organic anions or lowering of biliary bile acid concentration by enhanced bile acid-independent bile flow has been proposed as causative factors. Recently, we found that hepatic phosphoglycoprotein 3 (pgp3) activity was reduced in pigs during bilirubin-induced uncoupling of biliary lipid from bile acid secretion. Pgp3 is the phosphatidylcholine flippase in the canalicular membrane sustaining biliary phospholipid secretion in pigs. This investigation was undertaken to examine whether bilirubin, dibromosulfophthalein, and bromosulfophthalein uncouple biliary lipid from bile acid secretion by the same mechanism. METHODS/RESULTS: Hepatic bile was collected from 24 anesthetized pigs before and during infusion of 0.63 micromol x kg body wt(-1) x min(-1) intravenous bilirubin, dibromosulfophthalein, or bromosulfophthalein. Bile acid secretion was varied by intraportal cholic acid infusion. Hepatic pgp3 expression was measured by means of Western blot, using C219 antibody. Bilirubin > dibromosulfophthalein > bromosulfophthalein lowered biliary lipid secretion without altering hepatic pgp3 expression, increased bile acid-independent bile flow (bromosulfophthalein > dibromosulfophthalein > bilirubin), and enhanced the capacity of bile to micellize membrane lipids as assayed by means of erythrocyte lysis. Biliary bile acid concentration did not determine biliary lipid secretion. CONCLUSION: Bilirubin, dibromosulfophthalein, and bromosulfophthalein in bile uncouple biliary lipid from bile acid secretion by inhibiting hepatic pgp3 phosphatidylcholine flippase activity, putatively through diffusing into the pgp3 pore.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2006

Extracellular secretion of Escherichia coli alkaline phosphatase with a C-terminal tag by type I secretion system: purification and biochemical characterization.

Type I secretion system (TISS) of Gram-negative bacteria permits proteins to be secreted directly from the cytoplasm to the external medium by a single, energy-coupled step. To examine whether this system can be used as an extracellular production system of recombinant proteins, Escherichia coli alkaline phosphatase (AP) was fused to a C-terminal region of Pseudomonas sp. MIS38 lipase (PML) and examined for secretion using the E.coli cells carrying the heterologous TISS. PML is one of the passenger proteins of TISS and contains 12 repetitive sequences and a secretion signal at the C-terminal region. The fusion protein was efficiently secreted to the extracellular medium, while AP was not secreted at all, indicating that the secretion of AP is promoted by a secretion signal of PML. The repetitive sequences were not so important for secretion of the fusion protein, because the secretion level of the fusion protein containing entire repeats ( approximately 10 mg/l culture) was only 2-fold higher than that of the fusion protein without repeats. The fusion protein purified from the culture supernatant existed as a homodimer, like AP, and was indistinguishable from AP in enzymatic properties and stability.

Alkaline Phosphatase↗
PubMed1996

Analysis of the C-terminal secretion signal of the Rhizobium leguminosarum nodulation protein NodO; a potential system for the secretion of heterologous proteins during nodule invasion.

We used deletions to analyze the domains required for secretion of the Rhizobium leguminosarum bv. viciae nodulation protein, NodO, by the sec-independent pathway. Deletion of the C-terminal 24 amino-acids (residues 261 to 284) reduced secretion by at least 95%. A monoclonal antibody that recognizes the C-terminal domain of NodO was used to identify four nested deletions that retained the C-terminal 24 residues of NodO but had lost up to 133 residues (amino acids 128 to 259); all four proteins were secreted into the growth medium with an efficiency between 50 and 90% of normal. A deleted derivative of NodO that retained residues 1 to 21 and 167 to 284 (and therefore lacked most of the N-terminal Ca(2+)-binding domain) was secreted at around 80% of normal efficiency. Taken together, these observations indicate that the C-terminal 24 amino acids are sufficient for NodO secretion although the region adjacent to this domain appears to affect secretion efficiency. A derivative of the Escherichia coli alkaline phosphatase (phoA) gene was cloned into two derivatives of nodO such that PhoA (lacking the N-terminal transit peptide) was in-frame at both ends, with the C terminus fused to either the last 24 or 50 amino acids of NodO. These fusion proteins were secreted at 40 and 80% of the wild-type level, respectively, and the larger of the two retained alkaline phosphatase activity. A hybrid protein, containing E. coli beta-glucuronidase (GUS) fused to the N terminus of NodO, was not secreted, and it reduced the levels of wild-type NodO secreted by R. leguminosarum bv. viciae. The nature of the NodO C-terminal secretion signal is discussed with regard to its use as a delivery system for heterologous proteins useful for investigating the Rhizobium-legume interaction.

