THE ROLE OF ESTROGEN IN THE FEEDBACK-REGULATION OF FOLLICLE-STIMULATING-HORMONE SECRETION IN THE FEMALE RAT

Letrozole (CGS 20267) is a non-steroidal aromatase inhibitor which, at its maximally effective dose of 1 mg/kg p.o., elicits endocrine effects equivalent to those seen after ovariectomy. Adult, female cyclic rats were administered letrozole (1 mg/kg p.o.) once daily for 14 days. A control group of animals was ovariectomized on day 1 of treatment and a third group of animals served as untreated controls. During the experiment, vaginal smears were taken daily and at the end of 14 days all animals were sacrificed, trunk blood was taken for serum estradiol, LH and FSH measurements and the uterus and ovaries were removed and weighed. The ovaries were then fixed and prepared for histological examination. Serum hormone measurements showed that after treatment with letrozole, serum estradiol levels were reduced by 76% of untreated controls and serum LH was elevated to 378% of control values. These compared favorably with those seen after ovariectomy, serum estradiol was reduced by 78% and serum LH was elevated to 485% of untreated controls. However, FSH was unchanged after letrozole treatment (125% of control), whereas after ovariectomy FSH rose to 398% of control. Uterine weight was suppressed in the letrozole-treated animals as well as the ovariectomized animals by 60 and 70%, respectively. The histology of the ovaries of animals treated with letrozole were consistent with the serum hormone findings. Except for the effects on serum FSH, these results confirm previous findings that treatment with letrozole elicits endocrine effects similar to those seen after ovariectomy. Furthermore, these results demonstrate that FSH secretion is not under the control of estradiol whereas LH secretion is under feedback control of ovarian estrogen.