To investigate the difference of biochemical characteristics on gsp positive and gsp negative growth hormone (GH) secreting pituitary tumors, 18 GH secreting pituitary tumors were examined for their clinical char...To investigate the difference of biochemical characteristics on gsp positive and gsp negative growth hormone (GH) secreting pituitary tumors, 18 GH secreting pituitary tumors were examined for their clinical characteristics and gsp oncogenes. All patients received the pituitary function combinative stimulating test. It was found that there were no difference in the sex, age, tumor size, course of disease and plasma basal GH levels with gsp positive and gsp negative patients. The plasma levels of PRL were increased in most patients (11/18), and the plasma levels of TSH in gsp positive patients were higher than those in gsp negative patients ( P <0.05). There was no significant difference in the responses to pituitary combinative stimulating test in gsp positive and gsp negative patients. It was concluded that there was little difference in the clinical biochemical characteristics of gsp positive with gsp negative GH secreting pituitary tumors.展开更多
Background Subclinical apoplexy of pituitary functional adenoma can cause spontaneous remission of hormone hypersecretion. The typical presence of pituitary growth hormone （GH） adenoma is gigantism and/or acromegaly...Background Subclinical apoplexy of pituitary functional adenoma can cause spontaneous remission of hormone hypersecretion. The typical presence of pituitary growth hormone （GH） adenoma is gigantism and/or acromegaly. We investigated the clinical characteristics of patients with spontaneous partial remission of acromegaly or gigantism due to subclinical apoplexy of GH adenoma. Methods Six patients with spontaneous remission of acromegaly or gigantism were enrolled. The clinical characteristics, endocrinological evaluation and imageological characteristics were retrospectively analyzed. Results In these cases, the initial clinical presences were diabetes mellitus or hypogonadism. No abrupt headache, vomiting, visual function impairment, or conscious disturbance had ever been complained of. The base levels of GH and insulin growth factor-1 （IGF-1） were normal or higher, but nadir GH levels were all still 〉1 μg/L in 75 g oral glucose tolerance test. Magnetic resonance imaging detected enlarged sella, partial empty sella and compressed pituitary. The transsphenoidal surgery was performed in 2 cases, and the other patients were conservatively managed. All the patients were in clinical remission. Conclusions When the clinical presences, endocrine evaluation, biochemical examination and imageology indicate spontaneous remission of GH hypersecretion in patients with gigantism or acromegaly, the diagnosis of subclinical apoplexy of pituitary GH adenoma should be presumed. To these patients, conservative therapy may be appropriate.展开更多
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 acrome...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 nuclear so far. It is necessary to investigate, at molecular level, the etiology of GH-PRL adenomas and its response to therapeutic agents.展开更多
Currently, the primary therapeutic strategy for most growth hormone-producing pituitary adenomas(GHPA) is surgery. Due to the invasiveness of GHPA, high recurrence has limited the benefit of complete adenoma removal s...Currently, the primary therapeutic strategy for most growth hormone-producing pituitary adenomas(GHPA) is surgery. Due to the invasiveness of GHPA, high recurrence has limited the benefit of complete adenoma removal surgery. Epidermal growth factor-like domain 7(EGFL7) is a secreted factor implicated in tumor angiogenesis, growth, invasiveness and metastasis in GHPA. Herein, we observed that the expression level of EGFL7 and p-EGFR in invasive GHPAwas much higher than that of non-invasive GHPA. The overexpression of EGFL7 was positively correlated with activation of EGFR(p-EGFR). Noticeably, EGFL7 knockdown significantly inhibited activation of EGFR signaling cascades, including p-ERGR, p-AKT and p-ERK. Further studies showed that EGFL7 knockdown or pharmacological inhibition of EGFR-pathway, using EGFR inhibitor Tyrphostin AG-1478, significantly suppressed migration and invasion of GH3 and GT1-1 cells. In summary, our findings suggest that EGFL7 is a key factor for regulation of EGFR signaling pathway and plays an important role in migration and invasion of invasive GHPA.展开更多