Amino Acid Sequence↗
PubMed1994

The Pseudomonas fluorescens lipase has a C-terminal secretion signal and is secreted by a three-component bacterial ABC-exporter system.

Both Pseudomonas aeruginosa and Pseudomonas fluorescens secrete a lipase into the extracellular medium. Unlike the lipase of P. aeruginosa, the lipase produced by P. fluorescens does not contain any N-terminal signal sequence. We show that the P. fluorescens lipase is secreted through the signal peptide-independent pathway of the alkaline protease that we previously identified in P. aeruginosa. Secretion of this protease (AprA) is dependent on the presence of three genes located adjacent to the aprA gene, aprD, aprE and aprF. The three secretion functions permit an efficient secretion of P. fluorescens lipase. Inactivation of one of them (AprE) prevented this secretion. In Escherichia coli, the three proteins AprD, AprE, AprF are necessary and sufficient for efficient secretion of lipase to the extracellular medium. The secretion signal is located within the C-terminal part of the lipase sequence and can promote efficient secretion of a passenger protein. Thus the P. fluorescens lipase secretion system belongs to the group of the three-component bacterial ABC-exporter systems.

ATP-Binding Cassette Transporters↗
PubMed2005

Activities of Pseudomonas aeruginosa effectors secreted by the Type III secretion system in vitro and during infection.

Pseudomonas aeruginosa utilizes a number of distinct pathways to secrete proteins that play various roles during infection. These include the type II secretion system, which is responsible for the secretion of the majority of exoproducts into the surrounding environment, including toxins and degradative enzymes. In contrast, the type III secretion system mediates the delivery of protein effectors directly into the cytoplasm of the host cell. Using tissue culture assays and a mouse acute-pneumonia model, we have determined the contribution of each of the type III effectors during infection. In strain PAK, ExoS is the major cytotoxin required for colonization and dissemination during infection. ExoT confers protection of tissue culture cells from type III-dependent lysis, while ExoY seemed to have little effect on cytotoxicity. ExoU is over 100-fold more cytotoxic than ExoS. The cytotoxicity of type II secretion was determined following deletion of the genes for the more toxic type III secretion system. The participation of these secretion systems during lifelong colonization of cystic fibrosis (CF) patients is unclear. By comparing clonal strains from the same patient isolated at the initial onset of P. aeruginosa infection and more than a decade later, after chronic colonization has been established, we show that initial strains are more cytotoxic than chronic strains that have evolved to reduce type III secretion. Constitutive expression of genes for the type III secretion system restored ExoS secretion but did not always reestablish cytotoxicity, suggesting that CF strains accumulate a number of mutations to reduce bacterial toxicity to the host.

ADP Ribose Transferases↗
PubMed1999

The Avr (effector) proteins HrmA (HopPsyA) and AvrPto are secreted in culture from Pseudomonas syringae pathovars via the Hrp (type III) protein secretion system in a temperature- and pH-sensitive manner.

We present here data showing that the Avr proteins HrmA and AvrPto are secreted in culture via the native Hrp pathways from Pseudomonas syringae pathovars that produce these proteins. Moreover, their secretion is strongly affected by the temperature and pH of the culture medium. Both HrmA and AvrPto were secreted at their highest amounts when the temperature was between 18 and 22 degrees C and when the culture medium was pH 6.0. In contrast, temperature did not affect the secretion of HrpZ. pH did affect HrpZ secretion, but not as strongly as it affected the secretion of HrmA. This finding suggests that there are at least two classes of proteins that travel the P. syringae pathway: putative secretion system accessory proteins, such as HrpZ, which are readily secreted in culture; and effector proteins, such as HrmA and AvrPto, which apparently are delivered inside plant cells and are detected in lower amounts in culture supernatants under the appropriate conditions. Because HrmA was shown to be a Hrp-secreted protein, we have changed the name of hrmA to hopPsyA to reflect that it encodes a Hrp outer protein from P. syringae pv. syringae. The functional P. syringae Hrp cluster encoded by cosmid pHIR11 conferred upon P. fluorescens but not Escherichia coli the ability to secrete HopPsyA in culture. The use of these optimized conditions should facilitate the identification of additional proteins traveling the Hrp pathway and the signals that regulate this protein traffic.

