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1.
K. Koike Z. X. Zhang Y. Sakamoto A. Miyake M. Inoue 《American journal of reproductive immunology (New York, N.Y. : 1989)》1998,39(3):217-222
PROBLEM: Cytokine-induced neutrophil chemoattractant (CINC) was reported to influence anterior pituitary hormone release. We recently found that Unkei-to, one of the Japanese Kampo medicines, stimulated CINC secretion by rat anterior pituitary cells and the pituitary folliculo-stellate (FS)-like cell line (TtT/GF). Therefore, the effect of Unkei-to on growth hormone (GH) secretion by rat anterior pituitary cells was investigated. METHOD OF STUDY: Dispersed normal anterior pituitary cells, the folliculo-stellate-like cell line TtT/GF, and the GH3 cell were used to test the effect of Unkei-to on GH secretion. In reconstitutive coculture experiments, TtT/GF cells were mixed with GH3 cells at a ratio (TtT/GF cells: GH3 cells) of 1:99. From this mixture, cells were seeded onto plates at a density of 104 cells/well and were cultured for 5 days. The cells were then used in the experiments. RESULTS: Unkei-to at 20 μg/ml significantly inhibited GH secretion by normal anterior ptuitary cells within 12 hr of incubation. In contrast Unkei-to stimulated GH secretion by GH3 cells in a time- and dose-dependent manner, suggesting that an accessory cell type was involved. To assess the contribution of CINC as a paracrine factor, an experiment using a reconstitutive coculture system was performed, and Unkei-to was found to inhibit GH secretion when GH3 cells were cocultured with TtT/GF cells. The addition of anti-CINC antibody to the reconstitutive coculture system antagonized Unkei-to-inhibited GH secretion. CONCLUSION: CINC, which was secreted from FS cells by Unkei-to, may be responsible for mediating the inhibitory effect of Unkei-to on GH secretion by rat anterior pituitary cells. 相似文献
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3.
B W Scheithauer E R Laws K Kovacs E Horvath R V Randall J A Carney 《Seminars in diagnostic pathology》1987,4(3):205-211
In a series of 1,500 pituitary adenomas surgically resected at Mayo Clinic, 41 (2.7%) occurred in the setting of multiple endocrine neoplasia, type I (MEN-I). Of the 40 patients (18 males, 22 females), 21 (52%) presented with clinical evidence of a pituitary neoplasm, 13 with hyperparathyroidism, and two with functional islet cell tumor. Of the 41 tumors, 11 (27%) were microadenomas, and 30 (73%) were macroadenomas. Immunocytochemical studies demonstrated the following reactivities: GH (4), GH/PRL (6), GH/PRL/glycoprotein (7), GH/ACTH/glycoprotein (1), PRL (16), PRL/TSH (1), ACTH (3), and null cell adenoma (3). We conclude that, in comparison with pituitary adenomas occurring in the general population, those occurring in association with MEN-I are (1) more often endocrinologically functional, (2) more frequently GH- or PRL-producing, and (3) clinicopathologically similar in terms of the subjects age and sex as well as of tumor size and invasiveness. 相似文献
4.
