共查询到20条相似文献,搜索用时 31 毫秒
1.
Coexpression of galanin and adrenocorticotropic hormone in human pituitary and pituitary adenomas.
下载免费PDF全文
![点击此处可从《The American journal of pathology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
D. W. Hsu S. C. Hooi E. T. Hedley-Whyte R. M. Strauss L. M. Kaplan 《The American journal of pathology》1991,138(4):897-909
Galanin is a neuropeptide that regulates the secretion of several pituitary hormones, including prolactin (PRL) and growth hormone (GH). Galaninlike immunoreactivity (Gal-IR) and galanin mRNA in the rat anterior pituitary is cell lineage specific, with predominant expression in lactotrophs and somatotrophs. The authors examined the cellular distribution of human Gal-IR in seven normal postmortem pituitaries and 62 pituitary tumors by immunoperoxidase staining. In contrast to the rat, Gal-IR in human anterior pituitaries was present in corticotrophs scattered throughout the gland, but not in lactotrophs, somatotrophs, thyrotrophs, or gonadotrophs. Distinct Gal-IR also was present in hyperplastic and neoplastic corticotrophs in 19 of 22 patients with Cushing's disease. In noncorticotroph cell tumors, unequivocal Gal-IR was present in 5 of 11 GH-secreting tumors associated with clinical acromegaly, 9 of 18 nonfunctioning pituitary adenomas, and 2 of 14 prolactinomas. Of these galanin-positive tumors, four of the five GH-secreting adenomas, six of the nine nonfunctioning adenomas, and both of the prolactinomas also contained adrenocorticotropic hormone immunoreactivity (ACTH-IR). Immunostaining and in situ hybridization on adjacent sections using an 35S-labeled probe complementary to human galanin mRNA demonstrated predominant galanin expression in normal corticotrophs. Immunoelectron microscopy confirmed the presence of Gal-IR in pituitary cells characteristic of corticotrophs in both normal and neoplastic pituitaries. Thus, as in the rat, galanin gene expression in the human pituitary is cell-type specific. Unlike the rat, however, human galanin gene expression is restricted to the corticotroph lineage. Studies of tumors confirmed the observed coexpression of galanin and adrenocorticotropic hormone. The divergent cell type specificity of galanin production in human and rat pituitaries reflects different patterns of gene activation in these two species. In addition, these results suggest that galanin in the human pituitary may participate locally in the regulation of the hypothalamic-pituitary-adrenal axis. 相似文献
2.
Pituitary adenomas. An immunohistochemical study of hormone production and chromogranin localization. 总被引:2,自引:0,他引:2
下载免费PDF全文
![点击此处可从《The American journal of pathology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
D. B. DeStephano R. V. Lloyd A. M. Pike B. S. Wilson 《The American journal of pathology》1984,116(3):464-472
Tumors from 42 surgically resected pituitaries and from 13 autopsy cases were studied immunohistochemically with polyclonal antisera to 7 anterior pituitary hormones and with a newly developed monoclonal antibody directed against human chromogranin for evaluation of the distribution of chromogranin in normal and neoplastic pituitaries. In addition, a prospective study was done for assessment of the prevalence, morphology, and endocrine cell types of pituitary tumors in 100 autopsy subjects. When these 55 pituitary adenomas were examined with monoclonal antibody (LK2H10) directed against human chromogranin, selective staining of normal adenohypophyseal cell types and pituitary tumors was observed. Most null-cell adenomas (12/14) were positive for chromogranin, whereas all prolactin (PRL)-producing adenomas (19/19) were negative. Growth hormone (GH) adenomas were focally positive (9/9). All oncocytomas (2/2), 1 thyrotropin (TSH) adenoma, and a follicle-stimulating hormone/luteinizing hormone adenoma were positive for chromogranin. One or more adenomas were present in 14% of the autopsy cases. The tumors occurred most frequently in patients in the fifth through the seventh decades of life. Immunohistochemical staining of 13 adenomas revealed 1 TSH, 1 ACTH, and 4 PRL-producing tumors, whereas 7 other tumors, which were null-cell or undifferentiated adenomas, failed to stain for any of the seven principle pituitary hormones. These results indicate that antibody LK2H10 to human chromogranin is useful in the immunohistochemical characterization of pituitary adenomas. Incidental pituitary microadenomas from autopsy-derived pituitaries most commonly produce PRL, or they belong to the null-cell or undifferentiated tumor group. 相似文献
3.
