Tolbutamideの副腎皮質cortisol及び下垂体prolactin分泌抑制作用

抄録

It has been frequently postulated that insulin-induced hypoglycemia is widely employed clinically to assess the function of the hypothalamo-pituitary axis, being known to stimulate several pituitary trophic hormones such as HGH, ACTH, PRL (Prolactin), etc. Although tolbutamide produces hypoglycemia through the increase of endogenous insulin secretion, in the present study tolbutamide was used instead of insulin, and the effect of tolbutamide on the secretion of PRL from the pituitary gland and also on the secretion of cortisol from the adrenal cortex as well as HGH was studied, using 44 healthy normal subjects (male 35 and female 9, from 15-75 years of age).
(1) PRL : One gram of tolbutamide injected into 5 normal subjects did not increase the serum concentration of PRL up to 120 minutes after the administration of the drug, while the concentration of PRL in the serum was increased clearly by the injection of insulin (0.1U/kg), with maximum PRL levels (approximately 50pg/ml) occurring at 60 minutes after the insulin administration. These results indicated strongly that tolbutamide inhibited the secretion of PRL from the pituitary gland.
(2) Hypothalamo-Pituitary-Adrenal cortex : The same dose of tolbutamide as in the PRL experiment was also injected intravenously, and changes of serum cortisol levels were measured until 180 minutes after the injection of tolbutamide. It was found that levels of serum cortisol were clearly depressed within 30 minutes, and then the cortisol values started to increase up to 120 minutes after the administration of tolbutamide. The stimulatory effect of ACTH on the secretion of cortisol from the adrenal cortex was also strongly abolished by tolbutamide in the early phase as stated above.
The data suggest that tolbutamide might have a direct inhibitory effect on the adrenal cortex as well as on pituitary PRL secretion.