Abstract

Genetic ablation of the NHE2 Na+/H+ exchanger causes gastric achlorhydria, absorptive defects in kidney and colon, and low fertility. Here we show that NHE2 is expressed in the pituitary, with the highest mRNA expression in pars distalis and lower expression in pars intermedia. In pars distalis of NHE2-null mice, prominent cyst-like dilatations of folliculo-stellate (FS) cell canaliculi developed with age, and there were increased FS cell area, accumulation of lipid in FS cell cytoplasm, redundancies in FS cell basement membrane, and other changes. The expansion of the canaliculi indicates that NHE2 is a major absorptive Na+/H+ exchanger in the luminal membranes lining the extensive network of channels formed by FS cells, which may provide a means of intrapituitary communication. The results suggest that NHE2 contributes to homeostatic regulation of the volume and composition of the canalicular fluid and may counter the secretory activity of the CFTR Cl− channel, which is known to be expressed in pituitary.

Highlights

  • The pars distalis of the pituitary is composed of both granular and agranular cell types, the former largely hormoneproducing cells [1], the latter forming a reticular and canalicular network in and around the granulated cells

  • FS cells play a regulatory role both by secretion of paracrine factors, including activin, follistatin, and vascular endothelial growth factor [7, 8], and by intercellular communication via Ca2+ signals transmitted through gap junctions [9], which has been suggested to contribute to synchronization of hormone secretion by endocrine cells [9, 10]

  • The most prominent histological finding consequent to gene-targeted ablation of the NHE2 Na+/H+ exchanger was the dilation of the canaliculi formed by FS cells in the pars distalis of the anterior pituitary

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Summary

Introduction

The pars distalis of the pituitary is composed of both granular and agranular cell types, the former largely hormoneproducing cells [1], the latter forming a reticular and canalicular network in and around the granulated cells. Neighboring FS cells are joined by well-developed junctional complexes forming an interconnected network of channels extending throughout the anterior pituitary, but the pars distalis [2, 3]. Growth, stress, immunity, and reproduction are under the direct influence of granular cell secretions of the pars distalis [7]; the contribution of FS cells to intrapituitary communication and the mode(s) by which this occurs are less well understood. A potential additional means of intrapituitary communication that could play a role in coordination of both FS cell and endocrine cell activities is the network of channels formed by the FS cells

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