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
AIM: To investigate the influencing factors of visual field improvement after trans-sphenoidal resection of pituitary macroadenomas. METHODS: This retrospective cohort study included 201 patients (366 eyes) with visua...AIM: To investigate the influencing factors of visual field improvement after trans-sphenoidal resection of pituitary macroadenomas. METHODS: This retrospective cohort study included 201 patients (366 eyes) with visual field defect induced by pituitary macroadenomas. All of them were treated with trans-sphenoidal surgery. Ophthalmologic evaluation, best -corrected visual acuity (BCVA), and visual field examination were performed before and 3mo after surgery. BCVA, visual field defect index mean deviation (MD), duration of symptoms, age, sex, and volume of tumors were compared. Expression of vascular endothelial growth factor (VEGF) and Ki-67 of tumor tissue were detected by immunohistochemical technique. RESULTS: The mean age of patients was 44.23 +/- 1.29y. Ninety -three patients were female and 108 were male. The mean tumor volume was 14.36 +/- 6.23 cm(3). The mean duration of preoperative symptoms was 11.50 +/- 0.88mo. Mean preoperative MD was -17.50 +/- 0.82 dB. Mean Preoperative visual acuity was 0.64 +/- 0.04. Postoperative visual field improved in 270 (73.77%) eyes, unchanged in 96 (26.23%) eyes. Multivariate logistic regression displayed that the factors independently influencing visual field improvement were young age (OR=1.71, 95%CI: 1.325-2.387, P=0.013), low preoperative MD absolute value (OR=1.277, 95%CI: 1.205-1.355, P<0.001), small volume of tumor (OR=1.458, 95%CI: 1.060-4.289, P<0.001), low expression of VEGF in tumor tissue (OR=1.554, 95%CI: 1.089-2.457, P=0.022), and low expression of Ki-67 in tumor tissue (OR=1.552, 95%CI: 1.161-2.847, P=0.026). CONCLUSION: After pituitary macroadenomas trans sphenoidal resection, the independent influencing factors of the visual fields recovery were low preoperative MD absolute value, young age, small volume of tumor, and expression levels of VEGF/Ki-67.展开更多
To investigate effect of the soluble epidermal growth factor receptor (sEGFR/sErbB1) level in the periph-eral blood in development, invasiveness, apoplexy of each type of pituitary tumor. Methods The sEGFR level was d...To investigate effect of the soluble epidermal growth factor receptor (sEGFR/sErbB1) level in the periph-eral blood in development, invasiveness, apoplexy of each type of pituitary tumor. Methods The sEGFR level was determined in peripheral serum from 190 patients with pituitary diseases by enzyme linked immunosobent assay. The sEGFR levels were measured in 10 pituitary Rathke’s pouch, 18 pituitary hyperplasia, 161 pituitary adenomas including 30 microadenomas, 83 large adenomas, 48 giant adenomas, 1 pituitary carcinoma, and 28 hea-lthy controls. Results In the patients with pituitary hyperplasia, microadenoma, large adenoma, giant adenoma, and pituitary carci-noma, the sEGFR level was 188.92 ± 32.62, 209.83 ± 19.01, 333.20 ± 69.33, 405.85 ± 37.38, and 617.45 fmol/mL indepen-dently. They were all significantly higher than patients with pituitary Rathke’s pouch (156.78 ± 18.24 fmol/mL, P < 0.001) and healthy control group (159.11 ± 40.50 fmol/mL, P < 0.05). The sEGFR level in pituitary carcinoma was higher than pi-tuitary adenoma. In patients with pituitary adenoma, the sEGFR level was positive correlated to the size of pituitary adeno-mas (r = 0.998), the significant difference was observed for the sEGFR level in each group of the patients with pituitary adenomas (P < 0.001). Furthermore, in patients with pituitary ACTH-secreting microadenomas, the serum sEGFR levels in invasiveness (295.00 ± 77.80 fmol/mL) was higher than that in non-invasiveness (210.60 ± 16.4 fmol/mL, P < 0.05). In pati-ents with pituitary ACTH-secreting, PRL-secreting, GH-secreting, and non-functioning large adenomas, the serum sEGFR levels in invasiveness (407.86 ± 28.50, 399.25 ± 30.10, 386.00 ± 13.08, and 369.25 ± 36.70 fmol/mL) was higher than that in non-invasiveness (335.25 ± 63.49, 300.64 ± 47.57, 297.00 ± 61.93, and 269.30 ± 25.68 fmol/mL) respectively (P < 0.05). In patients with invasive pituitary PRL-secreting, GH-secreting, and non-functioning giant adenomas, the serum sEGFR levels not significantly different in between invasiveness (417.50 ± 35.94, 409.50 ± 69.14, and 417.50 ± 44.13 fmol/mL) and non-invasiveness (386.00 ± 49.64, 417.50 ± 