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Cell type specific expression of the growth hormone gene and its control by GHF-1.

One of the major challenges in molecular genetics is to determine the mechanisms which control the utilization of genetic information in time and space dependent manners. Differential gene activation is the basis for the processes of cellular differentiation and specialization. Through genetic analysis, a great deal has been learned about the general mechanisms which control these processes in organisms such as D. melanogaster and C . elegans . Although mammals, on the other hand, are refractory to genetic analysis, significant progress has been made in understanding the mechanisms involved in determining tissue specific gene expression in these organisms. This can be mostly attributed to a biochemical approach employing in vitro transcription systems in which differential promoter utilization could be observed, resulting in identification of transcription factors mediating cell-type specific gene expression (Scheidereit et al. 1987; Lichtsteiner et al. 1989; Bodner and Karin 1987) . Several of these factors were purified to homogeneity and their cDNAs were cloned (Bodner et al. 1988; Scheidereit et al. 1988) . In this review we will describe our studies on the control of growth hormone (GH) gene expression. A major emphasis will be placed on the mechanisms responsible for the cell type specific expression of this gene. The GH gene family represents an excellent system for studying the mechanisms responsible for cell type specific gene expression (Karin, 1989) . In addition to GH, this family includes several other genes coding for hormones of physiological and clinical importance, such as prolactin (Prl) and the various placental lactogens (PL) (Miller and Eberhardt, 1983) . GH is specifically expressed in specialized cells, the somatotrophs, of the anterior pituitary. It is required for postnatal growth and maintenance of nitrogen, mineral, lipid and carbohydrate metabolism (Martin, 1973) . Its most important function is probably the stimulation of protein synthesis,