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Effect of Diethylstilbestrol on Ovarian Responses to Pregnant Mare's Serum Gonadotropin in Hypophysectomized Immature Rats^*

Departments of Gynecology and Obstetrics and Physiology, Ralph L. Smith Research Center, University of Kansas Medical Center Kansas City, Kansas 66103

Requests for reprints should be addressed to: Dr. Donald C. Johnson, University of Kansas Medical Center, College of Health Sciences and Hospital, Department of ObG, Rainbow Boulevard at 39th, Kansas City, Kansas 66103.

Abstract

The temporal relationships between changes in ovarian cAMP content, ornithine decarboxylase activity (ODC), as well as serum sex steroid concentrations were studied in immature hypophysectomized rats treated with either diethylstilbestrol (DES) or sesame oil 72 h before an iv injection of 20 IU PMS gonadotropin (PMSG). The DES treatment produced about a 50% increase in ovarian weight over that of controls; this increase was largely due to an increased number of granulosa cells in preantral follicles. The rate of ovarian weight increase after injection of PMSG was greater in DES-treated animals than in controls, and was more pronounced after 48 h when luteinization was evident in ovaries exposed to DES.

DES did not alter quantitatively or temporarily the changes in ovarian cAMP content induced by PMSG. Changes in ovarian ODC were also similar in oil- or DES-treated animals during the first 12 h after PMSG. Ovaries exposed to DES showed a significant secondary rise in ODC which was not found in controls. At 48 h after PMSG, the ovarian ODC level was the same in oiland DES-treated animals.

Peak levels of serum progesterone were found at 12 h in DES-treated and control animals, after injection of PMSG and then progesterone concentration began to decrease in the serum of controls. Animals given DES also showed a drop in serum progesterone between the 12th and 18th h, but in contrast to the controls, they showed a rapid increase after 18 h to levels much higher than those found at 12 h. This secondary rise was correlated with the appearance of luteinized granulosa cells. Unlike progesterone, serum testosterone and estradiol levels did not increase significantly during the first 12 h after injection of PMSG, but concentrations of these hormones were increased in animals killed at later times. Animals pretreated with DES had higher levels of serum testosterone and estradiol at 24 h and at later times than did controls.

The results indicate that granulosa cells induced to mitogenic activity by DES give many of the same responses to gonadotropin as do normal granulosa cells from immature ovaries. However, DES pretreatment alters the granulosa cell so that luteinization occurs by about 60 h after exposure to PMSG. This effect of estrogen is manifested earlier by an increase in the production of progesterone. (Endocrinology 102: 1563, 1978)

Footnotes

^* This work was supported in part by a grant from the National Cancer Institute.

Received April 25, 1977.