In order to investigate the relationship between abnormal intracellular signal transduction and tumorgenesis of human pituitary somatotrophinomas, the effects of protein kinase A (PKA) dependent growth hormone (GH) r...In order to investigate the relationship between abnormal intracellular signal transduction and tumorgenesis of human pituitary somatotrophinomas, the effects of protein kinase A (PKA) dependent growth hormone (GH) releasing hormone (GHRH) and protein kinase C (PKC) dependent GH releasing peptide (GHRP 6) on cAMP production were observed by using cell culture and biochemical methods, and the expression of the gsp oncogene was detected by using PCR and direct sequence assay methods in 11 patients with human pituitary somatotrophinomas. It was found that GHRP 6 exerted significant stimulatory effect on cAMP production by 2 gsp positive tumors and no effect on the gsp negative tumors. GHRP 6 could enhance the stimulation of cAMP production induced by GHRH in tumor without gsp oncogenes. It was suggested that both GHRH and GHRP 6 exert identical effects on human pituitary soamtotrophinomas, which was contributed to the cross talk between the two intracellular signal transduction pathways in pituitary cells.展开更多
Nowdays the application of immunohistochemical techniques and ultrastructuralanalysis and correlation with clinical and biochemical findings have led to a moredetailed functional classification,in which growth hormone...Nowdays the application of immunohistochemical techniques and ultrastructuralanalysis and correlation with clinical and biochemical findings have led to a moredetailed functional classification,in which growth hormone (GH)-producing andprolactin (PRL)-producing adenomas have been shown to comprise more than halfof pituitary adenomaso.Few immunoelectron microscopic studies on GH and PRLadenomas have been made,however,in limited cases so far,though a numberof authors have described the characteristics of pituitary adenomas by conventionalelectron microscopy.In addition to routine electron microscopy,immuno-.electron microscopical technique using protein A-gold probes was applied in展开更多
The effects of the novel GH-releasing hexapeptide, Hexarelin, on the secretion of GH in cultured human pituitary somatotrophinomas was further investigated. Hexarelin (20 nmol / L) strongly stimulated GH secretion, wh...The effects of the novel GH-releasing hexapeptide, Hexarelin, on the secretion of GH in cultured human pituitary somatotrophinomas was further investigated. Hexarelin (20 nmol / L) strongly stimulated GH secretion, which could be reduced by phloretin, but not by RP-cAMPS, an inhibitor of protein kinase A (PKA). (Ac-Tyr1, D-Arg 2 ) -GRF (1 - 29) -NH 2 failed t o block the effects of Hexarelin but completely abolished the stimulation of GH secretion exerted by GHRH. When added alone to somatotrophinoma cell cultures, Hexarelin had no effect on cAMP levels, but it potentiated the stimulatory effects of GHRH. These results demonstrated that Hexarelin could directly stimulate GH secretion by human pituitary somatotrophs PKC-dependently, which might be contributed to the activation of the PI transduction system. In addition, Hexarelin could interact with GHRH on the adenylyl cyclase system.展开更多
In order to describe the magnetic resonance imaging (MRI) findings in hypothaiamic-pituitary area and its clinical relevance in patients with idiopathic growth hormone deficiency (IGHD), the MR imagings of 26 patients...In order to describe the magnetic resonance imaging (MRI) findings in hypothaiamic-pituitary area and its clinical relevance in patients with idiopathic growth hormone deficiency (IGHD), the MR imagings of 26 patients with IGHD were analyzed. On MRI, 24 out of 26 cases (92. 3%) showed apparent pituitary upper margin depresslon t 8 out of 26 cases (30. 8%) showed defmlte pituitary stalk transeetlon; 22 out of 26 cases (84. 