Ovarian Steroidogenesis in the Brown Norway Rat with Age.

The Brown Norway rat has been shown to be an excellent model of male reproductive aging. This is due in part to the low incidence of morbidity in the strain with age. In addition, the decrease in testosterone production in the male rat with age appears to occur in a manner similar to that observed in man. Based on these assumptions, we developed a study to examine ovarian aging in the female Brown Norway rat. Female Brown Norway rats were obtained at 5 (young) and 24 (old) months of age. Vaginal smears were obtained to determine the stage of the estrous cycle prior to collection of blood and ovaries. All collections were performed on the morning of estrus. One ovary from each animal was fixed with a modified Bouins' solution and embedded in paraffin. Sections were cut and stained with hematoxylin and eosin. The contralateral ovary from each animal was placed in culture for 4 hours, after which media were collected. Media and serum samples were analyzed by radioimmunoassay for progesterone, testosterone, and estradiol. Old animals produced significantly more progesterone and testosterone both in vivo (progesterone: old - 48.2ng/ml, young - 16.7ng/ml, p=0.017; testosterone: old - 1.0ng/ml, young - 0.6ng/ml, p=0.004) and in vitro (progesterone: old - 48.2ng/ml, young - 16.7ng/ml, p<0.001; testosterone: old - 0.48ng/ml, young - 0.21ng/ml, p<0.001) than young animals. Conversely, old animals produced significantly less estradiol both in vivo (old - 10.8pg/ml, young - 15.4pg/ml, p=0.04) and in vitro (old - 19.7pg/ml, young - 58.6pg/ml, p<0.05) compared to young animals. Progesterone and testosterone concentrations were positively correlated (p<0.05) in the serum of both young and old animals. These data correspond to a model of chemically-induced ovarian failure in the mouse and epidemiological data of aging women. These findings suggest that the Brown Norway rat may be an excellent model for female reproductive senescence. (The views expressed do not necessarily represent the views of the Food and Drug Administration or the United States government.)

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