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T Lei

Publications and source records attributed to T Lei.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effects of the novel GH secretogogue, hexarelin on GH secretion and phosphatidylinositol hydrolysis by human pituitary somatotrophinomas in cell culture.

The effects of the novel GH-releasing hexapeptide, Hexarelin, on cultured human pituitary somatotrophinomas were investigated. Hexarelin (0.01-100 nmol/L) dose-dependently stimulated GH secretion up to 4.6-fold. Maximal effects occurred with 10 nmol/L. These effects were very similar to those observed with GHRP-6. The effects of Hexarelin were reduced by phloretin, an inhibitor of protein kinase C (PKC). The rate of phosphatidylinositol (PI) hydrolysis was markedly increased by Hexarelin in a dose-dependent manner. These results demonstrated that Hexarelin could directly stimulate GH secretion by human pituitary somatotrophs in a PKC-dependent manner, probably via activation of the PI transduction system.

Adenoma↗
PubMed1999

TPA enhances growth hormone (GH) secretion effect of GH-releasing hormone (GHRH) by human gsp-positive pituitary somatotrophinomas.

In recent years, one of the most exciting advances in the researches of pituitary adenomas is the discovery that 30%-40% of human pituitary somatotrophinomas carry somatic mutations of the gene for the alpha-subunit of the stimulatory GTP-binding protein, Gs (Gs alpha). These mutations, termed gsp oncogenes, may play an important role in the tumorigenesis of pituitary adenomas. Of 10 somatotrophinomas examined, 3 (30%) were proved to be gsp positive, as determined by sequence analysis of DNA generated by the polymerase chain reaction (PCR). GHRH exerted a significant stimulatory effect on GH secretion in 2 of 3 gsp-positive and 4 of 7 gsp-negative tumors. Moreover, phorbol ester, 1, 2-tetradecanoylphorbol-13-acetate (TPA), enhanced stimulation of lated the GH secretion effect exerted by GHRH in gsp-positive somatotrophinomas, whereas this effect was not observed in gsp-negative tumors. This result suggests that the protein kinase C signal system as well as adenylyl cyclase-cAMP-protein kinase A intracellular signal transduction system plays a pivotal role in GH secretory control of GHRH, which may work together via a cross-talk mechanism.

Adenoma↗
PubMed1998

Hormone secretion by cell culture of human GH-PRL secreting pituitary adenomas: effects of bromocriptine.

Dopamine agonists effectively reduce the secretion of prolactin (PRL) in the great majority of prolactinomas and reduce the bulk of the adenomas, as well as have partial therapeutic effect on some patients with acromegaly. The inhibitory effect of bromocriptine (BC), a dopamine agonist, on growth hormone (GH) and PRL secretion of dispersed cells from the pituitary adenomas of 16 cases of acromegaly, which secret GH and PRL simultaneously, were evaluated in vitro. The significant inhibitory effects of BC on PRL secretion were found in 12 cases. It was also found that PRL secretion was strongly inhibited when GH was suppressed; on the contrary, when GH secretion was not suppressed, the production of PRL was not or weakly inhibited. The exact mechanism of the effects is unclear so far. It is necessary to investigate, at molecular level, the etiology of GH-PRL adenomas and its response to therapeutic agents.

Adenoma↗
PubMed1998

Overexpression of stimulatory G protein alpha-subunit is a hallmark of most human somatotrophic pituitary tumours and is associated with resistance to GH-releasing hormone.

