Gestational Physiology of the Growth Hormone Gene Family

The human growth hormone (hGH) gene family, located in a cluster spanning 48 kb on chromosome 17q22–24 (1), contains 5 genes: the pituitary GH gene (hGH-N) and 4 placentally expressed genes, chorionic somatomammotropin-like (hCS-L), hCS-A, hGH-variant (hGH-V), and hCS-B (2). These genes evolved by a series of duplication events, the most ancient one giving rise to the distantly related and unlinked (3) single prolactin (PRL) gene (4, 5). The linked GH and CS genes, presumed to be generated by 3 recent duplication events, now share >90% nucleotide sequence identity. These genes are expressed in a highly tissue-specific manner; hGH-N is expressed solely in pituitary somatotropes/somatolactotropes, and the hCS and hGH-V genes are expressed exclusively in the syncytiotrophoblastic layer of the placenta (6, 7). In contrast, hPRL is expressed in both pituitary lactotropes/somatolactotropes and placental decidua (8).