DNA Methylation Regulates p27Kip1 Expression in Rodent Pituitary Cell Lines 总被引:11,自引:0,他引:11
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Xiang Qian Long Jin Elzbieta Kulig Ricardo V. Lloyd 《The American journal of pathology》1998,153(5):1475-1482
We previously reported loss of expression of p27Kip1 (p27) protein in rat GH3 and mouse GHRH-CL1 pituitary tumor cells compared with normal pituitary (NP). The molecular basis for the loss of expression of p27 protein in GH3 and GHRH-CL1 cells is unknown. To determine the role of p27 gene methylation in the regulation of the expression of this cell cycle protein, the methylation patterns of p27 in normal and neoplastic pituitary cells was analyzed. Inhibition of DNA methyltransferase (DNA-MTase) with 5-aza-2′-deoxycytidine (AZAdC) induced expression of both p27 protein and mRNA when GH3 and GHRH-CL1 cells were treated for 7 days in vitro. DNA methylation correlated inversely with the expression of p27 gene products in NP and pituitary tumor cell lines. Bisulfite genomic sequencing analysis showed that the normally unmethylated cytosines in exon 1 in NP and AtT20 cells were extensively methylated in GH3 and GHRH-CL1 cells. After treatment of GH3 and GHRH-CL1 cells with 10 μmol/L AZAdC, there were decreased numbers of methylated cytosines (by 60% to 90%) with variable methylation patterns observed by bisulfite genomic sequencing. Analysis of genomic DNA with methylation-sensitive enzymes showed that all SmaI, HhaI, and AvaI enzyme sites of the p27 gene in exon 1 were methylated in GH3 cells but not in NP, confirming the bisulfite genomic sequencing results. AtT20 cells and a human pituitary null cell adenoma cell line (HP75), which expressed abundant p27, had a methylation pattern similar to the NP. DNA-MTase activity was elevated fourfold in GH3 cells and twofold in GHRH-CL1 cells compared with DNA-MTase activity in NP and AtT20 cells. These results suggest that increased DNA methylation is another mechanism of silencing of the p27 gene in some pituitary tumors and possibly in other types of neoplasms. 相似文献
5.
C.B. Murat P.B.S. Braga M.A.H.Z. Fortes M.D. Bronstein M.L.C. Corrêa-Giannella R.R. Giorgi 《Brazilian journal of medical and biological research》2012,45(9):851-855
The tumorigenesis of pituitary adenomas is poorly understood. Mutations of the PIK3CA proto-oncogene, which encodes the p110-α catalytic subunit of PI3K, have been reported in various types of human cancers regarding the role of the gene in cell proliferation and survival through activation of the PI3K/Akt signaling pathway. Only one Chinese study described somatic mutations and amplification of the PIK3CA gene in a large series of pituitary adenomas. The aim of the present study was to determine genetic alterations of PIK3CA in a second series that consisted of 33 pituitary adenomas of different subtypes diagnosed by immunohistochemistry: 6 adrenocorticotropic hormone-secreting microadenomas, 5 growth hormone-secreting macroadenomas, 7 prolactin-secreting macroadenomas, and 15 nonfunctioning macroadenomas. Direct sequencing of exons 9 and 20 assessed by qPCR was employed to investigate the presence of mutations and genomic amplification defined as a copy number ≥4. Previously identified PIK3CA mutations (exon 20) were detected in four cases (12.1%). Interestingly, the Chinese study reported mutations only in invasive tumors, while we found a PIK3CA mutation in one noninvasive corticotroph microadenoma. PIK3CA amplification was observed in 21.2% (7/33) of the cases. This study demonstrates the presence of somatic mutations and amplifications of the PIK3CA gene in a second series of pituitary adenomas, corroborating the previously described involvement of the PI3K/Akt signaling pathway in the tumorigenic process of this gland. 相似文献
6.
Pituitary hyperplasia and tumor growth are regulated by various hormones and growth factors. Estrogen (E2) stimulates pituitary cell proliferation and prolactin (PRL) production. Estrogen also regulates transforming growth factor-β
(TGF-β) effects in the pituitary. TGF-β in turn regulates various cell cycle proteins including p15 and p27Kip1 (p27). To better understand the regulatory role of growth factors and hormones in the cell cycle we analyzed cyclin D1, cyclin E, and p27 expression in normal and neoplastic rat pituitary cells. An in vitro analysis using cultured normal pituitary
cells and GH3 tumor cells and an in vivo analysis of estrogen-treated normal pituitary and implanted GH3 cells were performed. Semiquantitative RT-PCR was used to analyze mRNA expression for cyclin D1, cyclin E, and p27 in cultured pituitary cells and E2-treated pituitaries in vivo. Cyclin D1 and p27 were localized in the nuclei of normal pituitary cells by immunocytochemistry (ICC). Very weak or absent immunostaining
for cyclin D1 and p27 was present in GH3 cells. Both normal pituitary and GH3 cells had strong nuclear staining for cyclin E. Normal pituitary had a 20-fold greater amount of cyclin D1 mRNA and a 3-fold greater amount of p27 mRNA compared to GH3 cells, whereas GH3 cells had slightly (1.5-fold) more cyclin E than normal pituitary cells. E2 treatment in vivo stimulated cell proliferation and decreased cyclin D1 mRNA levels in normal pituitary. GH3 tumor cells, implanted subcutaneously in the same animal, showed increased proliferation after E2 treatment, but there was no change in cyclin D1 mRNA in GH3 cells. Cyclin E and p27 mRNA levels did not change significantly in normal pituitary or in GH3 cells after E2 treatment in vivo. Treatment of normal pituitary cells with 10−9
M TGF-β1 for 3 d in vitro led to significant decreases in cyclin D1 and p27 mRNAs (p < 0.05), whereas cyclin E levels were unchanged. These results indicate that cyclin D1 and p27 mRNAs are present at significantly higher levels in normal pituitary compared to GH3 cells, and that both E2 and TGF-β1 can downregulate cyclin D1 mRNA levels in normal pituitary cells, suggesting that these factors regulate G1 to S phase transition in pituitary cells.