The heterotrimeric Gs protein-adenylyl cyclase (AC) cascade plays a pivotal role in controlling hormone secretion by endocrine glands. Consequently, deficiency of the alpha-subunit of Gs leads to endocrine hypofunction and hypoplasia in the affected cells whereas AC hyperactivity results from activating point mutations within the Gs-alpha gene. The latter, termed gsp oncogenes, are found primarily in a subset of growth hormone (GH)-secreting human pituitary tumours (somatotrophinomas) and are thus associated with excessive GH secretion. We present here evidence that another type of defect in human somatotrophinomas may be overexpression of the Gs-alpha subunit. Immunohistochemistry using an antibody against recombinant human Gs-alpha revealed high levels of expression in 25 of 39 somatotrophinomas but weak staining in normal human pituitary cells. These results were confirmed by Western blot analysis. Additionally, cholera toxin-mediated ADP-ribosylation in the presence of 32P-labelled NAD+ resulted in an autoradiographic signal intensity which correlated directly with magnitude of immunostaining and amount of antigen shown by Western blot analysis, providing evidence for overexpression of functionally active subunit. Finally, reconstitution assays were applied and directly demonstrated the increased activity of overexpressed Gs-alpha. In vivo, the effect of Gs-alpha on AC activity may be partially counterregulated by high levels of inhibitory G protein that also occurred in these tumours. In culture, GH-releasing hormone (GHRH) had markedly reduced effects on GH secretion by somatotrophinomas exhibiting Gs-alpha overexpression, whereas powerful stimulation occurred in weakly staining tumours. In contrast to these observations with Gs-alpha, immunostaining for the phospholipase C-coupled G11-alpha subunit was relatively weak in all somatotrophinomas studied and synthetic GH-releasing peptide, which acts via a specific G11-coupled receptor, led to powerful and consistent stimulation of GH secretion by different tumours. These results indicate that Gs-alpha overexpression is associated with dysfunction in hormone secretion by some somatotrophinomas.

Adenoma↗
PubMed1997

Relationship between invasiveness of pituitary somatotrophinomas and structural abnormalities of protein kinase C gene in human.

The potential role of the protein kinase C (PKC) transduction system in controlling proliferation of human pituitary somatotrophinomas was investigated. Twenty somatotrophinomas were studied using PCR and direct sequencing methods. No point mutation within the alpha PKC gene, previously thought to be associated with invasive pituitary tumors, was found in any of the 20 somatotrophinomas. It is concluded that PKC transduction system may play an important role in controlling pituitary somatotrophinoma proliferation, but there is no correlation between invasiveness and the previously reported alpha PKC gene mutation.

Adenoma↗
PubMed1997

Relationship between GHRP-6 and TPA in the regulation of growth hormone secretion by human pituitary somatotrophinomas.

Growth hormone releasing peptide (GHRP-6) is a synthetic hexapeptide which specifically stimulates secretion of growth hormone (GH) by pituitary somatotrophs. Phorbel ester, 1, 2 tetradecanoylphorbol 13 acetate (TPA) can also stimulate releasing of GH. The precise intracellular mechanism has not been entirely deciphered. We used cell cultures of human pituitary somatotrophinomas to investigate the relation between GHRP-6 and TPA on membrane phosphatidylinositol (PI) turnover and GH secretion. The results showed that the working mechanisms of GHRP-6 and TPA are not identical, although they all can stimulate GH secretion in human pituitary somatotrophinomas. This indicates that PI-PKC signal transduction system may play a crucial role in the regulation of GH secretion.

Adenoma↗
PubMed1997

Human meningiomas possess muscarinic acetylcholine receptors: stimulation of phosphatidylinositol turnover by carbachol.

The effect of carbachol, an acetylcholine receptor agonist, on rate of phosphatidylinositol (PI) turnover in cultured human meningioma cells was investigated. Exposure of meningioma cells for 2 h to carbachol (3.12-200 mumol/L) resulted in a dose-dependent stimulation of PI turnover to a maximum of 5.5-fold over basal controls. A time course study showed stimulation of IP3 formation after 30 s followed by increases in IP1 and IP2. The stimulatory effect of carbachol on PI turnover was completely abolished by the muscarinic receptor antagonist, atropine, but was unaltered by the nicotinic antagonist, hexamethonium. Reverse-transcription of meningioma-derived RNA into cDNA followed by amplification by the polymerase chain reaction using specific primers revealed presence of ml type muscarinic receptor mRNA. These results provide evidence that human meningioma cells possess muscarinic acetylcholine receptors the activation of which leads to PI hydrolysis.

Atropine↗
PubMed1997

[Resonance Raman spectra of transition metal Mn(III), Fe(III), Rh(III), Pd(II) porphyrin complexes].

