Effects of the Androgen Antagonist Cyproterone Acetate on the Testicular Structure, Spermatogenesis and Accessory Sexual Glands of Testosterone-Treated Adult Hypophysectomized Rats

Abstract

SUMMARY The antagonistic action of 1,2α-methylene-6-chloro-Δ4,6-pregnadiene-17α-ol-3,20-dione-17α-acetate (cyproterone acetate) to testosterone propionate (TP) on the testes and accessory glands was investigated in hypophysectomized adult male rats. Treatment of the animals began on the day of hypophysectomy and was continued for 21 days. Daily subcutaneous injections of 0·3 or 1·5 mg. TP/100 g. body weight almost completely inhibited testicular atrophy and involution of the germinal epithelium. Simultaneous administration of 0·3 mg. oestradiol/100 g. body weight did not influence the effect of testosterone propionate. Cyproterone acetate inhibited the effect of testosterone propionate. The extent of inhibition was dose dependent. The antagonism to testosterone was manifested by reduction of testicular weight and by the inhibition of spermiogenesis. The latest stages of spermiogenesis were primarily influenced. Intratesticular cyproterone acetate together with subcutaneous administration of TP caused similar effects in the testes to those of subcutaneous administration. However, regression of the germinal epithelium in the injected testis seemed to be more pronounced than in the contralateral testis. The effects of TP on the accessory sex glands (prostate, seminal vesicles) were inhibited by simultaneous administration of cyproterone acetate. It is concluded that cyproterone acetate competitively inhibits the action of testosterone propionate on the target organs.

Dihydrotestosterone Inhibits Interleukin-1.ALPHA. or Tumor Necrosis Factor .ALPHA.-Induced Proinflammatory Cytokine Production via Androgen Receptor-Dependent Inhibition of Nuclear Factor-.KAPPA.B Activation in Rheumatoid Fibroblast-Like Synovial Cell Line

“…It is reported that the IL-8 gene activation is regulated by NF-kB, C/EBP and AP-1, each of them alone or in synergy, depending on cell type. 23) In MH7A cells the NF-kB binding site in the promoter region of the IL-8 gene appeared to be critical for the IL-1a or TNFa-induced transactivation of the gene. This was confirmed by the observation that NF-kB, ei- ther IL-8 gene-or Ig-kB-derived, was markedly activated by IL-1a or TNFa, while C/EBP and AP-1 were not at all or only slightly activated.…”

Male pseudohermaphroditism due to 17α-hydroxylase deficiency

“…Miullerian duct suppression, while there were varying degrees of incomplete Wolffian development, phallic growth, and labioscrotal and urethral development. There is ample evidence to support the theory of Jost (22)(23)(24) that the testis plays an inducer role in the Miillerian suppression and that this inducer is not testosterone (25). Further, the development of the Wolifian system apparently requires both inducer substance and androgen while external genitalia are largely dependent on androgen.…”

Dihydrotestosterone Inhibits Tumor Necrosis Factor .ALPHA. Induced Interleukin-1.ALPHA. mRNA Expression in Rheumatoid Fibroblast-Like Synovial Cells

“…To determine whether the inhibitory effect of DHT was mediated by AR, MH7A cells were treated with TNFa with or without DHT in the presence or absence of androgen receptor antago- nist, hydroxyflutamide (OHF). 21) As shown in Fig. 2B, OHF significantly reversed the inhibitory effect of DHT.…”