The human growth hormone (hGH)-prolactin (hPRL) gene family includes at least 5 active genes responsible for critical controls over growth and reproductive development. The GH-related genes are considered to promote linear body growth and are referred to as somatogenic, while the Prl-related genes function primarily in reproduction and lactation and are referred to as lactogenic. The known major sites for the expression of these somatogenic and lactogenic hormone genes are the pituitary and/or the placenta. The structural basis for the specific spectrum of each hormone's bioactivity is unknown. Recent evidence from this laboratory has suggested an unexpected level of complexity in this gene family. The hGH-variant (hGH-V), previously a poorly-defined member of the GH gene cluster, was shown to be expressed at significant levels in the placenta. In addition, hGH-V was shown to encode two discrete mRNAs each of which may encode a distinct protein product. Further data from this laboratory suggests that a number of hPrl- related genes may also be expressed in the placenta.
The specific aims of the present proposal are to: (1) fully characterize the expression of the hGH-V gene in the human placenta, (2) map the functional domains within the GH-Prl proteins, (3) characterize the alternative splicing patterns of the somatogenic and lactogenic gene transcripts, (4) identify and characterize additional members of the lactogenic-somatogenic family of genes expressed in the human placenta, and (5) determine the genetic controls which specify the expression of these genes in the placenta. The expression of these genes will be studied in primary placental tissue in cell lines derived from placental tissue, and in stable transfected cell lines expressing either the native genes or gene chimeras constructed by recombining segments of pairs of genes from the somatogenic-lactogenic gene family. The expression of these genes, the structures of the processed mRNAs, and the functions of their encoded proteins will be defined by a number of biochemical assays of DNA, mRNA, and protein structure and function. The long- term goals of this work are to fully define the members of the somatogenic-lactogenic gene family, the genetic controls over their function, the biochemical basis for the complexity of their gene and protein function, and the relationship between their expression and the normal functions of the placenta in fetal growth and development.
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