The lower levels of specific cell cycle regulators in GH3 cells may explain the decreased regulatory control by E2 in GH3 tumor cells. 相似文献
7.
Ewa Jasek Alicja Furgal-Borzych Grzegorz J. Lis Jan A. Litwin Ewa Rzepecka-Wozniak Franciszek Trela 《Endocrine pathology》2009,20(4):221-226
Microvessel density (MVD) and area (MVA) were assessed in 53 clinically silent pituitary microadenomas and in surrounding
normal pituitary tissue using CD34 immunostaining and digital image analysis system. Twenty-one microadenomas (40%) were avascular;
in the others, both MVD and MVA were significantly lower than in the normal pituitary tissue. No significant differences in
MVD and MVA were found between hormonally immunonegative and immunopositive tumors or between different hormonal subtypes
of immunopositive microadenomas. In microadenomas and in normal pituitary tissue, MVD and MVA were not significantly influenced
by age or sex. These results suggest that pituitary adenomas at early developmental stage are either avascular or significantly
less vascular than normal pituitary tissue and that differences in vascularity of pituitary adenomas associated with the variables
of sex, age, clinical presentation and immunohistochemical phenotype reported in the literature can evolve with tumor growth
and possibly acquire statistical significance in large macroadenomas. 相似文献
8.
Han Hyuk Lim Yoo Mi Kim Gyung Min Lee Jaehong Yu Heon-Seok Han Jeesuk Yu 《Journal of Korean medical science》2022,37(11)
BackgroundThe study aimed to compare the growth responses to 3 years of growth hormone (GH) treatment in children and adolescents with GH deficiency (GHD) according to idiopathic, organic, isolated (IGHD), and multiple pituitary hormone deficiency (MPHD).MethodsTotal 163 patients aged 2–18 years (100 males and 63 females; 131 idiopathic and 32 organic GHD; 129 IGHD and 34 MPHD) were included from data obtained from the LG Growth Study. Parameters of growth responses and biochemical results were compared during the 3-year GH treatment.ResultsThe baseline age, bone age (BA), height (Ht) standard deviation score (SDS), weight SDS, mid-parental Ht SDS, predicted adult Ht (PAH) SDS, and insulin like growth factor-1 (IGF-1) SDS were significantly higher in the organic GHD patients than in the idiopathic GHD patients, but peak GH on the GH-stimulation test, baseline GH dose, and mean 3-year-GH dosage were higher in the idiopathic GHD patients than in the organic GHD patients. The prevalence of MPHD was higher in the organic GHD patients than in the idiopathic GHD patients. Idiopathic MPHD subgroup showed the largest increase for the ΔHt SDS and ΔPAH SDS during GH treatment, and organic MPHD subgroup had the smallest mean increase after GH treatment, depending on ΔIGF-1 SDS and ΔIGF binding protein-3 (IGFBP-3) SDS. The growth velocity and the parental-adjusted Ht gain were greater in the idiopathic GHD patients than the organic GHD patients during the 3-year GH treatment, which may have been related to the different GH dose, ΔIGF-1 SDS, and ΔIGFBP-3 SDS between two groups. Multiple linear regression analysis revealed that baseline IGF-1 SDS, BA, and MPH SDS in idiopathic group and baseline HT SDS in organic group are the most predictable parameters for favorable 3-year-GH treatment.ConclusionThe 3-year-GH treatment was effective in both idiopathic and organic GHD patients regardless of the presence of MPHD or underlying causes, but their growth outcomes were not constant with each other. Close monitoring along with appropriate dosage of GH and annual growth responses, not specific at baseline, are more important in children and adolescents with GHD for long-term treatment.Trial RegistrationClinicalTrials.gov Identifier: NCT01604395相似文献
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10.
