Because androgenic hormones produce an increase in kidney size and the production of kidney glycosphingolipids and because the level of tissue glucosylceramide (GlcCer) has been implicated as a modulator of organ size, we measured the activities of two enzymes in mouse kidney that (in part) determine the level of this glycolipid. GlcCer synthase was found to rise in specific activity with age and increased kidney size, whereas GlcCer glucosidase was found to decrease with age; both enzyme changes act to elevate the level of kidney GlcCer and point to the level of this lipid as a determinant of kidney size. The increase in synthase was especially rapid in male kidney, consistent with the more rapid growth of male kidney. Testosterone injection into both males and females produced elevated levels of GlcCer synthase, decreased levels of the hydrolase, and more rapid growth. Injection of 17 beta-estradiol, which produced slow or negative kidney growth, caused the synthase activity to decrease in female mouse kidney and the glucosidase activity to rise in both sexes. Thus the changes in kidney size produced by the two hormones paralleled the changes in GlcCer level predicted by the hormone effects on the two enzymes. In liver, estradiol produced increases in both enzymes but only the male liver increased in size. Testosterone did not affect the liver. The testes grew with age but the activities of both enzymes decreased.
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