Summary of Session IV Growth Hormone Action

Abstract

How growth hormone (GH) exerts its growth-promoting actions has been a subject of controversy. The debate has centered on whether these effects of GH result from direct action on target cells or are mediated indirectly by stimulation of production of somatomedins/insulin-like growth factors (Sm/IGFs). Resolution of this question now appears to be coming into sight. A variety of lines of evidence suggest that both GH and the Sm/IGFs act sequentially and in concert to promote growth. While it has not been shown to stimulate cellular proliferation directly (erythroid cell being a possible exception), GH causes differentiation of myoblast and preadipocyte cell lines (1). Once differentiated, these cells proliferate readily in response to somatomedin-C/insulin-like growth factor I (SmC/IGF-I) (2). The data presented by Dr. Isaksson and colleagues in this volume strengthen the belief that the sequential action of GH and SmC/IGF-I may be operative also in the growth of chondrocytes. They have shown that GH increases the abundance of SmC/IGF-I messenger RNA (mRNA) and the appearance of SmC/IGF-I immunoreactive cells in the epiphyseal proliferative zone of hypophysectomized rat cartilage. It is likely that SmC/IGF-I then stimulates cellular proliferation and expansion of the epiphysis. SmC/IGF-I and IGF-II have well-documented mitogenic effects on a wide variety of cultured cells. When administered in vivo to hypophysectomized rats, Sm/IGFs can reproduce GH’s growth-promoting actions (see reviews by Doctors Froesch and Hizuka and their co-workers). While SmC/IGF-I seems to mediate the stimulatory effect of GH cellular proliferation, GH probably acts without SmC/IGF-I to stimulate cellular differentiation and a variety of other metabolic events (the latter are reviewed by Dr. Goodman and co-workers).