THE DIFFERENTIAL MECHANISMS BY WHICH PICROTOXIN AND COPPER ACETATE INDUCE OVULATION IN THE RABBIT

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Abstract
Copper salts and convulsant drugs such as picrotoxin induce ovulation in the rabbit by stimulating LH release from the adenohypophysis. It has been generally agreed that the chemical agents exert their effect on the central nervous system and that activation of the hypophysis is indirect. The present study, which employs 150 mature female rabbits, introduces evidence that, whereas picrotoxin definitely functions by way of the nervous system, at least a large part of the copper stimulus is exerted directly on hypophyseal cells. Picrotoxin-induced ovulation was always preceded by convulsions; in their absence pituitary activation failed to occur. Reduced dosages of picrotoxin led to extremely severe convulsions in rabbits previously treated with Dibenamine or atropine, but ovulation followed in only one case in 10 animals so treated. These results are interpreted as evidence that the nervous stimulus was generally blocked from reaching the hypophysis. Nembutal in anesthetic doses blocked the convulsive and pituitary-stimulating actions of doses of picrotoxin 2-4 times the minimal stimulating level. Ovulation was induced by copper acetate in dosage which produced no overt signs of nervous stimulation. The copper stimulus to ovulation was blocked by neither the antiadrenergic, the anti-cholinergic nor the anticonvulsive agent. Finally, pituitary activation was achieved by injecting tiny amts. of copper acetate directly into the adenohypophysis. Preliminary treatment with estrogen facilitates both neurogenically and copper-induced ovulation. It is suggested that the steroid acts at the hypophyseal level by lowering thresholds to both neurohumoral and direct chemical stimulation.