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1.
J Endocrinol ; 183(2): 385-94, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15531726

ABSTRACT

The oncogenic effects of epidermal growth factor (EGF) have long been established. EGF receptor (EGFr) is overexpressed in many types of tumors and constitutes a target for cancer treatment. The pituitary gland is a target of EGF action and it is very likely that EGFr plays a role in pituitary tumor formation and progression. However, there is a controversy in the literature concerning EGFr expression in the different types of pituitary adenomas. In the present study we investigated the expression pattern of the wild type EGFr (EGFrWT) and the constitutively active variant III (EGFrvIII) at the mRNA and protein levels in a large series of pituitary tumors. EGFrWT was found in a high percentage of hormone-secreting tumors, but only in a small fraction of non-functioning pituitary adenomas, while no expression of the EGFrvIII could be detected by nested RT-PCR in any tumor. Among the hormone-secreting adenomas, the highest incidence of EGFr expression was found in Cushing's pituitary adenomas. Furthermore, immunohistochemistry for the phosphorylated EGFr revealed the presence of activated EGFr in most Cushing's adenomas, compared with most pituitary adenomas. Taking into account that downregulation of p27/Kip1 plays a significant role in corticotrope tumorigenesis and that EGFr mitogenic signaling results in decreased p27/Kip1, we searched for a correlation between EGFr expression and p27/Kip1 levels in corticotropinomas. Low p27/Kip1 immunoreactivity was observed in corticotropinomas expressing EGFr. On the other hand, somatotropinomas expressing EGFr had high p27/Kip1 immunoreactivity. These data suggest a corticotrope-specific phenomenon and indicate that EGFr may have a role in the unbalanced growth of corticotrope tumoral cells.


Subject(s)
Adenoma/metabolism , Adrenocorticotropic Hormone/biosynthesis , Cushing Syndrome/metabolism , ErbB Receptors/metabolism , Pituitary Neoplasms/metabolism , Cell Cycle Proteins/analysis , Cell Cycle Proteins/metabolism , Cyclin-Dependent Kinase Inhibitor p27 , Epidermal Growth Factor/metabolism , ErbB Receptors/analysis , ErbB Receptors/genetics , Humans , Immunohistochemistry/methods , Phosphorylation , Pituitary Gland/chemistry , Pituitary Gland/metabolism , Protein Binding , RNA, Messenger/analysis , Reverse Transcriptase Polymerase Chain Reaction , Tumor Suppressor Proteins/analysis , Tumor Suppressor Proteins/metabolism
2.
J Endocrinol ; 167(1): 7-13, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11018748

ABSTRACT

Thyrotrophin (TSH) synthesis and secretion is under the positive control of thyrotrophin releasing hormone and under the negative control of the thyroid hormones. However, it is hypothesised that TSH has a direct effect on the regulation of its own synthesis through an intrapituitary loop mediated by pituitary TSH receptors (TSH-R). The aim of this investigation was to study the expression of TSH-R in normal human pituitary at mRNA and protein levels, and to compare the pattern of protein expression between different pituitary adenomas. Using RT-PCR we were able to detect TSH-R mRNA in the normal pituitary, and immunohistochemical studies showed TSH-R protein expression in distinct areas of the anterior pituitary. Double immunostaining with antibodies against each of the intrapituitary hormones and S100 revealed that TSH-R protein is present in thyrotrophs and folliculostellate cells. Examination of 58 pituitary adenomas, including two clinically active and two clinically inactive thyrotroph adenomas, revealed TSH-R immunopositivity in only the two clinically inactive thyrotroph adenomas. This study shows, for the first time, the presence of TSH-R protein in the normal anterior pituitary and in a subset of thyrotroph adenomas. The expression of TSH-R in the thyrotroph and folliculostellate cell subpopulations provides preliminary evidence of a role for TSH in autocrine and paracrine regulatory pathways within the anterior pituitary gland.


Subject(s)
Adenoma/metabolism , Neoplasm Proteins/metabolism , Pituitary Gland, Anterior/metabolism , Pituitary Neoplasms/metabolism , Receptors, Thyrotropin/metabolism , Animals , Cell Culture Techniques , Cyclic AMP/biosynthesis , Gene Expression , Humans , Immunoenzyme Techniques , Neoplasm Proteins/genetics , RNA, Messenger/genetics , Rats , Rats, Sprague-Dawley , Receptors, Thyrotropin/genetics , Reverse Transcriptase Polymerase Chain Reaction , Thyrotropin/pharmacology , Tumor Cells, Cultured
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