Title

Aromatase and the biochemical regulation of rat ovarian estradiol production

Date of Award

1989

Availability

Article

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Biochemistry and Molecular Biology

First Committee Member

J. David Puett, Committee Chair

Abstract

The levels of the important regulatory hormone estradiol vary during the rat estrous cycle, reaching a peak on the day of proestrus and then rapidly falling. It has been thought that the estrogen levels increased as a consequence of proliferating ovarian granulosa cells and increased levels of aromatase, the enzyme that converts androgens to estrogens. However, ovarian aromatase activity had not been directly measured in the rat estrous cycle. These studies were undertaken to measure aromatase activity during the cycle in Sprague-Dawley rats, and to examine the cause of the rapid decrease in estradiol. Measurement of ovarian microsomal aromatase activity revealed a peak on the day of proestrus followed by a fall to 4-fold lower levels by the next day. Further studies, however, indicated that the ovarian estradiol levels decreased sharply while aromatase activity remained high. The ovarian androgen substrate concentration, as well as estrone levels, also remained high for several hours after the estradiol levels declined. Thus the levels of estradiol alone decrease at the termination of the estradiol surge, while aromatase, androgen and estrone levels decrease considerably more slowly. ln the course of these studies it was observed that the maximal proestrus aromatase activity varied significantly during the year, with a peak in summer and a nadir in winter, but neither androgen nor estrogen peak levels showed any circannual variation. In order to examine the role of aromatase activity in maintaining estrogen levels, the aromatase inhibitor 10-propargylestr-4-ene-3,17-dione was administered to rats, and ovarian aromatase activity and steroid levels were measured. A 60% inhibition of aromatase resulted in greater than 40% lowering of both ovarian estrogens. On the other hand, the estrogens recovered to control values even with continued inhibition of aromatase. Therefore, while aromatase may play a facilatory role in estrogen synthesis, clearly other regulatory factors must be involved in maintaining and limiting the rat proestrus estrogen surge.

Keywords

Chemistry, Biochemistry

Link to Full Text

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