Effect of a non-steroidal antiandrogen, flutamide, on the hypothalamo-pituitary axis, genital tract and testis in growing male rats: endocrinological and histological data

Abstract

Abstract. Male Wistar rats were treated between 23 to 38 days of age with flutamide. Hypothalamic LRH content, pituitary gonadotrophin concentrations and plasma LH, FSH, Prl and testosterone levels were measured by radioimmunoassay. The testis, epididymis and accessory organs were weighed and the histology of the testis, and the estimation of gonadotrophin receptors were performed in the same animals. The results were compared with data obtained in control animals of the same age. Flutamide treatment induced a direct inhibition of the genital tract. On the hypothalamo-pituitary axis, flutamide acted as a pure antiandrogen able to inhibit the negative feedback of testosterone, producing an increase in pituitary LH synthesis, as well as release of LH, FSH and Prl. The high level of plasma LH stimulated hyperplasia and hypertrophy of interstitial cells of the testis. Consequently testosterone synthesis was stimulated, although the number of LH receptor sites per Leydig cell was unchanged. Sertoli cells divisions were stimulated by the high level of gonadotrophins, but Sertoli cell function and the number of FSH receptors sites per Sertoli cell were slightly decreased. The increase in the number of type A spermatogonia and early stages of meiosis of primary spermatocytes could be related to the increase in plasma levels of FSH, whereas the drastic decrease in the late stages of spermatogenesis could result from the direct inhibition of testosterone by flutamide in the seminiferous tubules.