The resonance Raman spectra of Mn(III), Rh(III), Fe(III), Pd(II) protoporphyrin IX-dimethylester (PP) and tetra-phenylporphyrin (TPP) complexes were reported. The difference of their structure-sensitive band frequency was a result of the interaction of different metal ions' outer d electrons with the electrons of the porphyrin ring. As well the effects of different porphyrin rings and their substituts on the structure-sensitive bands were discussed in this paper.

Iron↗
PubMed1996

Molecular biology of growth-hormone-secreting human pituitary tumours: biochemical consequences and potential clinical significance.

Molecular biological studies have revealed that 30-40% of GH-secreting human pituitary tumours, associated with acromegaly, harbour single-base missense mutations within the Gs alpha gene, termed gsp oncogenes. In addition, a large proportion of GH-secreting tumours inappropriately express the GH-releasing factor (GRF) gene. Gsp-oncogenes result in elevated adenylyl cyclase activity with consequent abnormally high cAMP production. In culture, GH-secreting tumours expressing gsp oncogenes respond more efficiently to the somatostatin analogue, octreotide (SMS), raising the possibility that acromegalics harbouring gsp-positive tumours may be those who optimally benefit from SMS therapy. Inappropriate expression of GRF may result in abnormal presence of a positive autocrine feedback loop, in which secreted GRF acts on the same cells to promote cellular proliferation and GH secretion. Blockade of GRF mRNA translation by means of anti-sense oligonucleotide approaches may prove to be of value in inhibiting tumour function.

Acromegaly↗
PubMed1996

Relationship between cAMP induced inhibition of human meningioma cell proliferation and autocrine secretion of interleukin-6.

Previous studies have suggested that activation of the adenylyl cyclase - cAMP system in meningiomas results in decreased mitosis. We have used meningioma cell culture to further investigate this phenomenon and to examine the potential role played by interleukin-6 (IL6). Incubation of cultured meningioma cells for 4-6 days with cholera toxin and theophylline, both of which increase intracellular cAMP levels, markedly stimulated IL6 secretion and inhibited cell growth rate. Similar effects were observed with 8-bromo-cAMP. In contrast, a neutralising polyclonal antibody against IL6 significantly stimulated meningioma proliferation and reduced the inhibitory effects of 8-bromo-cAMP. These results support the concept that IL6 acts as an autocrine / paracrine inhibitory factor for meningioma proliferation, and that the inhibition exerted by elevated intracellular cAMP levels may be at least partially mediated via increased secretion of the cytokine.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1996

Relationship between protein kinase C and adenylyl cyclase activity in the regulation of growth hormone secretion by human pituitary somatotrophinomas.

OBJECTIVE: To determine the potential role of protein kinase C (PKC) and its relationship to adenylyl cyclase activity in controlling growth hormone (GH) secretion by human pituitary somatotrophinomas. METHODS: Twenty-eight somatotrophinomas were placed into cell culture, and the in vitro effects of the PKC activator 12-O-tetradecanoylphorbol 13-acetate (TPA) and the PKC inhibitor staurosporine on basal and GH-releasing hormone (GHRH)-stimulated GH secretion were examined. In addition, the influence of chronic exposure of cultured somatotrophinoma cells to TPA on the rate of inositol 1,4,5-trisphosphate production was determined. Each tumor was assessed for the presence of gsp oncogenes, and thus constitutive adenylyl cyclase activity, by direct sequence analysis of polymerase chain reaction-generated deoxyribonucleic acid. GH secretory responses of tumors with and without these oncogenes were compared. RESULTS: TPA consistently stimulated GH secretion by cultured somatotrophinoma cells. There was no difference in response between somatotrophinomas with and without gsp oncogenes, and the effects did not correlate with the variable stimulation exerted by GHRH. Tumors in which GHRH had no significant effect nevertheless responded to TPA. In combination, TPA and GHRH exerted additive stimulation. TPA treatment of cultured somatotrophinoma cells eventually resulted in suppression of inositol 1,4,5-trisphosphate production, probably reflecting down-regulation of membrane phosphatidylinositol hydrolysis, a second messenger system that also generates the endogenous PKC activator diacylglycerol. GHRH had no effect on phosphatidylinositol hydrolysis. In contrast to the effects of TPA, the PKC inhibitor staurosporine tended to reduce GH secretion, although this effect was not observed in all tumors examined. As with TPA, the effects of staurosporine did not correlate with presence or absence of gsp oncogenes. Furthermore, staurosporine did not reduce the stimulatory effects exerted by GHRH on GH secretion. CONCLUSION: These results demonstrate a role for the phosphatidylinositol-PKC second messenger cascade in controlling GH secretion by human pituitary somatotrophinomas. The results also show that the system operates relatively independent of intracellular adenylyl cyclase and, thus, protein kinase A.