6%) showed absence of the normal posterior pituitary bright spot. The bright lipidlike signal on TIW1 images at the median eminence distal to the breaking point (so-called ectople posterior lobe) was found in 4 out of 26 cases (15.4%). According to the MRI findings of iehe pituitary stalks, the 26 cases were divided into three groups; group A of 8 cases (31%) characterized by the definite transaction of stalk; group B of 13 cases (50%) defined by the possible stalk transection; and group C of 5 eases (19%) with no definite stalk transection. MRI findings were consistent with the clinical and endocrine tests. The stalk transection was staristically significantly difference in insulin test, L-dopa/p test, and height standard deviation score (P<0. 05). The MRI of hypothalamic-pltuitary area may differentiate partial IGHD form stalk-transected,doubtful transection and without transection.展开更多
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 α subunit o...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 α subunit of the stimulatory GTP binding protein, G s (G sα). 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.展开更多
AIM: The pathogenesis of hypogonadism in liver cirrhosis is not well understood. Previous results from our laboratory showed that IGF-1 deficiency might play a pathogenetic role in hypogonadism of cirrhosis. The admin...AIM: The pathogenesis of hypogonadism in liver cirrhosis is not well understood. Previous results from our laboratory showed that IGF-1 deficiency might play a pathogenetic role in hypogonadism of cirrhosis. The administration of IGF-1 for a short period of time reverted the testicular atrophy associated with advanced experimental cirrhosis.The aim of this study was to establish the historical progression of the described alterations in the testes,explore testicular morphology, histopathology, cellular proliferation, integrity of testicular barrier and hypophysogonadal axis in rats with no ascitic cirrhosis.METHODS: Male Wistar rats with histologically-proven cirrhosis induced with carbon tetrachloride (CC14) for 11 wk,were allocated into two groups (n = 12, each) to receive recombinant IGF-1 (2 μg/100 g·d, sc) for two weeks or vehicle. Healthy rats receiving vehicle were used as control group (n = 12).RESULTS: Compared to controls, rats with compensated cirrhosis showed a normal testicular size and weight and very few histopathological testicular abnormalities.However, these animals showed a significant diminution of cellular proliferation and a reduction of testicular transferrin expression. In addition, pituitary-gonadal axis was altered, with significant higher levels of FSH (P<0.001 vs controls) and increased levels of LH in untreated cirrhotic animals. Interestingly, IGF-1 treatment normalized testicular transferrin expression and cellular proliferation and reduced serum levels of LH (P = ns vs controls, and P<O.01 vs untreated cirrhotic group).CONCLUSION: The testicular barrier is altered from an early stage of cirrhosis, shown by a reduction of transferrin expression in Sertoli cells, a diminished cellular proliferation and an altered gonadal axis. The treatment with IGF-1 could be also useful in this initial stage of testicular disorder associated with compensated cirrhosis.展开更多
基金This project was supported by a grant from the National Natural Sciences Foundation of China(No.396 70 736 )
文摘To investigate the difference of biochemical characteristics on gsp positive and gsp negative growth hormone (GH) secreting pituitary tumors, 18 GH secreting pituitary tumors were examined for their clinical characteristics and gsp oncogenes. All patients received the pituitary function combinative stimulating test. It was found that there were no difference in the sex, age, tumor size, course of disease and plasma basal GH levels with gsp positive and gsp negative patients. The plasma levels of PRL were increased in most patients (11/18), and the plasma levels of TSH in gsp positive patients were higher than those in gsp negative patients ( P <0.05). There was no significant difference in the responses to pituitary combinative stimulating test in gsp positive and gsp negative patients. It was concluded that there was little difference in the clinical biochemical characteristics of gsp positive with gsp negative GH secreting pituitary tumors.
