Quadri SK.
“Effects Of Central Acting Drugs And Ergot Derivatives On Prolactin And Growth Hormone Secretion, On Growth Of Pituitary And Mammary Tumors And On Reproduction In Old Rats”.
Assertation Abst. Intern. B. 1974;34(6181-B):319.
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Abstract
1. A single-intraperitoneal injection of the ergot derivetives, ergocryptine, or LSD (lysergic acid diethylamide), significantly decreased serum prolactin levels in female rats and blocked the rise in prolactin that normally occurs in control rats on the afternoon of proestrus. A single dose of ergocryptine remained effective for at least 24 hours after it was administered. Ergocryptine was not able to block the increase in prolactin secretion induced by perphenazine, which exerts its effects on the hypothalamus. The primary action of ergocryptine appears to be directly on the pituitary gland. 2. A single intraperitoneal injection of 1, 8 or 12 mg pyro - lol per 100 g body weight caused a significant reduction in serum prolactin levels in female rats. Pyrogallol inhibits degradation of catecholamines, and an increase in catechol - amines results in reduced prolactin secretion. 3. A single intraperitoneal injection of sodium pentobar - bital produced an initial rise followed by a fall in plasma growth hormone (GH). Ether anesthesia consistently reduced plasma GH levels. Contrary to their inhibitory effects on GH secretion in rats, stresses of various kinds stimulate GH re - lease in man and other species. 4. Daily injections of epinephrine, l-dopa or iproniazid for 25 days into 20 to-23 month old constant estrous Sprague - Dawley rats initiated regular estrous cycles in most rats. On termination of treatment, a few rats continued to cycle but the majority returned to a state of constant estrous or went into a prolonged diestrus. N was concluded that all three drugs restored regular cycling by correcting a catecholamine de - ficiency in the hypothalamus, thereby increasing LH and FSH and decreasing release of prolactin. 5. Inbred female Wistar-Furth rats were transplanted with the mammosomatotropic pituitary tumor, MtT. W15. About 6 weeks after transplantation, weekly measurements were made of plasma GH, serum prolactin, tumor size and body weights. A highly significant and positive correlation as found between tumor size and prolactin and GH levels, and between tumor size and body weight. Age of tumor was not always related to the secretory activity or size of the tumor. 6. Daily treatment of rats carrying pituitary tumor trans - plants with ergocornine produced regression of tumor growth, degeneration of tumor tissue and suppression of prolactin but not GH secretion. Ergocornine is believed to inhibit prolactin secretion by a direct action on the pituitary tumor. Ergono - vine also inhibited tumor growth but ergocryptine and a thali - domide-related compound, CG 603, both of which inhibit pro - lactin release by the normal in situ pituitary, had no effect on the size or secretory activity of the tumor. 7. Ergocornine and ergocryptine produced marlsed regres - sion of spontaneous mammary tumors in old female rats. It was concluded that the ergot derivatives inhibited mammary tumor growth by depressing prolactin secretion 8. The ergot derivatives, ergocornine and LSD, also in - hibited growth of carcinogen-induced mammary tumors. The anticancer activity of ergocornine was enhanced by simul - taneous treatment with ovariectomy or large doses of estra - diol benzoate which further decreased prolactin secretion and/or interfered with the peripheral action of prolactin on mammary tumors, respectively. 9. Drostanolone propionate, a modified testosterone compund, was found to be a potent inhibitor of growth of carcinogen-induced mammary tumors in rats. However, its inhibitory effects on turmor growth were completely overcome by simutaneous injections of prolectin. It is suggested that high doses of androgens, like high doses of estrogens, inhibit mammary tumor growth by interfering with the peripheral action of prolactin on tumor parenchyma. 10. Convincing evidence was obtained that mammary tumor growth can be altered by altering catecholamine activicty in the hypothalamyus. Thus treatment with 1-dopa or pargyline, which increase catecholamines in the hypothalamus and thereby reduce prolactin release, produced marked regression of esablished tumors and complete suppression of new tumor development. By contrast, methyldopa and haloperidol produced profound stimulation of mammary tumor growth both these drugs produce several fold increases in prolactin secretion by decreasing hypothalamic catecholamine activity.
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