Benoit H Busso T Castells J Geyssant A Denis C 《European journal of applied physiology》2003,90(5-6):514-519
The aim of this study was to evaluate the influence of arterial oxygen saturation (SaO2) on maximal heart rate during maximal exercise under conditions of acute hypoxia compared with normoxia. Forty-six males were divided into three groups depending on their sea level maximal oxygen consumption (O2max): high [GH, O2max=64.2 (3.3) ml.min–1.kg–1], medium [GM, 50.8 (3.9) ml.min–1.kg–1] and low [GL, 41.0 (1.9) ml.min–1.kg–1]. All subjects performed a maximal exercise test in two conditions of inspired oxygen tension (PIO2, (149 mmHg and 70 mmHg). Among the GM group, seven subjects performed five supplementary incremental exercise tests at PIO2 136, 118, 104, 92, and 80 mmHg. Measurements of O2max and SaO2 using an ear-oxymeter were carried out at all levels of PIO2. The decrease in SaO2 and peak heart rate (HRpeak) with PIO2 became significant from 104 and 92 mmHg. SaO2 correlated with the decrease in HRpeak. For PIO2=70 mmHg, the decrease in O2max, SaO2 and HRpeak was, respectively, 44%, 62%, and 17.0 bpm for GH, 38%, 68%, and 14.7 bpm for GM, and 34%, 68%, and 11.8 bpm for GL. During maximal exercise in hypoxia, SaO2 was lower for GH than GM and GL (p<0.01). Among subjects in GH, five presented exercise-induced hypoxemia (EIH) when exercising in normoxia. The EIH group exhibited a greater decrement in HRpeak than the non-EIH group at maximal hypoxic exercise (21.2 bpm vs. 15.0 bpm; p<0.05). When subjects are exposed to acute hypoxia, the lower SaO2, due either to lower PIO2 or to training status, is associated with lower HRpeak. 相似文献
11.
Elaine Lu Wang Zhi Rong Qian Md Mustafizur Rahman Katsuhiko Yoshimoto Shozo Yamada Eiji Kudo Toshiaki Sano 《Histopathology》2010,56(4):501-509
Wang E L, Qian Z R, Rahman M M, Yoshimoto K, Yamada S, Kudo E & Sano T (2010) Histopathology 56, 501–509 Increased expression of HMGA1 correlates with tumour invasiveness and proliferation in human pituitary adenomas Aims: High‐mobility group A1 (HMGA1) is highly expressed in various benign and malignant tumours. The development of pituitary adenoma in Hmga1 transgenic mice has been reported. However, no studies have investigated HMGA1 expression and its clinical significance in human pituitary adenomas. Methods and results: Immunohistochemical expression of HMGA1 was analysed with respect to various clinicopathological factors in 95 pituitary adenomas. Nuclear expression of HMGA1 was observed in 62% of pituitary adenomas, whereas normal adenohypophysial tissues were negative. Although HMGA1 expression was frequently detected in clinically non‐functioning adenomas – 90% of silent adrenocorticotropic hormone (ACTH), 76.2% of follicle‐stimulating hormone/luteinizing hormone and 100% of null cell adenomas – it was also detected in 48.1% of growth hormone (GH), 60% of mixed GH/prolactin (PRL), 62.5% of PRL, 66.6% of thyroid‐stimulating hormone and 37.5% of ACTH adenomas. HMGA1 expression was significantly higher in invasive adenomas or macroadenomas than in non‐invasive adenomas or microadenomas (invasive versus non‐invasive, P < 0.05; macroadenoma versus microadenoma, P < 0.05). In addition, HMGA1 showed the highest level in grade IV, more aggressive pituitary adenomas, than in grades I, II and III (IV versus I, P = 0.01; IV versus II, P = 0.01; IV versus III, P = 0.07). Furthermore, a significant correlation between HMGA1 expression and MIB‐1 labelling index was observed (R = 0.368, P < 0.0002). Conclusions: These findings suggest that HMGA1 up‐regulation has an important oncogenic role in pituitary tumorigenesis, as well as being a novel molecular marker of tumour proliferation and invasiveness. 相似文献
12.
