Aim of the study is to assess the pathophysiology of the actions of daily growth hormone and long-acting growth hormone in in -vitro models by evaluating JAK2-STAT3, STAT 5, IGF1 and IGFBP signaling pathway. The study also aims to compare the extent of hyperglycemia (as it is the commonest side effect) induced by daily versus long-acting GH. Articular chondrocytes will be obtained from 12 wk old male Wistar rat, cultured and the expression of GH receptor in chondrocytes will be detected. Then recombinant adenovirus GH(Ad-GH) as well as Ad-LAGH will be transfected to one group of chondrocytes. The expression of collagen type II, matrix metallo proteinase 13 (MMP-13) and signal transducer and activator of transcription 3 (STAT3) in each experimental group will be determined by Western blot. The protein expression of MMP-13, the protein expression of collagen type II, phosphorylated STAT3 (P-STAT3) will be compared in both the groups (GH and LAGH). GH can promote the proliferation of chondrocytes and the synthesis of type II collagen, and increase the extracellular matrix, which is achieved by phosphorylated STAT3 protein. The extent of this activation by daily GH and LAGH will be compared. To clarify the nature of the stimulatory effects of GH on articular cartilage, the time-course of changes in the expression of the proto-oncogene, c-myc and IGF-I mRNAs in cultured articular chondrocytes will be examined. GH induced DNA synthesis of articular chondrocytes which could be neutralized by an antibody raised against IGF-I will also be studied. Furthermore, the modulatory effects of GH on the IGF-I autocrine/paracrine axis, including the production of IGF-I and IGFBPs, and IGF-I binding sites will be examined. The pathogenesis of hyperglycemia will be tested by assessing the extent of expression of GLUT transporters and enzymes of gluconeogenesis.