p75^NTR and TrkC Neurotrophin Receptors Demonstrate a Different Immunoreactivity Profile in Comparison to TrkA and TrkB Receptors in Human Normal Pituitary Gland and Adenomas

Abstract

Background/Aims: Recent knowledge indicates that neurotrophins play a significant role in neuroendocrine systems through their specific receptors TrkA, TrkB, TrkC and low-affinity p75^NTR receptor. TrkA and TrkB receptors have been previously detected in numerous endocrine cells in human anterior pituitary and adenomas. In the present study, the localization of p75^NTR and TrkC along with TrkA and TrkB receptors was investigated. Methods: Semi-serial paraffin-embedded sections of 5 human normal pituitaries and 30 adenomas were immunostained using specific antibodies. Results: Expression of p75^NTR receptor was demonstrated in the intricate capillary and reticulin network in the anterior pituitary and in the pericapillary tissue and pituicytes in the posterior lobe. p75^NTR immunoreactivity was absent from all adenomas. In normal anterior pituitary, a few scattered cells showed weak TrkC immunoreactivity in contrast to a high percentage of endocrine cells distributed throughout the pars distalis and pars intermedia which exhibited strong TrkA and/or intermediate TrkB immunoreactivity. Double immunohistochemistry demonstrated TrkA immunoreactivity in more than 80% of lactotropes and 70% of corticotropes and to a lesser extent in other cell types. Furthermore, in the majority of adenomas, independently of type, sex and age, a high percentage of TrkA- and/or TrkB-positive cells was detected. Interestingly, TrkC expression appeared to be increased in some adenomas compared to normal pituitary. Endothelial cells and perivascular connective tissue were always TrkB-immunostained. Conclusion: The above findings support a potential role of all neurotrophins, through their different receptors, in pituitary functions.

Neurotrophins, Their Receptors and KI-67 in Human GH-Secreting Pituitary Adenomas: An Immunohistochemical Analysis

“…However, the localization of the neurotrophin receptors in normal human pituitary gland and their expression in human pituitary adenomas is still unclear. In our observations we described a moderate immunoreaction for NGF, and its relative receptor TrKA and p75NTR, on epithelial glands and less appreciable in the ECM, similar to the experimental observations made by Assimakopoulou et al (13) but different from those of Aguado's et al (14): this suggests a role of NGF and its signaling in the development of normal pituitary gland but not in the progression and proliferation of the pituitary adenomas. BDNF and its receptor TrKB resulted highly appreciable in the ECM and moderate on the vessel endothelium, suggesting their participation in the proliferation of a neoplastic microenvironment, involving the extracellular matrix components and the angiogenetic network, owing to the fact that vascular endothelial cells synthesize and secrete BDNF (32).…”

“…In our observations we described a moderate immunoreaction for NGF, and its relative receptor TrKA and p75NTR, on epithelial glands and less appreciable in the ECM, similar to the experimental observations made by Assimakopoulou et at. (13) but different from those of Aguado's et at. (14): this suggests a role of NGF and its signaling in the development of normal pituitary gland but not in the progression and proliferation of the pituitary adenomas.…”

“…This lineage, comprising somatotroph, mammotroph and thyrotroph cells, is controlled by a common transcription factor named PIT-l (Pituitary-specific positive transcription factor 1). Previous studies suggest that neurotrophins, especially NGF, may be involved in pituitary endocrine cell proliferation, growth and differentiation (13,14). NGF is a particularly interesting neurotrophin in pituitary function and physiology (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18).…”

“…The family of neurotrophins plays a key role in the development and maintenance of nerve cell populations in the peripheral and central nervous system (8)(9)(10)(11)(12). Several lines of evidence suggest that neurotrophins, more particularly NGF, may be involved in pituitary endocrine cell function (13,14). Animal studies have shown that neurotrophins, especially NGF, play a dual role in pituitary physiology.…”

New Insights in the Pathogenesis of Pituitary Tumours

“…NGF is the best characterized neurotrophin in the pituitary and NGF signalling is mediated by TrkA and p75 NTR , a member of the TNF receptor superfamily. All Trk receptors have been observed in the normal pituitary and in PA [140]. NGF plays a role in lactotroph differentiation and in the stress-related stimulation of corticotroph function, and escape to NGF control has been involved in the pathogenesis of prolactinomas.…”