Differential, multihormonal regulation of the mouse major urinary protein gene family in the liver.

Abstract

The hormonal requirements for the regulation of the major urinary protein (MUP) mRNA levels in mouse liver have been examined. Previous experiments have shown that administration of testosterone to female or castrated male mice increases MUP mRNA levels approximately fivefold to normal male levels. We have found that thyroxine and the peptide hormone, growth hormone, each had a pronounced effect on MUP mRNA levels. MUP mRNA was reduced 150-fold in growth-hormone-deficient mutant mice (little). The administration of growth hormone and thyroxine induced MUP mRNA approximately 150-fold, and when administered together, they induced MUP mRNA approximately 1,000-fold. testosterone administration. When administered separately to these mice, growth hormone and thyroxine induced with MUP mRNA approximately 150-fold, and when administered together, they induced MUP mRNA approximately 1,000-fold. Testicular feminized mice, which lack a functional major testosterone receptor protein, can also be induced to male levels by treatment with both growth hormone and thyroxine. In addition, we present evidence which indicates that growth hormone, thyroxine, and testosterone differentially regulate the levels of distinct MUP mRNA species.The major urinary proteins (MUPs) of mice were originally described as a group of antigenically related low-molecular-weight acidic proteins synthesized in the liver, secreted into the serum, and ultimately excreted in the urine (14-16). A homologous protein, a2.-globulin, has been described in rats (24,31,32). More recently, hybridization experiments have shown that the MUPs constitute a multigene family of 20 to 30 genes (7,18). Genetic mapping studies with recombinant inbred mice and mouse-hamster hybrid cell lines indicate that the MUP structural genes are clustered on chromosome 4 (5, 7, 20).Although the liver appears to be the major site of MUP synthesis, recent studies have shown that the MUP gene family is expressed in several secretory tissues of mice (18,34). The tissues expressing MUP mRNA sequences are the liver, the submaxillary gland, the lachrymal gland, and the mammary gland. These studies also indicated that expression of MUP mRNA in each of the tissues is under different developmental and hormonal controls (34).Early studies on the regulation of the MUPs examined the urinary levels of those proteins whose major site of synthesis appears to be the liver (36; this paper). Parfentjer (28) ed that male mice exhibit high levels of proteinuria and that the onset of this proteinuria correlated with the onset of sexual maturity. The role of the major male sex steroid, testosterone, was further indicated by demonstrating that either females or castrated males treated with testosterone attain normal male levels of proteinuria (38). Biochemical examination of these urinary proteins by Finlayson et al. (16) revealed a group of low-molecular-weight acidic proteins which exhibit both strain-and sex-specific electrophoretically distinguishable phenotypes (14, 37). Interestingly, these studies a...

The lipocalin protein family: structure and function

“…However, constitutive expression of MUP has been demonstrated in the salivary and lachrymal glands [56]. The sex-dependent expression of MUP (adult male mice secrete 5-20 times as much MUP as do females) and its ability to bind a number of odorant molecules [57] is consistent with the suggestion that MUP acts as a pheromone transporter [59] ; the protein may be excreted into the urine carrying a bound pheromone which is released as the urine dries and the protein denatures. This proposal is strongly supported by the work of Bacchini and colleagues, who have successfully purified MUP from mouse urine with bound ligands [60].…”

“…In the liver, expression of MUP is stimulated by androgens, principally testosterone, and is modulated by thyroxine and peptide growth hormones : addition of thyroxine or growth factors in the presence of testosterone increases MUP expression 150-fold [57]. However, constitutive expression of MUP has been demonstrated in the salivary and lachrymal glands [56].…”

The effects of graded levels of calorie restriction: IX. Global metabolomic screen reveals modulation of carnitines, sphingolipids and bile acids in the liver of C57BL/6 mice

“…This result is likely to be unique to male mice, as they produce significantly more MUPs in their urine than female mice, which are stimulated by testosterone, growth hormone and thyroxine (Knopf et al ., 1983). MUPs were also negatively correlated with S1P, sphingomyelin and L‐carnitine.…”

Reintroducing domesticated wild mice to sociality induces adaptive transgenerational effects on MUP expression

“…Testosterone contributes to male sexual characteristics such as social status (25), attractiveness to females (26), and pheromones, including MUPs (27). Testosterone is also involved in tradeoffs with life-history characteristics, including decreased survival (25).…”