HORMONAL-REGULATION OF ALDOSE REDUCTASE IN RAT OVARY DURING THE ESTROUS-CYCLE

The physiological roles of aldose reductase [alditol:NAD(P)(+) 1-oxido reductase] have not been fully elucidated yet, although it has been im plicated in the pathogenesis of diabetic complications. In the rat ova ry we found remarkable changes in the enzyme level during the 4-day es trous cycle. After diestrus, the activity and protein content of aldos e reductase increased to the maximum level on proestrous morning and r apidly fell off to the lowest level on the early morning of estrus. At this time its mRNA level in the ovary was significantly decreased com pared with that on the morning of proestrus. Immunohistochemical stain ing of the diestrous ovary demonstrated localization of the enzyme pro tein in the granulosa cells and in the oocytes. At the end of proestru s when its level was low, immunoreactive aldose reductase in the granu losa cells was localized preferentially to the antrum side, with lesse r staining in the cells lining the follicles. Administration of chlorp romazine to the rats on proestrus significantly restored the enzyme le vel on the following morning of the expected estrus. This effect of ch lorpromazine was abolished when human chorionic gonadotropin was admin istered to the chlorpromazine-treated rats. When chlorpromazine was ad ministered to the rats treated with bromocriptine, an inhibitor of pit uitary prolactin secretion, aldose reductase activity in the ovary was significantly elevated compared with that in the rats treated with ch lorpromazine alone. These findings suggest that in the rat ovary it is under hormonal regulation during the estrous cycle. The enzyme may po ssess a new functional role in the reproductive system of the female r at, which can be disordered under diabetic conditions.