Epidermal growth factor (EGF) and epidermal growth factor receptor (EGFr) were investigated by immunocytochemistry (ICH) in
57 human pituitary adenomas and 10 nontumorous autopsy pituitaries. EGF immunoreactivity was demonstrated in 24 adenomas (42%),
representing 23 functioning tumors and 1 nonfunctioning tumor of oncocytic type, and in all nontumorous pituitaries. Among
40 tumors, EGFr was found positive in 15 functioning adenomas (37.5%), representing 50% of them. The presence of both EGF
and EGFr was found mainly in corticotroph adenomas (60%) and less frequently in somatotroph and lactotroph adenomas (20%).
ICH on serial sections with EGF or EGFr and adrenocorticotrophic hormone (ACTH) or S-100 protein revealed that EGF and EGFr
are localized specifically in corticotrophs and EGFr in stellate cells of nontumorous adenohypophysis.
These results confirm the presence of EGF and EGFr in human pituitary adenomas and nontumorous pituitaries and highlight their
frequent occurrence in hormone-producing adenomas. Further work is required to explore the possibility that EGF and EGFr play
a role in hormone production, release, and tumor progression. 相似文献
4.
Rab proteins are low molecular weight GTP-binding proteins. Among these proteins, the Rab3 isoforms are considered to be involved in the exocytosis of synaptic vesicles and secretory granules in the central nervous system and anterior pituitary gland. In recent reports, the expression of Rab3 isoforms in anterior pituitary glands of mammalian species was extensively investigated. In the present study, we investigated the localization of Rab3 protein in 5 human nontumorous pituitaries and 114 human pituitary adenomas using immunohistochemical methods. In five human nontumorous pituitaries, Rab3 protein was expressed in the cytoplasm of anterior pituitary cells. Double staining for anterior pituitary hormones revealed the expression of Rab3 in growth hormone-secreting cells, but rare expression was observed in the other anterior pituitary hormone-secreting cells. Among the pituitary adenomas, 71 (62.3%) of 114 pituitary adenomas were positive for Rab3. Among the different pituitary adenoma types, the incidence of Rab3 immunopositivity was highest in growth hormone-secreting adenomas (100%), followed by adrenocorticotropic hormone-secreting adenomas (71.4%), thyroid-stimulating hormone-secreting adenomas (57.1%), nonfunctioning adenomas (56.0%), and prolactin-secreting adenomas (33.3%). After an embedding immunoelectron microscopic study, Rab3 was localized along the limiting membrane of secretory granules in the Rab3-positive pituitary adenomas. Western blotting showed the molecular weight of Rab3 to be 25 kDa in the pituitary adenomas, which were immunohistochemically positive for Rab3 protein. These results suggested that Rab3 might be involved in regulating the exocytosis of secretory granules of the anterior pituitary cells, especially growth hormone-secreting ones, which are particularly characterized by densely granulated cytologic features. 相似文献
5.
6.
Makoto Sugiyama MD Naoko Sanno MD PhD Akira Teramoto MD R. Yoshiyuki Osamura MD PhD 《Endocrine pathology》1998,9(2):125-134
Inhibin and activin are gonadal hormones produced in human ovaries. They are known to act on anterior pituitary cells to regulate
the synthesis and secretion of follicle-stimulating hormone (FSH). The purpose of the present study was to determine the localization
of inhibin and activin subunits α and βA as endocrine markers in the human normal pituitary gland and pituitary adenomas,
using immunohistochemistry andin situ hybridization (ISH) methods.
Pituitary tissues from surgical and autopsy materials were fixed in 10% formalin and embedded in paraffin. Five normal pituitary
glands and 79 pituitary adenomas were immunostained with the avidin-biotin peroxidase complex (ABC) method using polyclonal
antibodies against inhibin and activin subunits α and βA. The other antibodies against anterior pituitary hormones used in
this study were as follows: antigrowth hormone (anti-GH), antiprolactin (anti-PRL), antiadrenocorticotropic hormone (anti-ACTH),
anti-FSHβ, antilutenizing hormone (anti-LH) β, antithyroid-stimulating hormone (anti-TSH) β, and antiglycoprotein α-subunit
(anti-α-SU).