Bacterial Outer Membrane Proteins↗
PubMed1982

Physiological conditions for the study of basal and meal stimulated exocrine pancreatic secretion in the dog. Absence of feedback inhibition of basal secretion.

Pancreatic secretion has been studied in dogs in basal and postprandial conditions, as nearly physiological as possible. When pancreatic juice was excluded from the duodenum pancreatic secretion was not raised, compared with secretion during the return of juice to the duodenum. In fact, in seven mongrels, returning pancreatic juice led a transient rise in pancreatic secretion. This was not seen in five beagles. These results indicate that dogs do not manifest the feedback control of pancreatic secretion by pancreatic juice observed in other species. Pancreatic secretory activity was determined in 10 dogs after stimulation by food. The highest secretion rates occurred during the initial 60 min. The maximal secretion of protein occurred before the maximal secretion of fluid and bicarbonate. The effect of the meal diminished slowly during the subsequent minutes but did not reach basal levels after 2 h. In physiological conditions, maximal pancreatic secretion of fluid and bicarbonate was about one-fifth and of protein was almost one-seventh of the maximal secretory capacity obtained with secretin and cholecystokinin, respectively. Potential specific activity of trypsinogen was unchanged during the different experimental conditions. Trypsinogen output represented a constant average of 20% of protein output. The interindividual variability of pancreatic secretion rates was reduced when outputs were expressed per kilogram of body weight. In general, a significant positive correlation was found between body weight and the secretory outputs. No differences were observed in the response of mongrel and beagle dogs to a meal.

Animals↗
PubMed1991

Gastric HCO3- secretion: relationship with Na+ secretion and effect of acetazolamide in humans.

We examined the relationship between gastric HCO3- and Na+ secretion under fasting and sham-fed conditions in nine healthy men and also evaluated the effect of the carbonic anhydrase inhibitor acetazolamide on gastric secretion of HCO3- and Na+. Secretion of H+, K+, and Cl- were also measured. Gastric HCO3- secretion rates under fasting and sham-fed conditions closely paralleled Na+ secretion rates. A maximally tolerated intravenous dose (10 mg/kg) of acetazolamide significantly inhibited H+, Cl- and K+ secretion but did not significantly affect Na+ or HCO3- secretion. Thus the gastric mucosa secretes HCO3- and Na+ in parallel in humans both under fasting and sham-fed conditions. Relative to parietal secretion of HCl, nonparietal secretion of HCO3- and Na+ is resistant to carbonic anhydrase inhibition.

Acetazolamide↗
PubMed2006

Vasoactive intestinal peptide stimulates mucus secretion, but nitric oxide has no effect on mucus secretion in the ferret trachea.

Vasoactive intestinal peptide (VIP) and nitric oxide (NO) are neurotransmitters involved in the regulation of bronchial and pulmonary vascular tone. Published studies of the effects of VIP on airway mucus secretion have yielded conflicting results. The purpose of this study was to determine the effect of VIP on mucus secretion in the ferret trachea and if this effect was influenced by NO. We used a sandwich enzyme-linked lectin assay to measure mucin secretion and a turbidimetric assay to measure lysozyme (serous cell) secretion from ferret tracheal segments. VIP (10(-7) M) increased mucin secretion over 2 h. VIP (10(-9) to 10(-5) M) stimulated mucin secretion in a dose-dependent fashion. VIP-induced mucin secretion was partially blocked by a VIP receptor antagonist (a chimeric VIP-pituitary adenylate cyclase-activating peptide analog, VIP receptor antagonist) at a 10-fold excess concentration. At all concentrations tested, neither NG-nitro-L-arginine methyl ester, an inhibitor of NO synthase, nor S-nitroso-N-acetyl-penicillamine, an NO donor, had any significant effect on constitutive or VIP-induced mucus secretion. We conclude that VIP-stimulated mucin and lysozyme secretion was both time dependent and dose dependent and that NO neither stimulates nor inhibits mucus secretion in the ferret trachea.

