Effects of oral 2,6-cis-diphenylhexamethylcyclotetrasiloxane on the reproductive system of the male Macaca mulatta.

Abstract

Abstract: An organosilicon compound, 2,6‐cis‐diphenylhexamethylcyclotetrasiloxane, cyclic 2,6‐cis‐[(PhMeSiO)2(Me2SiO)2], is a novel structure possessing estrogenic, antigonadotropic and antifertility activity in the rat. Cyclic 2,6‐cis‐[PhMeSiO)2 — (Me2SiO)2], was administered orally for 28 days to mature male rhesus monkeys to assess effects on the histology of the reproductive system and the tissue distribution of cyclosiloxane‐derived silicon. Other groups were given estradiol benzoate (0.05 mg/kg) subcutaneously for comparison. Both compounds stimulated various degrees of sexual skin edema; a known estrogen‐dependent response in the monkey. Picnotic nuclei appeared in the epithelium of the caput epididymis, at 0.1 mg/kg of the cyclosiloxane and gross tubular atrophy was evident at 10 mg/kg. Estradiol benzoate had little or no effect on these tissues. Disruption of spermatogenesis occurred at 1.0 mg/kg cyclosiloxane and above. The secretory activity of the prostate was suppressed at 10 mg/kg and above, and the epithelial cells of the seminal vesicles showed some signs of atrophy at 100 mg/kg, the highest dose tested. Estradiol benzoate suppressed the secretory activity of both sex accessory tissues. Cyclic 2,6‐cis‐[(PhMeSiO)2 (Me2SiO)2] enlarged the livers at all dose levels and decreased spleen weight at 100 mg/kg. Estradiol was without effect in this regard. The distribution of cyclosiloxane‐derived silicon was primarily to bile, fat, lymph nodes, urine, adrenals, testes, prostate, liver, pituitary, and epididymis in decreasing order of silicon concentration. The increase of silicon in the pituitary following treatment with cyclic 2,6‐cis‐[(PhMeSiO)2 (Me2SiO)2] is consistent with the proposed antigonadotropic mechanism. The data presented here have demonstrated that subacute oral dosing of the male rhesus monkey with cyclic 2,6‐cis‐[(PhMeSiO)2(Me2SiO)2] results in an antigonadotropic action generally comparable to the action of subcutaneously administered estradiol benzoate.