Suppression of Pituitary Tumor Growth and Function by Ergot Alkaloids

Summary

The in vivo and in vitro effects of ergot derivatives on prolactin and growth hormone biosynthesis in the rat have been studied. Injection with 0.05 or 0.2 mg ergotamine tartrate had no effect on in vitro prolactin synthesis by the pituitary gland. Ergocornine and ergocryptine, however, inhibited both synthesis and release of prolactin. Incubation of glands with 4 or 40 µm ergotamine greatly decreased prolactin synthesis and release but had no effect on growth hormone. Ergocornine, 10 µm, and ergocryptine, 10 µm, almost completely blocked prolactin release and decreased synthesis and release of growth hormone as well.

Daily administration of 0.05 mg ergotamine for 13 days to rats bearing the prolactin- and adrenocorticotropic hormonesecreting pituitary Tumor 7315a dramatically inhibited tumor growth and reversed the adrenal hypertrophy caused by the tumor adrenocorticotropic hormone. Ergotamine, ergocryptine, and ergocornine were all effective in suppressing the growth of pituitary tumors and reversed the splenohepatomegalia caused by growth hormone-secreting tumors. In addition, the ergots decreased the high circulating prolactin levels found in tumor-bearing animals. Ergotamine alone was able to overcome the atrophy of the pituitary glands of tumor-bearing animals and allow gland function to return toward normal. Ergocryptine and ergocornine tended further to suppress gland function. These data demonstrate that hormone synthesis and release by the pituitary gland and pituitary tumors can be inhibited by derivatives of the ergot alkaloids.