Chronic treatment of intact male beagles with an orally active nonsteroidal aromatase inhibitor (4-(5,6,7,8-tetrahydroimidazo [1,5a] pyridin-5-yl) benzonitrile hydrochloride; CGS 16949; CIBA-GEIGY) at a dosage of 2.5 mg./kg. per day for six months resulted in increased (p < 0.01) serum LH and testosterone concentrations compared to placebo-fed controls. The increases in serum LH and testosterone concentrations occurred by one week of treatment and were maintained over the six month period. Testes of CGS 16949A fed dogs obtained at termination of the experiment when perfused in vitro in the presence of a maximally stimulating concentration on LH secreted nondetectable amounts of estradiol and estrone and higher (p < 0.01) amounts of testosterone, androstenedione and dihydrotestosterone than testes of control dogs. Despite these changes in androgen secretion there was no evidence of any effect of aromatase inhibition upon spermatogenesis. These data support the hypothesis that in the dog, estrogens play a major role in negative feedback of the hypothalamic-pituitary-testicular axis.
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