SEXUAL DIMORPHISM AND GROWTH-HORMONE INDUCTION OF MURINE PHEROMONE-BINDING PROTEINS

A number of structurally very similar pheromone-binding proteins (majo r urinary proteins; MUPs) are synthesized in mouse liver and rapidly e xcreted in the urine. Male and female inbred mice display different ch aracteristic patterns of MUP expression. Here we present a detailed st udy of the RNA and protein products corresponding to specific MUP gene s previously isolated from genomic DNA of the Balb/c strain. By in vit ro transcription of equivalent cDNA clones, translation of the resulti ng RNA in the reticulocyte lysate system and isoelectric focusing, the protein products of genes BL1, BS1 and BS6 were shown to be MUP 2a, M UP 2b and MUP 4 respectively. MUPs 2a and 2b were shown to be abundant both in Balb/c male urine and translation products of total Balb/c ma le liver mRNA. Two oligodeoxynucleotide probes, oBL1A and oBS1, select ive for BL1 and BS1 mRNA respectively, were chemically synthesized. mR NA that hybridized with these probes (oBL1A mRNA and oBS1 mRNA) was pr esent at different characteristic levels in the Balb/c and C57BL/6 inb red strains. In both strains the level of expression was much higher i n males than females and the male/female expression ratio of oBS1 RNA was higher than that of oBL1A RNA. Comparison of these mRNA levels wit h the amounts of different MUP proteins present in urine and the trans lation products of liver mRNA indicated that proteins other than MUP 2 a and MUP 2b are coded for by the C57BL/6 oBL1A and oBS1 mRNAs. C57BL/ 6 mice homozygous for the lit mutation are GH deficient and transcribe MUP genes at a level much lower than that obtaining in normal mice of either sex, indicating that transcription is induced by GH in both ma les and females. When lit/lit mice were treated with GH under two diff erent regimes, MUP gene transcription was partially induced to differe nt degrees and the level of oBL1A mRNA was induced more highly than th at of oBS1 mRNA. Thus there exists a correlation between the inducibil ity of these mRNAs and their level of expression in females relative t o males; oBL1A mRNA is both more highly expressed in females and more readily induced by GH than oBS1 mRNA. This suggests that the male and female expression patterns are due to differential inducibility of dif ferent MUP genes together with a stronger inducing stimulus in males. GH administered continuously by infusion repressed MUP gene expression . We interpret this to mean that induction is due to intermittent GH s timulation in both sexes and that the longer interpulse interval repor ted to occur in males leads to more effective induction than the short er interpulse interval observed in females.