We analyzed gene expressions of subunits α and βA by nonradioisotopic ISH in pituitary adenomas. In the normal human pituitary
glands, inhibin and activin subunits α and βA immunoreactivities were found diffusely in the cytoplasm of anterior pituitary
cells. The percentage of subunit α-immunopositive cells was 40% of the anterior pituitary cells. Subunit βA immunoreactivities
were observed in about 15% of the anterior pituitary cells. By the double-staining method, subunit α immunoreactivity was
detected in all types of anterior pituitary cells, and it was colocalized most frequently with GH and α-SU-positive cells.
Subunit βA immunoreactivity was colocalized predominantly with PRL, FSH-β, LH-β, and α-SU.
Among the 79 adenomas, 75 cases (94.9%) were positive for subunit α, and 50 cases (63.3%) were positive for subunit βA. Subunit
βA was positive in tumor cells with the following incidences: GH adenomas, 3 of 14 (21.4%); PRL adenomas, 5 of 8 (62.5%);
ACTH adenomas, 6 of 6 (100%); TSH adenomas, 7 of 7 (100%); nonfunctioning adenomas, 29 of 44 (65.9%), including gonadotropin-positive,
16 of 22 (80.0%). The ISH signals for subunits α and βA were strongly expressed in gonadotropin-positive adenomas among the
nonfunctioning adenomas. The mRNA signals were low and infrequent in the GH-producing adenomas.
Inhibin and activin subunit α localization did not demonstrate cell-type specificity in pituitary adenomas. In contrast, subunit
βA demonstrated predominant positivity in the functioning pituitary adenomas (ACTH- and TSH-secreting) and nonfunctioning
adenomas (including gonadotropin-positive adenomas). The present results suggest that the functional role of inhibin and activin
in the differentiation of cells in normal human pituitary glands and adenomas is present in subunit βA. 相似文献
7.
Toshiko Sumi Lucia Stefaneanu Kalman Kovacs Sylvia L. Asa Guido Rindi 《Endocrine pathology》1993,4(2):95-99
In many human cancers, p53 gene mutations are frequently occurring genetic abnormalities, which may be detected by immunohistochemical
staining for p53 protein. In the present study, p53 immunoreactivity was investigated in formalin-fixed, paraffin-embedded
tissues from human and animal pituitary tumors, using the avidin-biotin-peroxidase complex technique. No p53 was detected
in 3 nontumorous human adenohypophyses or in 40 human pituitary tumors including 5 GH cell adenomas, 10 PRL cell adenomas,
2 mixed GH cell-PRL cell adenomas, 2 acidophil stem cell adenomas, 8 ACTH cell adenomas, 1 TSH cell adenoma, 1 FSH/LH cell
adenoma, 5 null cell adenomas, 5 oncocytomas, and 1 plurihormonal adenoma. Twenty nontumorous and hyperplastic pituitaries
of hGRH transgenic mice and 8 tumors in these transgenic animals were immunonegative for p53. All pituitary tumors found in
AVP/SV40 transgenic mice contained p53 immunoreactivity in the nuclei, while the nontumorous adenohypophysis of one such transgenic
mouse was negative. It can be concluded that p53 mutations are apparently not involved in the pathogenesis of human pituitary
adenomas or of the pituitary tumors which develop in hGRH transgenic mice. However, pituitary tumors in AVP/ SV40 transgenic
mice are accompanied by p53 expression. 相似文献
8.
Protein kinase C (PKC) is involved in the differentiation and growth regulation of a variety of tissues including anterior pituitary gland cells. To determine the distribution of PKC in different types of adenomas, PKC activity was analyzed in human pituitary tumors and the effects of hypothalamic hormone stimulation on PKC activity were examined in cultured adenoma cells. Gonadotroph (LH/FSH) and null cell adenomas had significantly higher levels of particulate, soluble, and total PKC activity compared with growth hormone (GH) adenomas (P < 0.05). Chronic stimulation of null cell adenomas with gonadotropin hormone-releasing hormone or of one GH adenoma with GH-releasing hormone for 7 days did not significantly alter total PKC activity in pituitary cells cultured in serum-free medium. Localization of the calcium-dependent PKC isozymes (alpha, beta and gamma) by immunohistochemistry and in situ hybridization revealed predominantly PKC alpha in all adenomas and variable expression of PKC beta and gamma in some tumors. When the calcium-independent PKC isozymes (delta, epsilon, and zeta) were localized by in situ hybridization, normal and neoplastic pituitaries expressed abundant mRNA for PKC epsilon, whereas some tumors and one normal pituitary had a few cells positive for PKC zeta mRNA as evaluated by grain density and the number of cells labeled. These results indicate that there is a variable distribution of PKC mRNA isozymes in human pituitary adenomas and that normal pituitaries and pituitary adenoma cells express the mRNA for both the calcium-dependent and some of the calcium-independent PKC isozymes. Chronic treatment with the hypothalamic gonadotropin hormone-releasing hormone and GH-releasing hormone, which increased LH/FSH and GH secretion, respectively, did not increase PKC activity in cultured adenoma cells. The presence of calcium-dependent and calcium-independent PKC isozymes in normal and neoplastic pituitary cells indicates that PKC probably plays a major role in signal transduction in the human pituitary adenomas examined in this study. 相似文献
9.
