Objective To detect the effects of 17 β-estradiol(E2)on the expression of Calbindin-D9k (CaBP-9k) in pituitary GH3 cells,and to investigate the antagonistic effect of a selective estrogen receptor antagonist,ⅡCI 182780 on CaBP-9k expression.Methods A rat pituitary prolactinoma cell line,GH3 cell was used as the in vitro model.The localization of CaBP-9k in GH3 cells was observed by immunofluorescence.GH3 cells were cultured with exogenous E2-added medium for 24 hours,and the concentrations of E2 were 10-8,10-9,10-10M,respectively.mRNA and protein expression levels of CaBP-9k in different groups were analyzed by RT-PCR and Western blot analysis.The estrogen receptor antagonist,and ⅡCI 182780 was added to GH3 cells before E2 administration (10-8M)with the concentration of 10-6M,in order to investigate the regulation of ER-mediated pathway on the expression of CaBP-9k.Immunoprecipitation was used to detect the interaction between CaBP-9k and ERα.Results E2 had significant stimulatory effect on the CaBP-9k expression of GH3 cells in a dose dependent manner,and the expression level of CaBP-9k was higher when treated with a higher concentration of E2.ⅡCI 182780 could suppress the stimulatory effect of E2 on the CaBP-9k expression of GH3 cells.The expression level of CaBP-9k was significantly reduced by coadministration of E2 with ⅡCI 182780 in GH3 cells,which meant the CaBP-9k expression was mediated through ERα pathway.The immunoprecipitation results further illustrated the fact that CaBP-9k could directly interact with ERα,and E2 could increase the interaction between CaBP-9k and ERα.Conclusion Estrogen might induce CaBP-9k expression via ERα mediated pathway and CaBP-9k could directly combine with ERα,suggesting that CaBP-9k might be involved in the biological effects mediated by ER pathway in GH3 cells.

Objective To investigate the relationship between tumor invasion and changes of mRNA expression of MMP-2, TIMP-2 and CD147 in human pituitary adenoma. Methods 60 patients with pituitary adenoma were devided into two groups, invasive and non-invasive group, by MRI. The expression level of MMP-2,TIMP-2 and CD147 in the samples of pituitary adenoma was measured by semiquantitative reverse transcriptasepolymerase chain reaction (RT-PCR). Pearson analysis was used to reveal the correlation between the expression of each marker. Results The mRNA expression level of MMP-2 and CD147 was significantly higher in invasive pituitary adenoma group than that in non-invasive group (P ＜ 0. 01 ) while the mRNA expression level of TIMP-2was lower in invasive pituitary adenoma group than that in non-invasive group (P ＜0.01 ). According to Pearson analysis, the mRNA expression of MMP-2 was positively correlated with CD147 in invasive pituitary adenoma (r=0. 69, P ＜ 0. 05 ), and M MP-2 was negatively correlated with TIMP-2 in non-invasive pituitary adenoma (r =-0.68, P ＜ 0.05 ). Conclusions The invasion of human pituitary adenoma are closely related to the low expression level of TIMP-2 as well as the high expression level of MMP-2 and CD147. MMP-2, TIMP-2 and CD147 can be used as indicators of tumor invasion of human pituitary adenoma.

Hypopituitorism is a common complication of traumatic brain injury (TBI),which can happen both at acute and chronic stages after TBI.There are different clinical features of hypopituitorism happened at acute and chronic stages.At acute stage,dysfunction of pituitary-adrenal cortical axis is of the most clinical significance,which can cause hypotension,hypoglycemia,hyponatremia and lead to life-threatening complications.Growth hormone deficiency and hypogonadotropic hypogonadism are the two most common endocrine deficits at chronic stage.Symptoms of hypopituitorism at chronic stage include fatigue,cognitive impairment,decreased exercise capacity,decreased libido and so on.Assessment of pituitary function should be carried out for patients with moderate to severe TBI during the acute phase,focusing on the function of pituitary-adrenal axis.If patients manifest symptoms related to hypopituitorism during chronic stage,comprehensive evaluation of pituitary function should be carried out.The diagnosis of hypopituitorism should be based on basic hormone level and corresponding stimulation test.Hypofunction of pituitary-adrenal cortical axis in the acute phase of TBI should be treated with glucocorticoid immediately because of its potential contribution to the acute morbidity and mortality.Severe hypofunction of pituitary-thyroid axis should also be treated with thyroxine replacement.Most growth hormone deficiency and hypofunction of pituitary-gonadal axis occurred in the acute phase could be improved by themselves with time migration,so there is no need to be treated in this phase.Hypopituitorism occurred in the chronic phase of TBI may have lasting effect on cognition and life quality.Hormone replacement should be carried out once the diagnosis is confirmed.