Takanori Ebisawa Katsuyoshi Tojo Naoko Tajima Masami Kamio Yutaka Oki Katsuhiko Ono Hironobu Sasano 《Endocrine pathology》2008,19(4):252-260
Subclinical Cushing’s disease (SCD) is characterized by lack of clinically evident Cushingoid features, despite abnormal hypersecretion
of ACTH. Nearly half the cases of SCD are due to macroadenomas, and in the majority of them, ACTH secretion is not inhibited
even by high-dose dexamethasone. Impaired glucocorticoid (GC) action may be correlated with the proliferation and development
of pituitary macroadenomas causing SCD. In this study, immunohistochemical analysis of the resected tumors were performed
to evaluate the expression of 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) and glucocorticoid receptor (GR) in pituitary
tissues obtained from two SCD (macroadenomas), eight Cushing’s disease (CD) (microadenomas), nine acromegaly, and nine normal
pituitary (NP). Scattered 11βHSD2-immunopositive cells were detected in all NP tissues, but its immunoreactivity was totally
absent in any tumorous tissues except two CD. Scattered GR-immunopositive cells were also detected and GR immunostaining was
restricted to the cytosol in NP tissue. In contrast, GR-immunopositive cells were abundantly present and GR immunostaining
was restricted to the nucleus in all the tumorous tissues. There were marked differences in both expression levels and localization
between NP tissues and all the tumors. There may be a mechanism other than that via 11βHSD2 for causes of impaired negative
feedback action by GC in SCD and CD, but results of our present study suggest that impaired GC action may be involved, at
least in part, in tumorigenesis of SCD and CD. 相似文献
13.
We previously reported that increased DNA methylation was an important mechanism of silencing the p27 gene in some pituitary
tumor cell lines [1]. DNA methylation correlated inversely with p27 gene expression. The p27 and cyclin D2 genes are located
in the same region of mouse chromosome 6, rat chromosome 4, and human chromosome 12p13. Because both genes are located in
the same gene cluster, we investigated whether methylation was a principal mechanism regulating cyclin D2 as well as p27 expression
in rodent pituitary cell lines. Bisulfite genomic sequencing showed that the normally unmethylated cytosines of the p27 gene
in normal pituitary (NP) were extensively methylated in GH3 and GHRH-CL1 cells, but not in AtT 20, αT3-1 and LβT2 cells; but cyclin D2 was extensively inactivated in various pituitary tumor cell lines by increased DNA methylation. These abnormalities of methylation in p27 and cyclin
D2 genes occurred with different frequencies in five pituitary tumor cell lines with 100% (5/5) methylation of the cyclin
D2 gene and 40% (2/5) methylation of the p27 gene. Treatment with the methyl transferase inhibitor 5′-aza-2′-deoxycytidine
(AZAdC) increased expression of cyclin D2 and p27 in GH3 and GHRH-CL1 pituitary tumor cells. There was a correlation between
hypermethylation and gene expression. GH3 tumors implanted into Wistar-Furth rats in vivo did not change the methylation status of the p27 and cyclin D2 genes. These
data indicate a coordinately reduced expression of these two linked genes in most rodent pituitary tumor cell lines and suggest
that methylation of cyclin D2 and p27 might occur in a “hot spot” in this gene-rich cluster.
Supported in part by NIH CA 37231 and CA 42951 相似文献
14.