Adenoma↗
PubMed1996

Protein kinase C-dependent growth hormone releasing peptides stimulate cyclic adenosine 3',5'-monophosphate production by human pituitary somatotropinomas expressing gsp oncogenes: evidence for crosstalk between transduction pathways.

The effects of the synthetic GH-releasing peptides, GHRP-2 and GHRP-6, on phosphatidylinositol (PI) hydrolysis and cAMP production have been examined in human pituitary somatotropinomas with and without adenylyl cyclase-activating gsp oncogenes. Both peptides dose-dependently stimulated the rate of PI hydrolysis and GH secretion by cell cultures of both types of somatotropinoma. GHRP-2 was considerably more potent than GHRP-6. The effects on GH secretion were reduced or abolished by phloretin, an inhibitor of protein kinase C, and W7, an inhibitor of calmodulin. However, antagonism of the GHRH-receptor and of protein kinase A with (N-Ac-Tyr1,D-Arg2)GRF-(1-29)-NH2 and Rp-adenosine-3',5'-cyclic monophosphothioate, respectively, did not alter the stimulatory effects of GHRP-2 and GHRP-6 on GH secretion. The effect of GHRP-2 and/or GHRP-6 on cAMP production was studied in 15 tumors, seven of which possessed constitutive adenylyl cyclase activity as evidenced by presence of gsp oncogenes. Both peptides stimulated cAMP production in the latter but not former types of tumor. Moreover, GHRP-2 and GHRP-6 potentiated the stimulation of cAMP production induced by GHRH and pituitary adenylate cyclase-activating polypeptide in tumors without gsp oncogenes. These results demonstrate that GHRP-2 and GHRP-6 exert identical effects on human pituitary somatotropinomas, except for differences in potency. Additionally, under conditions of adenylyl cyclase activity above basal levels (i.e. through stimulation of G2-protein coupled receptors or because of gsp oncogene expression), cAMP production can be increased even further by GHRP, providing evidence for cross-talk between the PI and adenylyl cyclase transduction systems in pituitary cells.

Base Sequence↗
PubMed1996

[A study on glycosylated high density lipoprotein and its binding to receptors in human lung fibroblasts in diabetic patients].

In order to know the glycosylation of high density lipoprotein (HDL) and its specific binding to human lung fibroblasts (HLF) receptors in diabetic patients, the glycosyflation of HDL in diabetic group I (HbAlc < 7.6%) and II (HNbAlc > 9.6%) and a control group were measured with fluorimetry. The hydrazides in carbonyl radical of HDL in the three groups were conjugated with horadish peroxidase (HRP). The specific binding of HDL-HRP to HLF receptors was measured with enzyme linked immunoreceptor assay. The results showed that the glycosylated amount of HDl in group I, II and the control group was 39.26 +/- 8.10, 72.96 +/- 6.40 and 20.40 +/- 1.10 glycogroups/HDL respectively. The surface specific binding of HDL-HRP to HLF receptors in medium with high cholesterol was significantly greater than that in medium without cholesterol (P < 0.01). The surface specific binding of HDL-HRP to HLF receptors in group I and II was significantly lower than that in the control group (P < 0.01) and that in group II was significantly lower than in group I (P < 0.01). The results indicate glycosylated HDL in diabetic patients is increased but its specific binding to HLF receptors is decreased as compared with that in control subjects.

Aged↗
PubMed1995

The growth hormone secretagogue, L-692,429, induces phosphatidylinositol hydrolysis and hormone secretion by human pituitary tumors.

