TALAMANTES, Frank; ORTIZ, Rudy: Structure and Regulation of Expression of The Mouse Growth Hormone Binding Protein

The growth hormone binding protein (GHBP) in the mouse consists of a ligand-binding domain, which is identical to the extracellular portion of the growth hormone receptor (GHR) and a hydrophilic carboxyl terminal domain, in place of the transmembrane and intracellular domains of the GHR. The two proteins are encoded by separate mRNAs which are derived from a single gene by alternative splicing. Determination of the gestational profiles of GHR and BHBP mRNA expression in mouse liver and placenta show that in the liver, the 1.4-kilobase (kb) mRNA corresponding to the mGHBP increases approximately 20 fold between pregnant and late pregnant mice, whereas the relative increase in the expression of the 4.2-kb mGHR was 8-fold. The rise in the steady state-state levels of both mRNAs began on day 9 of gestation. MGHBP mRNA levels continue to rise until day 15 of pregnancy, while GHR mRNA abundance reaches a plateau by day 13. Serum GHBPconcentrations during the last half of gestation reflects the change in mRNA levels. By elucidating the temporal changes in GHR and GHBP mRNA abundance during pregnancy and lactation in multiple maternal tissues and by assessing the ontogeny of these mRNAs in fetal and early postnatal mouse mouse liver, we have deomonstrated that the alternastive splicing of mouse GHR/GHBP mRNA precursor is regulated in a tissue,developmental stage-and physiological state-specifc manner. In vitro studies using hepatocytes in culture have begun to elucidate the hormonal factor(s) involved in the the gestation control of the expression of the GHR and GHBP.Factors regulating expression of the mGHBP will be discussed.