Mechanisms contributing to the sex difference in levels of granulocyte-macrophage colony-stimulating factor in the urine of GM-CSF transgenic mice.

Levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) were 30- to 40-fold higher in the urine of male GM-CSF transgenic mice than in female transgenic mice, despite uniform elevations in both sexes of serum GM-CSF levels. Male transgenic bladder tissue produced two to four times more GM-CSF in vitro than female transgenic or control bladder tissue, but no sex differences were observed in the production of GM-CSF in vitro by kidney tissue. No sex differences were observed in the serum half-lives of native or recombinant GM-CSF in C57BL or littermate control mice, and the half-lives of recombinant GM-CSF were shorter than those of native GM-CSF. The studies indicated that some GM-CSF in urine can represent plasma GM-CSF cleared by the kidney, and native GM-CSF was cleared to the urine more efficiently than recombinant GM-CSF. Female transgenic mice exhibited a subnormal capacity to clear injected native GM-CSF to the urine. Although granulomas were present in the bladder wall of some transgenic mice, their presence did not correlate with the GM-CSF levels in the urine.