Pituitary adenomas and granular cell tumors. Incidence, cell type, and location of tumor in 100 pituitary glands at autopsy. 总被引:2,自引:0,他引:2
Incidentally detected pituitary adenomas were investigated in 100 pituitary glands at autopsy to determine the number, cell type, and location of tumors, and the presence of coexisting granular cell tumors in the neurohypophysis. Pituitary glands were sagittally sectioned at 1.5-mm intervals in toto and embedded in 1 cassette to orient location of each tumor. Twenty-four pituitary glands harbored adenomas, most smaller than 3 mm and the largest 6 x 5 x 4 mm. Two pituitary glands contained double adenomas of immunocytochemically different cell types. Of the 26 adenomas, 10 had lactotrophs, 2 had mixed lactotrophs-somatotrophs, 1 had mixed lactotrophs-luteinizing hormone cells, and 12 were nonfunctioning. One adenoma with adenocorticotropic hormone cells was also detected. Thus 25 of 26 (96%) adenomas were either lactotrophic or nonfunctioning; this percentage is much higher than that of surgically resected tumors. Twenty-two tumors were contiguous with or adjacent to the capsule from which the adenomas originated. Nine granular cell tumors were noted in the neurohypophysis; 3 coexisted with pituitary adenomas. Fourteen additional cases revealed small granular cell nests. Thus the incidental finding of nonfunctioning pituitary adenomas is relatively common in adults (24% of cases in this study), and the coexistence of pituitary adenomas and granular cell tumors may suggest a possible histogenic connection between anterior and posterior pituitary tumorigenesis. 相似文献
10.
Silencing of the imprinted DLK1-MEG3 locus in human clinically nonfunctioning pituitary adenomas 总被引:1,自引:0,他引:1
Cheunsuchon P Zhou Y Zhang X Lee H Chen W Nakayama Y Rice KA Tessa Hedley-Whyte E Swearingen B Klibanski A 《The American journal of pathology》2011,179(4):2120-2130
DLK1-MEG3 is an imprinted locus consisting of multiple maternally expressed noncoding RNA genes and paternally expressed protein-coding genes. The expression of maternally expressed gene 3 (MEG3) is selectively lost in clinically nonfunctioning adenomas (NFAs) of gonadotroph origin; however, expression status of other genes at this locus in human pituitary adenomas has not previously been reported. Using quantitative real-time RT-PCR, we evaluated expression of 24 genes from the DLK1-MEG3 locus in 44 human pituitary adenomas (25 NFAs, 7 ACTH-secreting, 7 GH-secreting, and 5 PRL-secreting adenomas) and 10 normal pituitaries. The effects on cell proliferation of five miRNAs whose expression was lost in NFAs were investigated by flow cytometry analysis. We found that 18 genes, including 13 miRNAs at the DLK1-MEG3 locus, were significantly down-regulated in human NFAs. In ACTH-secreting and PRL-secreting adenomas, 12 and 7 genes were significantly down-regulated, respectively; no genes were significantly down-regulated in GH-secreting tumors. One of the five miRNAs tested induced cell cycle arrest at the G2/M phase in PDFS cells derived from a human NFA. Our data indicate that the DLK1-MEG3 locus is silenced in NFAs. The growth suppression by miRNAs in PDFS cells is consistent with the hypothesis that the DLK1-MEG3 locus plays a tumor suppressor role in human NFAs. 相似文献
11.