Animals↗
PubMed1988

Growth hormone secretion during sleep. I. Comparison with GH responses to conventional pharmacologic stimuli in pubertal and early pubertal short subjects. Effects of treatment with human GH in patients with discrepant measurements of GH secretion.

Growth hormone (GH) was measured in 215 short children (147 males and 68 females, 123 prepubertal, 92 at early pubertal stages), comparing GH responses to classical pharmacologic stimulation tests and spontaneous GH secretion during sleep. GH secretion during sleep, but not GH responses to stimuli, was higher in early pubertal than in prepubertal subjects. The patients were classified into five groups, according to the agreement between GH responses to stimuli and GH secretion during sleep: group I, normal GH-secreting children; group II, completely GH-deficient; group III, partially GH-deficient; group IV, with normal secretion during sleep and low responses to stimuli; group V, with the reverse situation. 30% of the patients were in groups IV and V, both at prepubertal and early pubertal stages. 46 patients of groups II-V were treated with extracted human GH(hGH). The growth rate was enhanced in groups IV and V, to the same extent as in groups II and III. Four points can be concluded: (1) the rise of GH secretion during sleep is an early event at the onset of puberty; (2) the discrepancy between the GH responses to classical stimuli and GH secretion during sleep are of pathological significance; (3) disturbances of GH secretion might be diagnosed by measuring GH secretion during sleep rather than by using conventional stimulation tests; (4) a trial course of hGH treatment could be proposed in patients with both kinds of discrepancies between GH responses to stimuli and GH secretion during sleep.

Adolescent↗
PubMed1986

Transmembrane signals mediating neural peptide secretion: role of protein kinase C activators and arachidonic acid metabolites in luteinizing hormone-releasing hormone secretion.

The present experiments were designed to determine the effects of different activators of protein kinase C on the secretion of LHRH from median eminence nerve terminals incubated in vitro. The release of prostaglandin E2 (PGE2), a metabolite of arachidonic acid intimately involved in the secretion of LHRH, was also evaluated. Synthetic diacylglycerol [1,2-didecanoylglycerol (DiC10)] significantly enhanced PGE2 release in a concentration-dependent manner. Blockade of phospholipase A2 (PLA2) activity nullified this effect. LHRH release, on the other hand, was not increased by DiC10. However, in the presence of a lipoxygenase inhibitor, DiC10 produced a concentration-related increase in LHRH release, which paralleled that in PGE2. Phospholipase C (PLC) increased both PGE2 and LHRH secretion. Again, blockade of the lipoxygenase pathway enhanced the release of LHRH by PLC without affecting the stimulated secretion of PGE2. A phorbol ester, phorbol 12,13-dibutyrate (PDBu), markedly increased LHRH secretion while inducing a modest increase in PGE2 release. Both effects of PDBu were unaffected by lipoxygenase inhibition. DiC10, PDBu, and PLC significantly augmented LHRH secretion from tissues in which metabolism of arachidonic acid had been prevented by inhibition of both cyclooxygenase and lipoxygenase pathways, suggesting that activation of protein kinase C, independent of PLA2 activation, can lead to the secretion of this neural peptide. Some lipoxygenase metabolites had either no effect on [5- and 15-hydroxyeicosatetraenoic (5- and 15-HETE)] or induced a marginal stimulation of (12-HETE) LHRH release. At certain concentrations, 12-HETE enhanced the stimulatory effect of the phorbol ester on LHRH release. Our results suggest that activation of protein kinase C can stimulate LHRH secretion from nerve terminals in vitro and, further, that diacylglycerol may represent an important intracellular messenger participating in the events leading to LHRH secretion. In addition, stimulation with DiC10 and PLC uncovered inhibitory [unknown arachidonic acid metabolite(s) via lipoxygenase] and stimulatory (PGE2 via cyclooxygenase) pathways through with arachidonic acid metabolites may participate in the intracellular transduction of signals modulating neural peptide secretion.

Animals↗