Divergence between ovarian aromatase activity, estrogen, and androgen levels in the cycling rat

Serum estrogen levels vary in a cyclic fashion during the rat estrous cycle, reaching peak values on proestrus and then rapidly declining. Daily measurements of ovarian aromatase activity appear to follow a similar pattern, suggesting a potential regulatory role for the enzyme. To examine this hypothesis, mature rats were killed at various times, and ovarian microsomes were assayed for aromatase activity, while androstenedione, testosterone, estradiol, and estrone levels were measured in ovarian cytosol by RIA. The ovarian aromatase activity reached a peak about 9 h after the onset of the light period on the day of proestrus, and then began to decrease gradually to 75% lower levels by the morning of estrus. Similarly, the estradiol levels also peaked at about 9 h, but then dropped sharply; at 18 h the estradiol levels were reduced 90-95%, while aromatase activity was still close to its peak value. In contrast, the androstenedione and testosterone levels remained high for 3-4 h after the estradiol levels began to decrease. Estrone levels varied considerably less than those of estradiol, reaching lower peak values, but then decreasing only 50-75%. The dissociation between product levels and enzyme activity cannot be explained by a change in the Km of aromatase, which was about 20 nM for androstenedione throughout this period. Therefore, it appears that the decrease in estradiol levels from the peak of the surge may in part be a consequence of a shift in the ratio of the estrogen products synthesized by the ovary, rather than a decrease in the ovarian capacity for estrogen production, although other factors appear to be involved as well.