Katharina H. Ruebel BS Long Jin MD Shuya Zhang BS Bernd W. Scheithauer MD Dr. Ricardo V. Lloyd MD PhD 《Endocrine pathology》2001,12(3):281-289
Recent studies have shown that methylation of the CpG island within the p16/CDKN2A/MTS1 (p16) gene is associated with loss
of expression of p16 protein in pituitary tumors. We analyzed a series of 21 pituitary adenomas and three normal pituitaries
along with a human pituitary cell line (HP75) for methylation of exon 1 by methylation-specific PCR, immunohistochemistry,
and Western blotting. PCR analysis showed that 5/7 (71%) of null cell adenomas, but only 2/7 (29%) gonadotroph tumors were
hypermethylated. In addition, 1 of 2 ACTH tumors but no GH (n=4) or PRL (n=1) adenoma examined were hypermethylated. Immunostaining and Western blot analysis of protein expression supported the methylation-specific
PCR analyses.
These results show that p16 gene silencing by hypermethylation is more common in null cell adenomas compared to other nonfunctioning
adenomas such as gonadotroph tumors and that the role of p16 in the pathogenesis of pituitary adenomas is restricted to specific
tumor subtypes.
Supported in part by NIH CA90249 and by a grant from the Jarislowsky Foundation. 相似文献
12.
Growth hormone-releasing hormone receptor mRNA in acromegalic pituitary tumors. 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《The American journal of pathology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
M. B. Lopes B. D. Gaylinn M. O. Thorner M. H. Stoler 《The American journal of pathology》1997,150(6):1885-1891
The growth hormone (GH)-releasing hormone receptor (GHRH-R) has been recently cloned and found to be a member of a new family of seven transmembrane receptors that includes secretin, vasoactive intestinal peptide, calcitonin, and corticotropin-releasing factor. GHRH-R mRNA has been demonstrated by Northern blot analyses to be present specifically in the anterior pituitary gland. To determine the precise cellular localization of this receptor in normal anterior pituitary and pituitary adenomas, GHRH-R mRNA was analyzed in 2 normal human pituitary glands and 16 human pituitary adenomas using in situ hybridization. GHRH-R was specifically localized in somatotroph cells in the normal pituitary. In the adenomas, all GH-producing adenomas originating from acromegalic patients demonstrated up-regulation of GHRH-R mRNA when compared with levels in the normal pituitary. Only one of five clinically nonfunctioning adenomas, a gonadotroph luteinizing hormone/follicle-stimulating hormone-positive adenoma, exhibited up-regulation of this receptor message. Adrenocorticotrophic hormone-secreting and prolactin-secreting adenomas did not express GHRH-R message. In summary, GHRH-R is specifically expressed in somatotrophs and GH-producing adenomas, suggesting that GHRH-R may influence GH release in adenomas similar to this receptor's actions in the normal somatotrophs and may be involved in the growth of GH-secreting adenomas. 相似文献
13.
Although recent molecular investigations have identified a number of genetic alterations that are associated with the development of pituitary adenomas, the exact pathogenesis mechanism of these tumors remains largely unknown. In this study, we used a genome-wide survey to detect specific genetic changes within the genome of pituitary adenomas. A series of 10 growth hormone-secreting adenomas were analyzed for their genetic imbalances on all 22 autosomes by comparative genomic hybridization (CGH). Chromosomal imbalances were detected in 8 GH-secreting adenomas, whereas 2 tumors had no detectable genetic abnormalities. Chromosome gains were more frequent than losses. Overrepresentation of whole or parts of chromosomes were detected in 5/10 (50%) in 19, 3/10 (30%) in each of 5, 9, and 22q, 2/10 (20%) in 17p12-q21, whereas DNA loss were 3/10 (30%) in 13q and 2/10 (20%) in 18. No detectable gain or loss of genetic material was observed in chromosomes 7, 8, 10, 12, 15, and 20. The findings of overrepresentation of chromosomes 5q, 9p, 17q and DNA loss of chromosome 18 were consistent with those detected in nonfunctioning adenomas (Daniely M, Aviram A, Adams EF, et al:J Clin Endocrinol Metab 83:1801-1805, 1998) suggesting that the development of pituitary tumors, at least in somatotroph and nonfunctioning adenomas, may share common pathway. Frequent amplifications in chromosomes 19 and 22q imply that candidate genes residing in these chromosomal regions may be involved in the pathogenesis of GH-secreting adenomas. 相似文献
14.
