Alternative Processing of Growth Hormone Receptor Transcripts*

H RECEPTOR (GHR) is a transmembrane protein that binds GH with high affinity and specificity. Expres- sion of the receptor is a requirement for cellular responsive- ness to GH. The primary transcript that generates the GHR mRNA can undergo alternative processing to produce sev- eral related mRNAs, including transcripts that encode the circulating GH-binding protein (GHBP) and a truncated GHR that inhibits normal cellular responses to GH in vitro. In addition, the use of alternative promoters and transcrip- tion start sites in the GHR gene-regulatory region generates transcript forms that differ only in the 59-untranslated region (59-UTR). This article will review the transcripts originating from the GHR gene. The introduction will address the ex- pression of GHR and GHBP, the major transcripts of the gene. The second section describes the structure of the GHR gene. The third section describes the types of alternative transcripts produced by the gene, the alternative processing mechanisms that produce them, and the biological functions of their protein products. The final section suggests future studies on the expression and function of alternative GHR transcripts. Normal postnatal growth in mammals requires the pres- ence of GH, a Mr 22,000 polypeptide hormone released pri- marily from the anterior pituitary gland (reviewed in Ref. 1). GH is bound with high affinity and high specificity by two proteins, the GHR and GHBP. The receptor is associated with the cell membrane of GH target tissues and mediates the somatogenic and metabolic effects of the hormone. The bind- ing protein is found in the serum and forms complexes with circulating GH. Although the exact biological role of the binding protein has not yet been determined, it has been shown to enhance the growth-promoting effects of GH in vivo (2, 3), probably by increasing the half-life of GH in the cir- culation (4).