44.03, and 409.51 ± 35.17 fmol/mL) (P > 0.05). In patients with pituitary large adeno-mas, the sEGFR levels in pituitary apoplexy (377.48 ± 39.18 fmol/mL) was higher than that in non-pituitary apoplexy (343.18 ± 68.17 fmol/mL, P > 0.05). Conclusions The increased level of peripheral serum sEGFR is concomitant with development, proliferous size of the adenomas in patients with pituitary adenomas. In addition, the elevated levels of serum sEGFR occur in pituitary apoplexy as clinical active tumors, and the non-invasive ACTH secreting adenomas. The sEGFR levels could be differen-tiated helpfully between pituitary adenomas and non-pituitary adenomas. These data suggest that serum sEGFR could be as a referable marker of the size and activation of proliferation in pituitary adenoma.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
To study the role of Ca2+ in the pathogenesis of pituitary growth hormone secreting adenomas, the function of Ca2+ in 23 cases of human Prturtary GH-secreting adenoma was investigated in monolayer cell culture. It wa...To study the role of Ca2+ in the pathogenesis of pituitary growth hormone secreting adenomas, the function of Ca2+ in 23 cases of human Prturtary GH-secreting adenoma was investigated in monolayer cell culture. It was found that Ca2+ channel blockers nicardipin and nifedipin inhibrted basal and growth hormone releasing hormone (GRH)stimulated GH secretion in 87. 5 % and 100. 0 % of the GH adenomas . respectively, demonstrating that in most human pituitary GH adenomas, the basal and GRH regulated GH secretion is Ca2+ dependent. The GRH and sometostatin (SRIF) agonist octreotide regulated the processes of GH secretion via Ca2+ had defects in different steps including receptor ,postreceptor Ca2+ channel and Ca2+GH secreting coupling in 6 (66. 6%) and 5 (55. 5 % ) cases of 9 GH adenomas respectively. Among them,the defects in GRH receptor and SRIF regulated Ca2+ channel are the main causes of the dysfunction of GH adenomas. These defects may be related to GH hypersecretion in GH adenomas. Our data provides advance evidences for intrinsic defects of GH adenomas.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 remova...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 GHPA was much higher than that ofnon-invasive GHPA. The overexpression of EGFL7 was positively correlated with activation of EGFR （p-EGFR）. Noticeably, EGFL7 knockdown sig- nificantly 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 GTI-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
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
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.
文摘AIM: To investigate the influencing factors of visual field improvement after trans-sphenoidal resection of pituitary macroadenomas. METHODS: This retrospective cohort study included 201 patients (366 eyes) with visual field defect induced by pituitary macroadenomas. All of them were treated with trans-sphenoidal surgery. Ophthalmologic evaluation, best -corrected visual acuity (BCVA), and visual field examination were performed before and 3mo after surgery. BCVA, visual field defect index mean deviation (MD), duration of symptoms, age, sex, and volume of tumors were compared. Expression of vascular endothelial growth factor (VEGF) and Ki-67 of tumor tissue were detected by immunohistochemical technique. RESULTS: The mean age of patients was 44.23 +/- 1.29y. Ninety -three patients were female and 108 were male. The mean tumor volume was 14.36 +/- 6.23 cm(3). The mean duration of preoperative symptoms was 11.50 +/- 0.88mo. Mean preoperative MD was -17.50 +/- 0.82 dB. Mean Preoperative visual acuity was 0.64 +/- 0.04. Postoperative visual field improved in 270 (73.77%) eyes, unchanged in 96 (26.23%) eyes. Multivariate logistic regression displayed that the factors independently influencing visual field improvement were young age (OR=1.71, 95%CI: 1.325-2.387, P=0.013), low preoperative MD absolute value (OR=1.277, 95%CI: 1.205-1.355, P<0.001), small volume of tumor (OR=1.458, 95%CI: 1.060-4.289, P<0.001), low expression of VEGF in tumor tissue (OR=1.554, 95%CI: 1.089-2.457, P=0.022), and low expression of Ki-67 in tumor tissue (OR=1.552, 95%CI: 1.161-2.847, P=0.026). CONCLUSION: After pituitary macroadenomas trans sphenoidal resection, the independent influencing factors of the visual fields recovery were low preoperative MD absolute value, young age, small volume of tumor, and expression levels of VEGF/Ki-67.
