EXPRESSION AND DISTRIBUTION OF MESSENGER RIBONUCLEIC-ACIDS FOR GROWTH-HORMONE (GH) RECEPTOR AND GH-BINDING PROTEIN IN MICE DURING PREGNANCY

The GH-binding protein (GHBP) in rodents consists of a ligand-binding domain, which is identical to the extracellular portion of the GH 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 messenger RNAs (mRNAs), which are believed to be derived from a single gene by alternative splicing. In the present study, we report the gestational profiles of mouse GHR (mGHR) and mGHBP mRNAs in adipose tissue, brain, heart, kidney, liver, lung, mammary gland, muscle, ovary, and pituitary and describe the ontogeny of both messages in the liver of late gestational fetuses and newborns. A ribonuclease protection assay was used to simultaneously detect the two transcripts with an antisense RNA probe complementary to the extracellular domain- and hydrophilic tail-encoding regions of the mRNAs. Levels of hepatic GHR and GHBP mRNAs increased with fetal age. In the maternal liver, the abundance of both messages increased during pregnancy, with GHR mRNA levels rising less than GHBP mRNA. Also, the ratio between the two messages in this tissue increased during pregnancy in favor of mGHBP mRNA. In maternal mammary tissue, however, expression levels of both transcripts decreased gradually throughout pregnancy starting on day 8 of gestation and declining further during lactation, reaching a minimum 7-fold reduction on day 6 of lactation relative to nonpregnant values. Although there were no pregnancy-related changes in the remaining tissues we examined, the ratio of the abundance of GHR mRNA to that of GHBP mRNA varied tissue specifically. In the maternal brain, heart, liver, and mammary gland, mGHBP mRNA levels were higher than mGHR mRNA levels. In the maternal muscle and adipose tissue, the abundance of the two mRNA species was comparable. These observations indicate a gestational, developmental, and tissue-specific regulation of the expression of mGHR and mGHBP species.