Hormonally regulated sequences in mouse kidney, liver, and rat HTC cells are being studied to answer basic questions related to the mechanisms of hormone action. These include questions pertaining to: (1) tissue specifcity, (2) gene structure, and (3) possible alterations in gene expression at the transcriptional, post-transcriptional, translational, or post-translation level. An abundant androgen-regulated mRNA in the mouse kidney (KAP) has been identified. Hybridization studies indicate KAP mRNA is present in lower levels in females and castrated males than normal males and does not appear to be expressed to any extent in other mouse tissues. A comparison of in vitro and in vivo synthesized mouse kidney proteins suggests that the KAP protein may be regulated at the translational level. The major urinary proteins (MUPs) are a family of proteins synthesized in the liver, secreted, and ultimately excreted. Studies have shown these proteins to be hormonally regulated, males having higher levels than females. Since androgens exert a profound effect on biosynthesis and secretion of the MUPs, we have been investigating biosynthesis of the MUPs at the translational level. Results indicate the different MUPs are synthesized from different mRNAs as a precursor which contains an N-terminal signal sequence. In addition, growth hormone was found to have a major role in regulation of these proteins. Two abundant glucocorticoid-regulated-secretory glycoproteins synthesized by rat HTC cells are also being studied. Their glycosylation in vitro has been studied and a number of intermediate glycosylated precursor forms identified. One of these proteins is apparently hormonally regulated in tissue culture cells, tumor cells grown in the rat, as well as normal liver tissue.
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