In-Jung Jun Mi Hwa Chung Jung Eun Kim Hye Sun Lee Jung Mo Son Eun Mi Choi 《International journal of medical sciences》2021,18(12):2589
Background: Dynamic preload parameters such as pulse pressure variation (PPV) and stroke volume variation (SVV) have widely been used as accurate predictors for fluid responsiveness in patients under mechanical ventilation. To circumvent the limitation of decreased cyclic change of intrathoracic pressure, we performed an intermittent PEEP challenge test to evaluate whether PPV or SVV can predict fluid responsiveness during one-lung ventilation (OLV).Methods: Forty patients undergoing OLV were analyzed. Baseline hemodynamic variables including PPV and SVV and respiratory variables were recorded after chest opening in lateral position under OLV (T1). Five minutes after application of PEEP 10 cmH2O, the parameters were recorded (T2). Thereafter, PEEP was withdrawn to 0 cmH2O for 5 minutes (T3), and fluid loading was performed with balanced crystalloid solution 6 mL/kg of ideal body weight for 5 minutes. Five minutes after completion of fluid loading, all variables were recorded (T4). The patient was classified as fluid responder if SV increased ≥10% after fluid loading and as non-responder if SV increased <10%.Results: Prediction of fluid responsiveness was evaluated with area under the receiver operating characteristic (ROC) curve (AUC). Change in stroke volume variation (ΔSVV) showed AUC of 0.9 (P < 0.001), 95% CI = 0.82-0.99, sensitivity = 88%, specificity = 82% for discrimination of fluid responsiveness. Change in pulse pressure variation (ΔPPV) showed AUC of 0.88 (P < 0.001), 95% CI = 0.78-0.97, sensitivity = 83%, specificity = 72% in predictability of fluid responsiveness. Cardiac index and stroke volume were well maintained after PEEP challenge in non-responders while they increased in responders.Conclusions: ΔPPV and ΔSVV induced by PEEP challenge are reliable parameters to predict fluid responsiveness as well as very good predictors of fluid unresponsiveness during OLV. 相似文献
15.
The effects of estradiol 17β (E2) on the regulation of estrogen receptor (ER) mRNA amounts in normal and neoplastic rat pituitary tissues were analyzed by
in situ hybridization with an oligonucleotide probe. E2 treatment produced a significant increase in ER mRNA amounts in two transplantable pituitary tumors (MtT/Wl5 and MtT/F4)
and in the GH3 cell line. ER mRNA amounts were also increased In normal pituitaries after 6 weeks of E2 treatment, but the differences were not significant. Biochemical assay of ER proteins confirmed the presence of ER protein
in MtT/Wl 5 and MtT/F4 tumors. “Cytoplasmic” ER proteins were decreased by E2 in the MtT/Wl5 tumor.These results indicate that ER mRNA is present in normal pituitaries and in pituitary tumors and can
be regulated by estrogen treatment in vivo and in vitro. The inhibitory effects of high estrogen concentration on proliferation
of transplantable pituitary tumors in vivo and GH3 cells in vitro is not explained by the absence of ER mRNAs in these tumors. 相似文献
16.
Determination of the proliferation and apoptotic index in adrenocorticotropin-secreting pituitary tumors : comparison between micro- and macroadenomas 总被引:3,自引:0,他引:3
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Losa M Barzaghi RL Mortini P Franzin A Mangili F Terreni MR Giovanelli M 《The American journal of pathology》2000,156(1):245-251
We investigated the growth fraction and cell loss fraction in a large group of patients with Cushing's disease subdivided according to tumor size. Fifty-one patients, 8 males and 43 females, aged 12 through 61 years (mean age 34.6 +/- 1.5 years), were studied. Thirty-six patients had a microadenoma and the remaining 15 a macroadenoma. Immunohistochemical analysis was performed on paraffin-embedded material using a monoclonal antibody (MIB-1) directed against a proliferation-associated nuclear antigen, Ki-67, to measure the growth fraction. Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method, using a monoclonal antibody recognizing areas of DNA fragmentation. Ki-67 labeling index and apoptosis were counted on separate slides in at least 1000 evaluable cells. Patients with a macroadenoma had a significantly higher value of Ki-67 index (9.3 +/- 2.7%) than patients with microadenoma (2.8 +/- 0.5%; P < 0.002), whereas the apoptotic index was not significantly different in the two groups (1.7 +/- 0.8% in macroadenomas versus 0.8 +/- 0.3% in microadenomas). Our study shows that ACTH-secreting macroadenomas are characterized by a higher cell growth fraction than microadenomas, whereas the cell loss fraction is not different. A high proliferation rate seems to play a major role in determining the progression from small to large pituitary tumors in Cushing's disease. 相似文献
17.
