Abstract
The gene for human growth hormone (hGH) was introduced into PC12 cells, a rat pheochromocytoma-derived cell line with neuronal characteristics, and stable cell lines were isolated that express this protein. hGH is stored within the cells in membrane-bounded vesicles that are indistinguishable from the endogenous catecholaminergic synaptic vesicles. When the transfected cells are stimulated by carbachol or direct depolarization, they release norepinephrine and hGH with parallel kinetics. Treatment of the transfected cells with nerve growth factor results in a 2-fold increase in the amounts of hGH stored in and secreted from the cells. Not all proteins are packaged into the synaptic vesicles, since the rate of release of laminin, a soluble secreted protein endogenous to PC12 cells, is not stimulated by carbachol. This neuronal cell line therefore possesses at least 2 distinct pathways for secretion and can selectively package a foreign endocrine hormone into the regulated pathway.