Objective:To explore the clinical features, diagnosis and treatment of hypopituitorism after severe traumatic brain injury (TBI) in acute phase.Methods:Twenty-four patients with hypopituitorism after severe TBI that were diagnosed and treated in China-Japan Union Hospital from Jan. 2017 to Sep. 2018 were retrospectively analyzed.Results:Pituitary function was evaluated between 3 to 7 days after TBI, and hypopituitorism was detected in 15.2% (24/158) of patients with severe TBI. The average age of the 24 patients was 35.8 (range from 18 to 65) years, and the median GCS score on admission was 5.6 (range from 3 to 8) . The pituitary endocrine axis was involved as follows: hypofunction of pituitary-adrenal in 9 cases, hypofunction of pituitary-thyroid axis in 7 cases, hypofunction of pituitary-thyroid axis and pituitary-adrenal axis in 6 cases, hypofunction of growth hormone axis in 1 case and pituitary-gonad axis in 1 case. Hydrocortisone replacement was carried out in patients with hypofunction of pituitary-adrenocortical axis, and patients with hypofunction of pituitary-thyroid axis were given levothyroxine replacement therapy. All patients were followed up at 3 months after injury. Among the patients with pituitary-thyroid axis hypofunction, 61.5% (8/13) returned to normal. The pituitary-adrenocortical axis function returned to normal in 40% (6/15) patients with pituitary-adrenocortical axis hypofunction. Both the function of the growth hormone axis and the pituitary-gonad axis returned to normal.Conclusions:It is not uncommon for severe TBI patients to be complicated with hypopituitorism at early stage, which should be paid enough attention. Assessment of pituitary function at early stage can help to screen out the patients with severe adrenocortical hypofunction and hypothyroidism. Hormone replacement treatment should be carried out as early as possible, which has important significance for improving the prognosis of severe TBI patients.

Hypopituitorism is not uncommon in patients with aneurysmal subarachnoid hemorrhage (aSAH) . It can happen both in acute and chronic stages of aSAH. There are different clinical features of hypopituitorism happened in acute and chronic stages. In the acute stage, pituitary-adrenocortical axis dysfunction is of the most clinically significant, which can cause adrenal crisis. Growth hormone deficiency and pituitary-adrenocortical axis dysfunction are the two most common endocrine deficits in the chronic stage, symptoms include fatigue, decreased exercise capacity, cognitive impairment and decreased libido et al. The mechanism and risk factors of hypopituitorism are still unclear. The function of pituitary-adrenal axis should be paid attention for patients with aSAH during the acute phase. If patients manifest symptoms related to hypopituitorism during the chronic stage, comprehensive evaluation of pituitary function should be carried out. The diagnosis of hypopituitorism should be based on basic hormone level and corresponding stimulation test. Hypocortisolism in the acute phase of aSAH should be treated with glucocorticoid because of its potential contribution to the morbidity and mortality. Hypopituitorism occurred in the chronic phase of aSAH may have lasting effect on cognition and life quality, and hormone replacement should be carried out once the diagnosis be confirmed.

Objective:To explore the risk factors of hypopituitorism after aneurysmal subarachnoid haemorrhage (aSAH) in the acute phase and analysis the effect of hypopituitorism on prognosis.Methods:Patients with aSAH that were diagnosed and treated in China-Japan Union Hospital from Sep. 2017 to Sep. 2018 and undergoing pituitary function evaluation within 3 to 7 days were retrospectively analyzed. 72 patients were enrolled, including 31 males and 41 females. The average age was 50.1 years old (36-71) . The WFNS gradings were Ⅰ, 24; Ⅱ, 20; Ⅲ, 15; Ⅳ, 10; Ⅴ, 3. The Fisher gradings were 2, 21; 3, 38; 4, 13. Acute hydrocephalus happened in 13 cases. Aneurysm located in the Willis circle in 56 cases and not in the Willis circle in 16 cases. 37 cases were treated by microsurgical clipped and 35 cases were treated by embolism. Patients with hypocortisolism were treated by hydrocortisone replacement, and patients with hypothyroidism were given levothyroxine replacement therapy. Patients were followed up at 3 months and their recovery was evaluated by GOS score.Results:Hypopituitorism was detected in 34 patients; the incidence of hypopituitorism was 47.2%. There was no significant correlation between the occurrence of hypopituitorism and age, gender, and hydrocephalus ( P>0.05) . Patients with WFNS grade ≥Ⅳ, Fisher grade 4, aneurysm located in the Willis circle, and treated by clipping were more likely to undergo hypopituitorism. The proportion of patients with good recovery (GOS ≥4) in the hypopituitorism group was smaller than that in the normal pituitary function group at the 3-month follow-up. Conclusions:Patients with WFNS grade ≥Ⅳ, Fisher grade 4, aneurysm located in the Willis circle, and treated by clipping are more likely to undergo hypopituitorism. Hypopituitorism in acute stage affects the prognosis of aSAH patients. Patients with hypocortisolism and hypothyroidism should be treated actively.