Effects of 6-methoxy-1,2,3,4-tetrahydro-beta-carboline and yohimbine on hypothalamic monoamine status and pituitary hormone release in the rat.
Shortly after administration of 6-methoxy-1,2,3,4-tetrahydro-beta-carboline (6-MeOTHBC) and yohimbine to normal or hypothyroid rats [the latter exhibiting chronically elevated levels of serotonin (5-HT) neuronal activity in the hypothalamus] there was a highly significant increase in hypothalamic noradrenaline (NA) activity and in ACTH release concomittant with a reduction in hypothalamic 5-HT activity (P less than 0.01) and in growth hormone (GH) (P less than 0.01) and in thyroid stimulating hormone (TSH) (P less than 0.01) release from the pituitary. Both compounds caused an increase in hypothalamic dopamine (DA) metabolism and in pituitary prolactin (PRL) release in normal rats (P less than 0.01) but only yohimbine exerted this action in hypothyroid rats. Lower doses of 6-MeOTHBC exerted a relatively specific effect in hypothyroid rats, reducing (P less than 0.01) 5-HT neuronal activity in parallel with pituitary TSH secretion (P less than 0.05). While gross effects of 6-MeOTHBC and yohimbine were similar with respect to their effects on NA and 5-HT status in the hypothalamus, there were quantitative differences. 6-MeOTHBC always caused a greater decrease in 5-HT turnover and a lesser increase in NA turnover than did yohimbine. On the basis of these studies we suggest that the effect of tetrahydro-beta-carboline-related alkaloids on pituitary hormone release may be due to their influence on hypothalamic monoamine status and the subsequent alteration of the hypothalamic-pituitary control system.
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D002243:Carbolines / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood; D004298:Dopamine / Q000378:metabolism; D013006:Growth Hormone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007031:Hypothalamus / Q000502:physiology; D007037:Hypothyroidism / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D011388:Prolactin / Q000097:blood; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology*
D002243:Carbolines; D007211:Indoles; C002272:6-methoxytryptoline; D015016:Yohimbine; D012701:Serotonin; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D013006:Growth Hormone; D008995:Monoamine Oxidase; D004298:Dopamine; D003345:Corticosterone; D009638:Norepinephrine