文摘Background Subclinical apoplexy of pituitary functional adenoma can cause spontaneous remission of hormone hypersecretion. The typical presence of pituitary growth hormone （GH） adenoma is gigantism and/or acromegaly. We investigated the clinical characteristics of patients with spontaneous partial remission of acromegaly or gigantism due to subclinical apoplexy of GH adenoma. Methods Six patients with spontaneous remission of acromegaly or gigantism were enrolled. The clinical characteristics, endocrinological evaluation and imageological characteristics were retrospectively analyzed. Results In these cases, the initial clinical presences were diabetes mellitus or hypogonadism. No abrupt headache, vomiting, visual function impairment, or conscious disturbance had ever been complained of. The base levels of GH and insulin growth factor-1 （IGF-1） were normal or higher, but nadir GH levels were all still 〉1 μg/L in 75 g oral glucose tolerance test. Magnetic resonance imaging detected enlarged sella, partial empty sella and compressed pituitary. The transsphenoidal surgery was performed in 2 cases, and the other patients were conservatively managed. All the patients were in clinical remission. Conclusions When the clinical presences, endocrine evaluation, biochemical examination and imageology indicate spontaneous remission of GH hypersecretion in patients with gigantism or acromegaly, the diagnosis of subclinical apoplexy of pituitary GH adenoma should be presumed. To these patients, conservative therapy may be appropriate.
文摘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 nuclear so far. It is necessary to investigate, at molecular level, the etiology of GH-PRL adenomas and its response to therapeutic agents.
基金supported by the National Natural Science Foundation of China (81502154)Research Special Fund For Public Welfare Industry of Health of China (201402008)National High Technology Research and Development Program of China (2015AA020504)
文摘Currently, the primary therapeutic strategy for most growth hormone-producing pituitary adenomas(GHPA) is surgery. Due to the invasiveness of GHPA, high recurrence has limited the benefit of complete adenoma removal surgery. Epidermal growth factor-like domain 7(EGFL7) is a secreted factor implicated in tumor angiogenesis, growth, invasiveness and metastasis in GHPA. Herein, we observed that the expression level of EGFL7 and p-EGFR in invasive GHPAwas much higher than that of non-invasive GHPA. The overexpression of EGFL7 was positively correlated with activation of EGFR(p-EGFR). Noticeably, EGFL7 knockdown significantly inhibited activation of EGFR signaling cascades, including p-ERGR, p-AKT and p-ERK. Further studies showed that EGFL7 knockdown or pharmacological inhibition of EGFR-pathway, using EGFR inhibitor Tyrphostin AG-1478, significantly suppressed migration and invasion of GH3 and GT1-1 cells. In summary, our findings suggest that EGFL7 is a key factor for regulation of EGFR signaling pathway and plays an important role in migration and invasion of invasive GHPA.
基金This project was supported by the grants from National Natural Science Foundation of China (No. 396 70 736 ) Deutsche Gesel
文摘In order to investigate the relationship between abnormal intracellular signal transduction and tumorgenesis of human pituitary somatotrophinomas, the effects of protein kinase A (PKA) dependent growth hormone (GH) releasing hormone (GHRH) and protein kinase C (PKC) dependent GH releasing peptide (GHRP 6) on cAMP production were observed by using cell culture and biochemical methods, and the expression of the gsp oncogene was detected by using PCR and direct sequence assay methods in 11 patients with human pituitary somatotrophinomas. It was found that GHRP 6 exerted significant stimulatory effect on cAMP production by 2 gsp positive tumors and no effect on the gsp negative tumors. GHRP 6 could enhance the stimulation of cAMP production induced by GHRH in tumor without gsp oncogenes. It was suggested that both GHRH and GHRP 6 exert identical effects on human pituitary soamtotrophinomas, which was contributed to the cross talk between the two intracellular signal transduction pathways in pituitary cells.
文摘Nowdays the application of immunohistochemical techniques and ultrastructuralanalysis and correlation with clinical and biochemical findings have led to a moredetailed functional classification,in which growth hormone (GH)-producing andprolactin (PRL)-producing adenomas have been shown to comprise more than halfof pituitary adenomaso.Few immunoelectron microscopic studies on GH and PRLadenomas have been made,however,in limited cases so far,though a numberof authors have described the characteristics of pituitary adenomas by conventionalelectron microscopy.In addition to routine electron microscopy,immuno-.electron microscopical technique using protein A-gold probes was applied in
基金a grant from the foundationof Health Ministry (No. 96-2-14) and Educational Committee of China (No. 97-436).