Scheithauer BW Kovacs KT Stefaneanu L Horvath E Kane LA Young WF Lloyd RV Randall RV Davis DH 《Endocrine pathology》1995,6(3):173-187
To compare the pituitary pathology of gigantism to that of acromegaly, 19 surgically resected lesions were studied from 10
males and 9 females, ages 13–49 (mean, 19 yr) with excessive height (≥95th percentile), onset of disease prior to puberty,
elevated growth hormone (GH) levels despite glucose suppression, and a pathologically confirmed GH-producing pituitary mass.
One patient had MEN-I. The lesions included 18 adenomas and 1 case of pure hyperplasia. The median, mean, and range of serum
GH and prolactin (PRL) levels were 64, 235, 5–1000 ng/mL and 47, 146, 29–770 ng/mL, respectively. Of the 8 adenoma specimens
accompanied by nontumoral pituitary (i.e., tissue wherein the presence of hyperplasia was assessable), 3 (37%) demonstrated
both. Of the 18 tumors, 78% were macroadenomas and 22% were grossly invasive; their immunophenotypes included GH (5%), GH
and PRL (19%), and GH-PRL and a glycoprotein hormone, usually TSH and/or α-subunit (76%). Of the 10 adenoma-containing lesions
subject to electron microscopy (EM), 2 consisted of GH cells alone; 2 of mammosomatotroph (MS) cells alone; 1 of GH and MS
cells; 1 of GH and PRL cells; 2 of GH, PRL, and MS cells; 1 of GH, PRL, and glycoprotein cells; and 1 was a subtype 3 adenoma.
Ultrastructurally, GH cells and/or MS cells predominated in these lesions. Immuno-EM of one GH and PRL cell and of one GH-PRL-MS
tumor showed GH and PRL to be present not only in single cells but within the same granules. Nine of 12 adenoma-associated
lesions subject to combinedin situ hybridization (ISH) and immunostaining showed double labeling for PRL (or GH) mRNA and for GH (or PRL), respectively, features
indicating MS differentiation. In the 4 lesions exhibiting hyperplasia, either alone (1) or in association with adenoma (3),
EM showed MS cells in 3, and immuno-EM as well as combined immunohistochemistry and ISH showed double labeling for GH and
PRL in both of the 2 cases studied. In summary, although in terms of their tinctorial characteristics and tumor size, the
lesions of giants resemble those of acromegalics, those of the former are less often invasive and glycoprotein hormone containing,
and more often contain ultrastructurally distinctive MS cells. The high frequency of adenoma with hyperplasia (37%) and the
occurrence of hyperplasia alone (6%) is of particular notice since this finding is rare in patients with acromegaly. Hyperplasia
is, however, seen in ectopic GH-releasing hormone production and the McCune-Albright syndrome. We conclude that the presence
of MS is not rare in the pituitary lesions of patients with gigantism. Their presence may be a reflection of either hypothalamic
dysfunction or of an intrinsic abnormality of pituitary cells. 相似文献
18.