文摘To investigate effect of the soluble epidermal growth factor receptor (sEGFR/sErbB1) level in the periph-eral blood in development, invasiveness, apoplexy of each type of pituitary tumor. Methods The sEGFR level was determined in peripheral serum from 190 patients with pituitary diseases by enzyme linked immunosobent assay. The sEGFR levels were measured in 10 pituitary Rathke’s pouch, 18 pituitary hyperplasia, 161 pituitary adenomas including 30 microadenomas, 83 large adenomas, 48 giant adenomas, 1 pituitary carcinoma, and 28 hea-lthy controls. Results In the patients with pituitary hyperplasia, microadenoma, large adenoma, giant adenoma, and pituitary carci-noma, the sEGFR level was 188.92 ± 32.62, 209.83 ± 19.01, 333.20 ± 69.33, 405.85 ± 37.38, and 617.45 fmol/mL indepen-dently. They were all significantly higher than patients with pituitary Rathke’s pouch (156.78 ± 18.24 fmol/mL, P < 0.001) and healthy control group (159.11 ± 40.50 fmol/mL, P < 0.05). The sEGFR level in pituitary carcinoma was higher than pi-tuitary adenoma. In patients with pituitary adenoma, the sEGFR level was positive correlated to the size of pituitary adeno-mas (r = 0.998), the significant difference was observed for the sEGFR level in each group of the patients with pituitary adenomas (P < 0.001). Furthermore, in patients with pituitary ACTH-secreting microadenomas, the serum sEGFR levels in invasiveness (295.00 ± 77.80 fmol/mL) was higher than that in non-invasiveness (210.60 ± 16.4 fmol/mL, P < 0.05). In pati-ents with pituitary ACTH-secreting, PRL-secreting, GH-secreting, and non-functioning large adenomas, the serum sEGFR levels in invasiveness (407.86 ± 28.50, 399.25 ± 30.10, 386.00 ± 13.08, and 369.25 ± 36.70 fmol/mL) was higher than that in non-invasiveness (335.25 ± 63.49, 300.64 ± 47.57, 297.00 ± 61.93, and 269.30 ± 25.68 fmol/mL) respectively (P < 0.05). In patients with invasive pituitary PRL-secreting, GH-secreting, and non-functioning giant adenomas, the serum sEGFR levels not significantly different in between invasiveness (417.50 ± 35.94, 409.50 ± 69.14, and 417.50 ± 44.13 fmol/mL) and non-invasiveness (386.00 ± 49.64, 417.50 ± 44.03, and 409.51 ± 35.17 fmol/mL) (P > 0.05). In patients with pituitary large adeno-mas, the sEGFR levels in pituitary apoplexy (377.48 ± 39.18 fmol/mL) was higher than that in non-pituitary apoplexy (343.18 ± 68.17 fmol/mL, P > 0.05). Conclusions The increased level of peripheral serum sEGFR is concomitant with development, proliferous size of the adenomas in patients with pituitary adenomas. In addition, the elevated levels of serum sEGFR occur in pituitary apoplexy as clinical active tumors, and the non-invasive ACTH secreting adenomas. The sEGFR levels could be differen-tiated helpfully between pituitary adenomas and non-pituitary adenomas. These data suggest that serum sEGFR could be as a referable marker of the size and activation of proliferation in pituitary adenoma.
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
文摘To study the role of Ca2+ in the pathogenesis of pituitary growth hormone secreting adenomas, the function of Ca2+ in 23 cases of human Prturtary GH-secreting adenoma was investigated in monolayer cell culture. It was found that Ca2+ channel blockers nicardipin and nifedipin inhibrted basal and growth hormone releasing hormone (GRH)stimulated GH secretion in 87. 5 % and 100. 0 % of the GH adenomas . respectively, demonstrating that in most human pituitary GH adenomas, the basal and GRH regulated GH secretion is Ca2+ dependent. The GRH and sometostatin (SRIF) agonist octreotide regulated the processes of GH secretion via Ca2+ had defects in different steps including receptor ,postreceptor Ca2+ channel and Ca2+GH secreting coupling in 6 (66. 6%) and 5 (55. 5 % ) cases of 9 GH adenomas respectively. Among them,the defects in GRH receptor and SRIF regulated Ca2+ channel are the main causes of the dysfunction of GH adenomas. These defects may be related to GH hypersecretion in GH adenomas. Our data provides advance evidences for intrinsic defects of GH adenomas.
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 GHPA was much higher than that ofnon-invasive GHPA. The overexpression of EGFL7 was positively correlated with activation of EGFR （p-EGFR）. Noticeably, EGFL7 knockdown sig- nificantly 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 GTI-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.