文摘The effects of the novel GH-releasing hexapeptide, Hexarelin, on the secretion of GH in cultured human pituitary somatotrophinomas was further investigated. Hexarelin (20 nmol / L) strongly stimulated GH secretion, which could be reduced by phloretin, but not by RP-cAMPS, an inhibitor of protein kinase A (PKA). (Ac-Tyr1, D-Arg 2 ) -GRF (1 - 29) -NH 2 failed t o block the effects of Hexarelin but completely abolished the stimulation of GH secretion exerted by GHRH. When added alone to somatotrophinoma cell cultures, Hexarelin had no effect on cAMP levels, but it potentiated the stimulatory effects of GHRH. These results demonstrated that Hexarelin could directly stimulate GH secretion by human pituitary somatotrophs PKC-dependently, which might be contributed to the activation of the PI transduction system. In addition, Hexarelin could interact with GHRH on the adenylyl cyclase system.
文摘In order to describe the magnetic resonance imaging (MRI) findings in hypothaiamic-pituitary area and its clinical relevance in patients with idiopathic growth hormone deficiency (IGHD), the MR imagings of 26 patients with IGHD were analyzed. On MRI, 24 out of 26 cases (92. 3%) showed apparent pituitary upper margin depresslon t 8 out of 26 cases (30. 8%) showed defmlte pituitary stalk transeetlon; 22 out of 26 cases (84. 6%) showed absence of the normal posterior pituitary bright spot. The bright lipidlike signal on TIW1 images at the median eminence distal to the breaking point (so-called ectople posterior lobe) was found in 4 out of 26 cases (15.4%). According to the MRI findings of iehe pituitary stalks, the 26 cases were divided into three groups; group A of 8 cases (31%) characterized by the definite transaction of stalk; group B of 13 cases (50%) defined by the possible stalk transection; and group C of 5 eases (19%) with no definite stalk transection. MRI findings were consistent with the clinical and endocrine tests. The stalk transection was staristically significantly difference in insulin test, L-dopa/p test, and height standard deviation score (P<0. 05). The MRI of hypothalamic-pltuitary area may differentiate partial IGHD form stalk-transected,doubtful transection and without transection.
文摘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 α subunit of the stimulatory GTP binding protein, G s (G sα). 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.
基金Supported by the Spanish Program I+D,SAF 99/0072 and SAF2001/1672
文摘AIM: The pathogenesis of hypogonadism in liver cirrhosis is not well understood. Previous results from our laboratory showed that IGF-1 deficiency might play a pathogenetic role in hypogonadism of cirrhosis. The administration of IGF-1 for a short period of time reverted the testicular atrophy associated with advanced experimental cirrhosis.The aim of this study was to establish the historical progression of the described alterations in the testes,explore testicular morphology, histopathology, cellular proliferation, integrity of testicular barrier and hypophysogonadal axis in rats with no ascitic cirrhosis.METHODS: Male Wistar rats with histologically-proven cirrhosis induced with carbon tetrachloride (CC14) for 11 wk,were allocated into two groups (n = 12, each) to receive recombinant IGF-1 (2 μg/100 g·d, sc) for two weeks or vehicle. Healthy rats receiving vehicle were used as control group (n = 12).RESULTS: Compared to controls, rats with compensated cirrhosis showed a normal testicular size and weight and very few histopathological testicular abnormalities.However, these animals showed a significant diminution of cellular proliferation and a reduction of testicular transferrin expression. In addition, pituitary-gonadal axis was altered, with significant higher levels of FSH (P<0.001 vs controls) and increased levels of LH in untreated cirrhotic animals. Interestingly, IGF-1 treatment normalized testicular transferrin expression and cellular proliferation and reduced serum levels of LH (P = ns vs controls, and P<O.01 vs untreated cirrhotic group).CONCLUSION: The testicular barrier is altered from an early stage of cirrhosis, shown by a reduction of transferrin expression in Sertoli cells, a diminished cellular proliferation and an altered gonadal axis. The treatment with IGF-1 could be also useful in this initial stage of testicular disorder associated with compensated cirrhosis.
