Growth hormone (GH) is a survival rather than a proliferative factor for embryonic striatal neural precursor cells

Abstract

ObjectiveA possible role of GH during central nervous system (CNS) development has been suggested by the presence of this hormone and its receptor in brain areas before its production by the pituitary gland. Although several effects have been reported for GH, the specific role of this hormone during CNS development remains unclear. Here, we examined the effect of GH on proliferation, survival and neurosphere formation in primary cultures of striatal tissue from14-day-old (E14) mouse embryos. DesignGH receptor gene expression was confirmed by RT-PCR. Primary cultures of embryonic striatal cells were treated with different doses of GH in serum free media, then the number of neurospheres was determined. To examine the GH effect on proliferation and survival of the striatal primary cultures, bromodeoxyuridine (BrdU) and TUNEL immunoreactivity was conducted. ResultsIn the presence of the epidermal growth factor (EGF), GH increased the formation of neurospheres, with a maximal response at 10ng/ml, higher doses were inhibitory. In absence of EGF, GH failed to stimulate neurosphere formation. Proliferation rate in the primary striatal cultures was inhibited by 24 or 48h incubation with GH. However, in the absence of EGF, GH increased BrdU incorporation. GH treatment decreases the rate of apoptosis of nestin and GFAP positive cells in the primary striatal cultures, enhancing neurosphere formation. ConclusionsOur in vitro data demonstrate that GH plays a survival role on the original population of embryonic striatal cells, improving Neural Precursor Cells (NPCs) expansion. We suggest that this GH action could be predominant during striatal neurodevelopment.