GFP-expressing S100β-positive cells of the rat anterior pituitary differentiate into hormone-producing cells

Abstract

Some non-endocrine cells in the pituitary anterior lobe are responsible for providing stem/progenitor cells to maintain hormone-producing cells. In particular, cells expressing S100β protein, a calcium-binding protein, have been hypothesized to be a pituitary cell resource. Accumulating data have revealed that S100β-positive cells comprise heterogeneous populations and some of them certainly show stem/progenitor characteristics in vivo. Hence, we examine whether S100β-positive cells have the capacity to differentiate into endocrine cells, by means of in vivo and in vitro experiments on transgenic rats expressing enhanced green fluorescent protein (EGFP) under the control of the S100β promoter. Immunohistochemistry of the pituitary confirmed that some S100β-positive cells expressed SOX2 (SRY [sex-determining region Y]-box 2) and had proliferative activity. Dispersed anterior lobe cells were observed by time-lapse microscopy, followed by immunostaining for hormone and pituitary-transcription-factor1 (PIT1). First, the dispersed anterior lobe cells were immunostained by an antibody against SOX2. S100β-protein co-localizes with SOX2 (about 89 %). Although 44 of 134 S100β-positive cells traced were proliferative but negative to any hormones, 14 cells were positive for one of the pituitary hormones and/or PIT1, confirming the presence of all types of hormone-producing cells. Notably, GFP-fluorescence appeared in two hormone-positive cells during culture. On the other hand, we observed hormone-producing cells that were not positive for S100β at the end of the time-lapse study, despite being initially positive. These findings suggest that S100β-positive cells cultured from the anterior lobe are capable of developing into hormone-producing cells, although this happens relatively infrequently.

Pituitary Hyperplasia, Hormonal Changes and Prolactinoma Development in Males Exposed to Estrogens—An Insight From Translational Studies

“…Estrogen-induced changes in S100β-immunofluorescent signal indicates a decreased signal in comparison to Orx middle-aged males (Figure 4). Our data, together with finding that FS cells coexpress S100β and SOX2, are in line with the assumption that a subpopulation of FS cells also serves a pool of SP cells [16,51,98]. SOX2 + / SOX9 + cells were reported to proliferate due to the effect of estradiol in vitro, with a predisposition to become lactotropic and luteinizing cells, with a small number differentiating into GH cells [49] (Figure 1).…”

“…Estrogen may affect already-differentiated PRL cells, stem/progenitor cells, lineage-related cells and cells comprising the microenvironment. Transcriptional regulation of the following genes is mainly associated with tumorigenic action of estrogen in the pituitary: pituitary tumor transforming gene (PTTG); Myc; aldehyde dehydrogenase 1A1 (ALDH1A1); D2R, dopamine D2 receptor; mitogen-activated protein kinases (MAPK); vascular endothelial growth factor (VEGF); fibroblast growth factor 2 (FGF2); transforming growth factor β (TGFβ) and other growth factors and cytokines, such as ILs, interleukines [15,16,[40][41][42][43][44][45][46][47][48][49][50][51][52][53].…”

“…SOX2 is generally accepted as the primary marker for SP cells and is often coexpressed with SOX9, with partial overlap of S-100β expression [50,51] (Figure 1). Estrogen-induced changes in S100β-immunofluorescent signal indicates a decreased signal in comparison to Orx middle-aged males (Figure 4).…”

Regulatory System for Stem/Progenitor Cell Niches in the Adult Rodent Pituitary

“…Interestingly, S100β + -cells show multi-functions as phagocytes [ 31 ], supportive cells [ 22 ], cells forming a cell-network via gap junctions [ 32 ], and as cells regulating hormone release [ 33 ]. Notably, about 85% of S100β + -cells are composed of SOX2 + -cells in the adult rat pituitary [ 21 ], and some of them show an ability to differentiate into endocrine cells [ 34 ]. Therefore, a sub-population of S100β + -cells is regarded to be adult pituitary stem/progenitor cells.…”

S100β-Positive Cells of Mesenchymal Origin Reside in the Anterior Lobe of the Embryonic Pituitary Gland

“…As postulated previously, some S100β-positive cells have the ability to differentiate into skeletal muscle cells [ 10 – 12 ]. More recently, we have reported that some S100β-positive cells are able to differentiate into all hormone-producing cell types in the anterior and intermediate lobes [ 13 ]. Despite these new findings, it is not yet clear how S100β-positive cells originate and develop into plural states with diverse roles.…”