Polyhydric alcohols, or polyols, are osmotically active organic molecules whose physiologic and pathophysiologic significance has only very recently come under investigation. These molecules are produced by the reduction of common sugars via the catalytic action of aldose reductase. It appears that the overproduction and accumulation of polyols such as sorbitol, the product of glucose reduction, in certain tissues, may be responsible for some of the dire consequences of chronic hyperglycemia, as in diabetes mellitus or hereditary galactosemia. In the later disease, females suffer from premature ovarian failure due to the depletion of ovarian follicles, while reproductive function in males is not affected. We have described the cellular localization of aldose reductase mRNA in the granulosa cells of the rat ovary and interstitial cells of the testis. We showed that feeding gravid and lactating rats a 50% galactose diet resulted in a 60% reduction in ovarian follicle number in the female offspring, but no apparent abnormality in male gonads. This decline in follicle number was not prevented by the simultaneous administration of an aldose reductase inhibitor, which prevented polyol accumulation. We conclude that the premature ovarian failure associated with galactosemia is not caused by polyol accumulation in the ovary, and suggest that aldose reductase has a role in steroid synthesis in the gonad.