In situ hybridization (ISH), which can manifest the specific gene expression of anterior pituitary hormones (mRNA), as well as immunohistochemistry (IHC), is needed to clarify the endocrine function of pituitary adenomas. With the aid of nonisotopic ISH, which has several advantages over isotopic ISH, we examined the expression of pituitary hormone mRNAs in 14 clinically nonfunctioning adenomas, which were considered to be a subtype of gonadotroph adenomas. Gene expression of growth hormone (GH; 4/14), prolactin (PRL; 5/14), adrenocorticotroph hormone (ACTH; 4/14), and gonadotropin were detected with our nonisotopic ISH studies. It is suggested from our ISH studies that some clinically nonfunctioning adenomas are composed of hormone (or subunit) producing cells and may be derived from plurihormonal primordial stem cells. 相似文献
15.
Ricardo V. Lloyd Constance J. D’Amato Michelle T. Thiny Long Jin Samuel P. Hicks William F. Chandler 《Endocrine pathology》1993,4(2):86-94
Corticotroph (basophil) invasion or the migration of corticotroph cells into the pars nervosa of the human pituitary gland was found in 35 of 767 (4.4%) consecutive pituitaries obtained at autopsy. The degree of invasion increased with patient age and extensive invasion was more common in men than in women. Immunoreactive ACTH, β-MSH, α-MSH, and galanin were detected both in the anterior lobe and invading corticotroph cells in approximately equal frequency. Fewer cells stained positively for α-MSH than for the three other peptides in both the anterior lobe and invading corticotrophs. Twelve corticotropic pituitary adenomas obtained surgically from patients with Cushing’s disease were also examined and expressed varying degrees of immunoreactivity for ACTH, α MSH, β-MSH and galanin. Staining for all major pituitary hormones revealed only ACTH in the invading basophil cells. Peptidylglycine α-amidating monooxygenase (PAM) was present in the anterior pituitary, in invading corticotroph cells, and in some cells lining the cysts of the pars intermedia zone. PAM immunoreactivity was also detected in 4/12 corticotroph adenomas. These results indicate that corticotroph cells invading the pars nervosa are immunohistochemically similar to anterior lobe corticotrophs and have the ability to amidate various peptides such as proopiomelanocortin cleavage products and galanin with PAM. 相似文献
16.
Rotondo F Vidal S Bell D Horvath E Kovacs K Scheithauer BW Lloyd RV 《Acta histochemica》2003,105(4):303-307
The aim of the present study was to investigate immunohistochemically expression of amylin, a 37 amino acid peptide, cosecreted with insulin by beta cells in pancreatic islets in 12 non-tumorous pancreatic tissues, 22 pancreatic islet tumors, 14 non-tumorous thyroids, 14 medullary carcinomas of the thyroid, 10 non-tumorous pituitaries and 50 pituitary adenomas including 10 amyloid-forming prolactin-cell adenomas using the streptavidin-biotin-peroxidase complex method. Amylin was expressed in non-tumorous pancreatic islets but not in non-tumorous thyroids and pituitaries. Since amylin plays an important role in amyloid formation in pancreatic islets, those tumor types were selected to study which may produce amyloid. Amylin was widely expressed in one insulin producing beta cell tumor. Few tumor cells were immunopositive in 8 islet-cell tumors and in 5 medullary thyroid carcinomas. Immunostaining was not found in pituitary adenomas, including those which produced amyloid. It can be concluded that amylin is not a satisfactory immunohistochemical marker to identify pancreatic islet tumors, medullary thyroid carcinomas and pituitary adenomas. 相似文献
17.