Luis?Carretero Francisco?Barros Pablo?Miranda Jorge?Fernández-Trillo Angeles?Machín Pilar?de la?Pe?a Pedro?Domínguez
While the thyrotropin-releasing hormone (TRH) effect of raising intracellular Ca2+ levels has been shown to rely on Gq/11 and PLC activation, the molecular mechanisms involved in the regulation of ERG K+ channels by TRH are still partially unknown. We have analysed the effects of βγ scavengers, Akt/PKB inactivation, and TRH
receptor (TRH-R) overexpression on such regulation in native and heterologous expression cell systems. In native rat pituitary
GH3 cells β-ARK/CT, Gαt, and phosducin significantly reduced TRH inhibition of rERG currents, whereas in HEK-H36/T1 cells permanently expressing
TRH-R and hERG, neither of the βγ scavengers affected the TRH-induced shift in V
1/2. Use of specific siRNAs to knock Akt/PKB expression down abolished the TRH effect on HEK-H36/T1 cell hERG, but not on rERG
from GH3 cells. Indeed, wortmannin or long insulin pretreatment also blocked TRH regulation of ERG currents in HEK-H36/T1 but not
in GH3 cells. To determine whether these differences could be related to the amount of TRH-Rs in the cell, we studied the TRH concentration
dependence of the Ca2+ and ERG responses in GH3 cells overexpressing the receptors. The data indicated that independent of the receptor number additional cellular factor(s)
contribute differently to couple the TRH-R to hERG channel modulation in HEK-H36/T1 cells. We conclude that regulation of
ERG currents by TRH and its receptor is transduced in GH3 and HEK-H36/T1 cell systems through common and different elements, and hence that the cell type influences the signalling
pathways involved in the TRH-evoked responses. 相似文献
19.
Kawngwoo Park Kwang Hyon Park Hye Ran Park Jae Meen Lee Yong Hwy Kim Dong-Young Kim Tae-Bin Won Sung Hye Kong Jung Hee Kim Chan Soo Shin Sun Ha Paek 《Journal of Korean medical science》2021,36(15)
BackgroundAlthough long-term dopamine agonist (DA) therapy is recommended as a first-line treatment for prolactinoma, some patients may prefer surgical treatment because of the potential adverse effects of long-term medication, or the desire to become pregnant. This study aimed to determine whether surgical treatment of prolactinomas could be an alternative to DA therapy.MethodsIn this retrospective study, 96 consecutive patients (74 female, 22 male) underwent primary pituitary surgery without long-term DA treatment for prolactinomas at a single institution from 1990 to 2010. All patients underwent primary surgical treatment in the microscopic transsphenoidal approach (TSA).ResultsThe median age and median follow-up period were 31 (16–73) years and 139.1 (12.2–319.6) months, respectively. An initial overall remission was accomplished in 47.9% (46 of 96 patients, 33 macroadenomas, and 13 microadenomas) of patients. DA dose reduction was achieved in all patients after TSA. A better remission rate was independently predicted by lower diagnostic prolactin levels and by a greater extent of surgical resection. Overall remission at the last follow-up was 33.3%, and the overall recurrence rate was 30.4%. The permanent complication rate was 3.1%, and there was no mortality.ConclusionTSA can be considered a safe and potentially curative treatment for selective microprolactinomas as an alternative to treatment with a long-term DA. 相似文献
20.
Pituitary tumors in the elderly 总被引:1,自引:0,他引:1
The present study was designed to investigate the incidence and immunohistochemical characteristics of pituitary tumors in the elderly. In our surgical collection of 1925 cases, we examined tumor tissue from 15 patients over 80 years of age. Pituitaries obtained at routine autopsies from 692 subjects over 80 years of age were also investigated. Of the 15 surgical cases studied, the majority of patients presented with chiasmatic syndromes, likely caused by macroadenomas. Gonadotroph adenomas were the most frequently diagnosed tumor type, followed by null-cell adenomas and oncocytomas. There is only one case with GH cell adenoma. Among 692 autopsy cases, 79 (11.4%) pituitaries were found to contain adenomas in the anterior lobe. In one pituitary, two separate adenomas were detected, hence the number of adenomas in our material was 80. All autopsy cases were microadenomas except one. The mean diameter of adenomas was 2.2 mm. ACTH cell adenomas were the most frequently diagnosed tumor type, followed by PRL cell adenomas and null cell adenomas. The occurrence of pituitary adenomas discovered after routine autopsy in the elderly was common, although these tumors were not found frequently in surgical cases over 80 years of age. Our immunohistochemical study revealed that many tumors contained one or more than one anterior pituitary hormone, although almost all pituitary adenomas were considered to be clinically inactive in surgical and autopsy cases. 相似文献