Secretagogue induction of GH release in QNR/D cells: Prevention of cell death

Retinal ganglion cells (RGCs) in the chick embryonic neural retina are extrapituitary sites of growth hormone (GH) synthesis and release. The regulation of GH secretion by these cells is largely unknown, although we recently discovered several of the hypothalamic releasing factors involved in pituitary GH regulation (including GH-releasing hormone (GHRH) and thyrotropin releasing hormone, TRH) to be present in the cytoplasm of immortalized quail RGCs (QNR/D cells). QNR/D cells may therefore provide an experimental model for studies on GH regulation in the chick neural retina. The possibility that GHRH and TRH might stimulate GH secretion in QNR/D cells was therefore investigated. Both peptides acutely depleted the GH content of the QNR/D cells, as demonstrated by immunocytochemistry and ELISA, whilst increasing the GH content in incubation media. Both peptides also increased the immunochemical and ELISA content of the QNR/D cells and the content of GH in the incubation media after long-term incubation. Cell survival, determined by metabolic activity of the QNR/D cells and by TUNEL-labeling, was reduced when the endogenous GH content was reduced by GH immunoneutralization, even in the presence of exogenous GHRH or TRH. Cell survival was also reduced when endogenous GHRH was blocked by GHRH immunoneutralization, although the immunoneutralization of endogenous TRH did not affect QNR/D cell survival. In summary, these results demonstrate secretagogue actions of exogenous GHRH and TRH on the secretion of GH from QNR/D cells. They also suggest that endogenous GHRH, but not endogenous TRH, prevents cell death by increasing endogenous GH secretion in QNR/D cells.