The antigonadotropic activity of an organosiloxane in the male rat: 2,6-cis-diphenylhexamethylcyclotetrasiloxane

Abstract: An organosilicon compound, 2,6‐ cis ‐diphenylhexamethylcyclotetrasiloxane, was investigated as an orally active estrogenic antigonadotropin in the male rat and compared to subcutaneously administered estradiol benzoate. The cyclosiloxane lowered serum LH and FSH in association with sex accessory tissue atrophy. Serum LH declined to 50% of the control level within 5 hrs. of a single dose of the cyclosiloxane; FSH declined more slowly. Gonadotropin levels were further decreased to 15–20% of the control level after one week of treatment. A direct anterior pituitary block was demonstrated in LRH challenged animals 8 hrs. after a single dose of the cyclosiloxane; estradiol blocked the pituitary as early as 1 hr. after estrogen administration. The cyclosiloxane decreased available releasing hormone activity at 24 hrs. This action was associated with an increase in the median eminence content of dopamine and an in vivo decrease in the rate of synthesis of dopamine from 14 C‐tyrosine. Estradiol had a similar but weaker effect. On the basis of these data it was postulated that this unusual nonsteroid structure exerts its effects at the level of the anterior pituitary and on the hypothalamus.