Tissue-Specific Expression of the Growth Hormone Gene and Its Control by Growth Hormone Factor-1

Abstract

This chapter discusses the tissue-specific expression of the growth hormone gene and its control by growth hormone. The GH gene family represents an excellent system for studying the mechanisms responsible for cell-type-specific gene expression. Rodents contain a single GH gene, and primates contain five tandemly linked GH genes. 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 (PLs). The GH and PRL genes arose by duplication of a common precursor. The function of the various PLs is not clear, but they are thought to have a role in lactogenesis, fetal growth, and stimulation of the corpus luteum and to affect carbohydrate and lipid metabolism. All of these hormones function in the control of growth and development through fetal and adult life. Insufficient production of GH leads to growth retardation or dwarfism, while its overproduction before puberty leads to gigantism and to acromegaly after puberty. Insufficient production of PRL causes a failure in lactation. Overproduction of PRL leads to amenorrhea or impotence, and low levels of PLs seem to correlate with fetal-growth retardation. Several different protein factors binding to the GH promoter are detected, of which one is unique to GH-expressing cells. A restricted distribution of the protein—known as GHF-1—suggests that it plays a major role in the pituitary-specific expression of the GH gene. The chapter discusses various features of GHF-1. GHF-1 has a novel type of activation domain that interacts with the components of the transcriptional machinery.