The atrophic effects of a synthetic steroidal anti-
androgen,
TZP-4238, on the pituitary, prostate and adrenal gland of rats were investigated. Male Sprague-Dawley rats were divided into three experimental groups. Group 1 consisted of controls. Groups 2 and 3 received
chlormadinone acetate (CMA) 50 mg/kg/day and
TZP-4238 10 mg/kg/day p.o., respectively, for 3 weeks. CMA (Group 2) produced marked
atrophy of the prostate. Furthermore, CMA caused marked
atrophy of the adrenal gland. Histopathologically, the remarkable
atrophy was observed in the adrenal cortical cells of zonae fasciculata and reticularis. The most striking ultrastructural alterations were noted in the mitochondria. In addition, intramitochondrial localization of
glutathione-peroxidase (GSH-PO) which effectively reduces the
lipid peroxides, was less than that in the controls. In the anterior pituitary gland, CMA induced a reduction in the size of
ACTH cells.
TZP-4238 (Group 3) produced marked
atrophy of the prostate. However,
TZP-4238 exerted no effect on the adrenal gland or anterior pituitary
ACTH cells. In addition, the present histopathological study showed that
TZP-4238 or CMA exerted no effect on the testes or anterior pituitary LH cells. Therefore, it is suggested that
TZP-4238 causes
atrophy of the prostate without any significant histopathological changes in the adrenal glands or anterior pituitary
ACTH cells under the present experimental conditions. We further speculated that
TZP-4238 had a more potent anti-prostatic effect than CMA and
TZP-4238 had a less inhibitory influence than CMA on the pituitary-adrenal axis.