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Increased Plasma Corticosterone and Decreased Plasma Thyroid-stimulating Hormone Levels in Rats Treated with Vincristine¹

Department of Pharmacology, 2nd Faculty of Medicine, University of Naples, Sergio Pansini 5 80131 Naples [L. A., G. F. D., G. S., P. P.], and Department of Pharmacology, School of Medicine, University of Catania, Andrea Doria 6, 95100 Catania, Italy [U. S.]

A single i.p. injection of vincristine (1000 µg/kg) into rats increased the plasma concentration of corticosterone after a latent period of 4 hr; the effect lasted for 48 hr. The response was dose related with the threshold dose being 100 µg/kg and the maximal effect occurring after 250 µg/kg. Vincristine also increased plasma corticosterone levels in hypophysectomized rats, suggesting that the drug may have a direct action on the adrenal gland. The injection of 500 or 1000 µg/kg also reduced the plasma concentration of thyroid-stimulating hormone. Twelve and 18 hr after the injection of vincristine (1000 µg/kg), the plasma concentration of thyroid-stimulating hormone was reduced, whereas the hypothalamic content of norepinephrine, a neurotransmitter involved in the regulation of thyrotropin-releasing hormone-thyroid-stimulating hormone secretion, remained unchanged.

The adrenocortical stimulation produced by vincristine may play some role in the antineoplastic effects of this drug.

¹ This study was supported by Grant CT 75.01231.04 from the Italian National Council.

Received 10/ 6/76. Accepted 5/ 6/77.