Characterization of pituitary stem/progenitor cell populations in spontaneous dwarf rats

Abstract

Spontaneous dwarf rat (SDR) is a primary experimental animal model for the study of pituitary dwarfism with a point mutation in the Gh gene encoding growth hormone (GH). In previous studies, SDR has been reported to be associated with the GH deficiency as well as combined hormone deficiencies, the cause of which is unknown. In this study, we focused on the characteristics of pituitary stem/progenitor cell populations, which are a source of hormone-producing cells, in SDR. Immunofluorescence and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analyses confirmed the defects in GH-producing cells, the decreased number of prolactin- and thyroid-stimulating hormone-producing cells, and the increased number of adrenocorticotropic hormone- and luteinizing hormone-producing cells. Additionally, qRT-PCR analysis showed increased Prop1 (an embryonic stem/progenitor cell marker) expression and decreased S100b (a putative adult stem/progenitor cell marker) expression in SDRs. In the pituitary stem/progenitor cell niche, the marginal cell layer, the proportion of SOX2/PROP1-double positive cells was higher in adult SDRs than in adult Sprague Dawley (SD) rats but that of SOX2/S100β-double positive cells was much lower. Furthermore, the number of SOX2/PROP1-double positive cells in SD rats significantly decreased with growth; however, the decrease was smaller in SDRs. In contrast, the number of SOX2/S100β-double positive cells in SD rats significantly increased with growth; however, they were few in SDRs. Thus, S100β-positive pituitary stem/progenitor cells failed to settle in pituitary dwarfism with the Gh gene mutation, leading to multiple hypopituitarism including GH deficiency.