Internalization of the chicken growth hormone receptor complex and its effect on biological functions

In the chicken, as in mammals, GH is a pleiotropic cytokine that plays a central role in growth differentiation and metabolism by altering gene expression in target cells. In the growing and adult chicken it stimulates gene expression of IGF-I and inhibits gene transcription of the type III deiodinating enzyme (D3) and by doing so also increases T(3) concentrations. GH binding to its receptor leads to internalization of the GH-GHR complex to the Golgi apparatus. This process is linked to the episodic release pattern of GH during growth. At the same time, a sharp decline of the expression of cGHR occurs at hatching. An in vitro study using a COS-7 cell line transfected with the cDNA of the chicken GHR, revealed that GHR immunofluorescence was found in the perinuclear region and on the plasma membrane. Following GH-induced internalization, GH and GHR were colocalized in endocytic and later in large lysosomal vesicles. Neither receptor nor ligand was transferred to the nucleus as confirmed by confocal laser microscopy. The JAK/STAT pathway however, as reported for mammalian GH receptors, mediated GH-induced gene transcription in chickens.