Detection of gonadotropin-releasing hormone receptor in normal human pituitary cells and pituitary adenomas using immunohistochemistry 总被引:1,自引:0,他引:1
La Rosa S Celato N Uccella S Capella C 《Virchows Archiv : an international journal of pathology》2000,437(3):264-269
Gonadotropin-releasing hormone (GnRH), which is a well-known regulator of gonadotroph function, has recently been considered
to be a paracrine factor involved in the control of somatotroph, lactotroph, and corticotroph cells. GnRH action is initiated
by binding to a specific cell surface receptor, the gonadotropin-releasing hormone receptor (GnRHR), which is expressed by
follicle-stimulating hormone/luteinizing hormone (FSH/LH) cells. Using in situ hybridization techniques, GnRHR messenger ribonucleic
acid (mRNA) has recently been detected in normal human anterior pituitary gland and in various pituitary adenomas, including
FSH/LH-cell, growth hormone (GH)-cell, adrenocorticotropic hormone (ACTH)-cell, and null-cell adenomas. However, immunohistochemical
studies indicating the specific cell distribution of GnRHR in normal pituitary cells have never been reported. The aim of
the present investigation was to evaluate the immunohistochemical expression of GnRHR in different types of normal pituitary
cells and related tumors. Using double-label immunohistochemical techniques on formalin-fixed and paraffin-embedded tissues
and specific antibodies directed against pituitary hormones and GnRHR, we found GnRHR immunoreactivity not only in FSH/LH
cells, but also in GH- and thyroid-stimulating hormone (TSH) cells. GnRHR was detected in FSH/LH-cell, GH-cell, mixed GH-
and prolactin (PRL)-cell, and α-subunit (α-SU)/null-cell adenomas. The findings of this study suggest that the interaction
between GnRH and GnRHR may play a role in paracrine/autocrine regulation of different types of normal pituitary cells and
pituitary adenomas.
Received: 24 January 2000 / Accepted: 12 April 2000 相似文献
18.
Lucia Stefaneanu Kalman Kovacs Eva Horvath Ricardo V. Lloyd 《Virchows Archiv : an international journal of pathology》1991,419(2):107-113
Summary Pro-opiomelanocortin (POMC) mRNA was detected on paraffin sections by in situ hybridization (ISH) in corticotrophs of 12 nontumorous pituitaries, 11 functioning corticotroph, and 11 silent pituitary adenomas. ISH combined with immunocytochemistry for adrenocorticotrophic hormone (ACTH), a POMC-derived peptide, was also performed. ACTH immunoreactive cells of the anterior lobes and those invading the posterior lobe showed a high or moderate level of POMC mRNA that was not correlated with the intensity of ACTH immunoreactivity. Variable levels of POMC gene expression were present in Crooke's cells, corticotrophs suppressed by glucocorticoid excess. Most functioning corticotroph adenomas and silent subtype 1 adenomas had an intense hybridization signal and ACTH immunoreactivity. In silent subtype 2 and 3 adenomas, POMC mRNA had a diffuse low level or was absent; in these adenomas ACTH immunoreactivity was diffuse, restricted to some cells, or negative. The results indicate that POMC gene is expressed in both normal and suppressed nontumorous corticotrophs. Intense signals for POMC mRNA are found in most functioning corticotroph adenomas. The difference between POMC gene expression in silent 1 and silent 2 and 3 adenomas suggests that different mechanisms are responsible for the lack of endocrine activity. 相似文献
19.
20.
Alberto Righi Shuya Zhang Long Jin Bernd W. Scheithauer Kalman Kovacs Gabor Kovacs Miklos I. Goth Marta Korbonits Ricardo V. Lloyd 《Endocrine pathology》2010,21(1):25-31
Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is an oncofetal protein highly expressed in fetal tissue and malignant
tumors but rarely found in adult benign tissues. In various tumors, IMP3 expression is correlated with increased tumor aggressiveness
and reduced overall survival. To our knowledge, IMP3 expression has not been investigated in pituitary tumors. We analyzed
the immunohistochemical expression of IMP3 in five normal pituitary tissues and 75 pituitary tumors (64 adenomas and 11 carcinomas)
to determine if specific tumor types expressed IMP3 and if there were differences in IMP3 expression between adenomas and
carcinomas. Immunohistochemical analysis showed that IMP3 was positive in four (80%) normal pituitaries with focal stain in
a subset of normal anterior pituitary cells. IMP3 was expressed in 31% (20/64) of adenomas and in 36% (4/11) of carcinomas.
A slightly higher level of IMP3 expression was observed in PRL-GH-TSH adenomas compared to the other types of pituitary adenomas.
Expression of IMP3 was not significantly higher in carcinomas than in adenomas (p = 0.737). RT-PCR and Western Blotting supported the heterogeneous expression of IMP3. These results indicate that IMP3 is
expressed both in normal and in neoplastic pituitary gland tissues without significant differences in expression levels in
pituitary carcinomas. 相似文献