Janice Mary Bahr
Regulation of Progesterone Biosynthesis by Androgens in the Ovary of the Domestic Hen
The ovary produces hormones called steroids. The major steroids secreted are progesterone, androgen, and estrogen. The production of these steroids is controlled by hormones from the pituitary gland. This mode of regulation is described as endocrine control. More recent studies suggest that steroids may regulate their own production at the level of the ovary. This regulation is described as paracrine control. Therefore, it appears that the production of steroids by the ovary is regulated by both endocrine and paracrine means.
The ovary of the domestic hen is an excellent model to investigate the paracrine regulation of steroids. The follicles are large and are arranged in a hierarchy so that the precise maturity of the follicle can be determined. It is also easy to obtain large numbers of the two cell types, the granulosa and theca cells, which produce steroids. As the follicle matures and approaches ovulation, there is a rapid increase in the production of progesterone and a concomitant decrease in androgen. In the ovary, cholesterol is converted into pregnenolone which is then converted into progesterone which, in turn, is converted into androgens. Therefore, an intriguing question is why the increase in progesterone occurs with a simultaneous decrease in androgen. There are two possible hypotheses to test. Professor Bahr and her team will test the hypothesis that androgens inhibit the production of progesterone by altering the activity, the amount, and/or the synthesis of the enzyme which converts cholesterol to pregnenolone. They will accomplish their goal by incubating granulosa cells, the cells that produce progesterone, with various doses of androgens and determine if there is a change in activity, amount, and/or synthesis of the rate-limiting enzyme (cytochrome P450 side chain cleavage enzyme). They will use traditional techniques as well as those of molecular biology. These proposed experiments are valuable because results obtained from these studies will extend our understanding of the regulation of steroid production by the ovary. The production of these steroids at various times in the lifetime of the female are essential for reproduction and the health of the individual.