L-692,429 is a non-peptidyl GH secretagogue. We examined the effects of L-692,429 on cultured human pituitary tumors removed from patients with acromegaly. Dose-dependent stimulation of GH secretion was observed, with 1 mumol/L leading to 2 or 3-fold increases. Prolactin (PRL) secretion by a mixed somatotrophic-lactotrophic tumor was also stimulated. The effects of L-692,429 were abolished by phloretin and W7 but not Rp-cAMPS. Rate of phosphatidylinositol turnover was markedly increased up to 3-fold by L-692,429. These results show that L-692,429 increases hormone secretion by human pituitary cells via a protein kinase C and Ca2+ dependent mechanism.

Acromegaly↗
PubMed1995

Biochemical characteristics of human pituitary somatotropinomas with and without gsp mutations: in vitro cell culture studies.

Gsp oncogenes are present in about 40% of somatotropinomas. They result in excessive cAMP production and have been proposed to be the cause of increased GH secretion. We have used in vitro cell culture to compare the biochemical characteristics of somatotropinomas with and without gsp oncogenes (gsp-positive and gsp-negative tumors, respectively). Of 30 somatotropinomas examined, 10 proved to be gsp positive, as determined by sequence analysis of DNA generated by the polymerase chain reaction. The somatostatin analog, octreotide, powerfully inhibited GH secretion by gsp-positive somatotropinomas, but had no effect on 8 of 13 gsp-negative tumors. Five of 20 gsp-negative and 4 of 10 gsp-positive tumors failed to respond to GHRH, whereas stimulatory effects ranging from 37-500% increases in GH secretion occurred in the remainder. However, strong stimulation (> 4-fold) occurred only in 5 of the gsp-negative tumors. The basal phosphatidylinositol turnover rate was elevated in about 25% of gsp-negative somatotropinomas. These results demonstrate similar and highly variable effects of GHRH on both types of somatotropinoma, whereas the absence of gsp oncogenes is often associated with resistance to octreotide. The phosphatidylinositol turnover data suggest that defects within this second messenger system may be present in a subset of somatotropinomas without gsp oncogenes.

Base Sequence↗
PubMed1995

Growth hormone releasing peptide (GHRP-6) stimulates phosphatidylinositol (PI) turnover in human pituitary somatotroph cells.

Growth hormone releasing peptide (GHRP-6) is a synthetic hexapeptide which specifically stimulates secretion of growth hormone (GH) by pituitary somatotrophs. The precise intracellular mechanism by which this is achieved has not been deciphered although it is known to involve protein kinase C (PKC) and Ca2+ but to be cAMP-independent. We have used cell cultures of human pituitary somatotrophinomas to demonstrate powerful effects of GHRP-6 on membrane phosphatidylinositol (PI) turnover, a second messenger system which leads to activation of PKC and mobilisation of intracellular Ca2+ reserves. Incubation of somatotrophinoma cells with GHRP-6 led to a dose-dependent stimulation of rate of PI turnover. GH secretion was increased in parallel. Effects were discernable after only 15 minutes incubation and rose to a maximum at 2 hours. PI turnover was stimulated by GHRP-6 in 8 of 8 tumours examined, effects ranging from 2.1 - 7.9 fold increases. Stimulation of GH secretion by GHRP-6 was independent of presence of gsp oncogenes, emphasising the cAMP-independent nature of its effects. These results provide evidence that the GH-stimulatory effects of GHRP-6 are achieved through activation of the PI second messenger system and thus support earlier findings that PKC and Ca2+ play central roles in mediating the effects of GHRP-6.

Calcium↗
PubMed1994

Poliomyelitis surveillance in Shandong Province, China, 1990-92.

In Shandong Province, China, programmes were initiated in 1991 for mass immunization against poliomyelitis and for the immediate reporting of acute flaccid paralysis (AFP). The incidence of non-poliomyelitis AFP was found to be 0.46-0.61 cases per 100,000 children per annum. It appeared that illness resembling the Guillain-Barré syndrome was underreported. The incidence of such illness peaked among children aged 2-3 years. Although laboratory investigations have improved, in 1992 they were still inadequate in nearly a third of confirmed poliomyelitis cases. As the prevalence of wild poliovirus declines in China, reliable laboratory support needs to be established and adequately sensitive and specific AFP surveillance be developed if poliomyelitis is to be eradicated.

Adolescent↗