Only a limited amount of information is currently available on the control of follicle growth and follicle atresia. Many clinical situations in the human that result in excessive androgen secretion are associated with ovulatory failure. Recent work in our laboratory has used an animal model for the study of follicular atresia. The model consists of injecting 32 IU of pregnant mare serum gonadotropin (PMSG) on Day 30 to female rats hypophysectomized on Day 24 and studying either ovarian histology for various healthy and atretic follicular counts or ovulation induced by hCG 54 hrs after the PMSG. This model which gives near normal ovulation and in which the histological findings can be confirmed by a functional response, was used to demonstrate that the non-aromatizable androgen DHT caused follicular atresia and that estradiol was protective against the DHT effects. The renewal proposal will study the time course of the effect of DHT in altering blood and ovarian steroids, granulosa cell and whole ovary steroidogenesis, particularly, 5 Alpha-reductase and aromatase and granulosa cell FSH and LH receptors. Attempts will be made to separate healthy and atretic granulosa cells using Percoll and metrizamide gradients. Since a single injection of DHT results in elevation of blood steroids for only short periods of time, the above will also be studied in the presence of a stable blood level of DHT achieved by implanting a Silastic capsule of DHT. The effects of DHT on altering estrogen effects in increasing FSH sensitivity and development of granulosa cel LH receptors will be studied by using increasing quantities of DHT in the presence of a constant amount of estradiol in the hypox rat. The role of androgens and estrogens in the regulation of follicular growth and atresia will be further studied in the hypox rat and in the young adult cycling rat by the use of anti-androgens ad antiestrogens and examination of granulosa androgen and estrogen receptor dynamics. The results will not only provide new information on the control of mammalian folliculogenesis but may also be of value in understanding human polycystic ovarian disease.
| Mahesh, Virendra B (2012) Hirsutism, virilism, polycystic ovarian disease, and the steroid-gonadotropin-feedback system: a career retrospective. Am J Physiol Endocrinol Metab 302:E4-E18 |
| Mahesh, V B; Mills, T M; Bagnell, C A et al. (1987) Animal models for study of polycystic ovaries and ovarian atresia. Adv Exp Med Biol 219:237-57 |
