ACTHの臨床的研究:第2編合成Lysine VasopressinによるACTH分泌機構について
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The mechanism of pituitary ACTH secration under various conditions and various endocrine disorders was studied by a synthetic lysine vasopressin (L-8-V) which was re-ported to possess a corticotrophin releasing factor-like activity. Variations in the level of the plasma cortisol were used as an index of ACTH release. Blood samples were drawn before, 15 and 30 minutes after the injection of L-8-V and the concentration of plasma cortisol was determined by a fluorescence method.<BR>Concerning the response of plasma cortisol to various doses of L-8-V, it was revealed that the intravenous injection of 4 units of L-8-V produced a great response, as compared with the intravenous injection of 3 and 2 units respectively and the intramuscular injection of 10 units. Therefores, plasma cortisol response to the intravenous injection of 4 units of L-8-V was standardised as a pituitary function test.<BR>The results of the clincal investigations are summaresed as follows : <BR>L-8-V dose not seem to possess an ACTH-like activity, since no plasme cortisol response was produced in the subjets treated with L-8-V during the infusion of 4 mg of dexamethasone. No response to L-8-V was observed in patients with idiopathic hypopituitarism, patient with acromegaly and patients with craniopharyngioma, though a plasma cortisol response to ACTH was still maintained in those patients.. Although it is un-known whether the L-8-V-induced ACTH release is based on its CRF-like activity, or mediated by the stimulation of CRF secretion, L-8-V is thought to be a kind of stress from its side effects.<BR>A study was made on the effect of an administration of L-8-V as a corticotropin releaser during various times of the circadian rhythm of the plasma cortisol. The material was administered at 10 : 00 a.m. 4 : 00 p.m. and 10 : 00 p.m.<BR>The response to 4 units of L-8-V at 10 : 00 a.m. in 11 subjects resulted in a rise of the plasma cortisol from a mean of 8.8±2.6μg/dl to levels of 14.1±1.9μg/dl at 15 minutes, 14.6±2.5μg/di at 30 minutes;at 4 : 00 p.m. in 5 subjects, from a mean of 6.2±2.8μg/dl to levels of 12.1±2.9 μg/dl at 15 minutes, 14.2±4.7 μg/dl at 30 minutes; at 10 : 00 p.m. in 9 subjects, from a mean of 4.9±1.5μg/sl to levels of 11.6±3.7μg/dl at 15 minutes, 11.9±4.6 μg/dl at 30 minutes.<BR>The response to 250 μg of synthetic ACTH at 10 : 00 a.m. in 7 subjects resulted in a rise of the plasma cortisol from a mean of 10.7±4.1 μg/dl to level of 18.4±4.1 μg/dl at 90 minutes ; at 9 : 00 p.m. in 8 subjects from a mean of 4.4±2.1μg/dl to level of 17.8±3.7μg/dl at 90 minutes.<BR>These data suggest that responsiveness to both L-8-V and ACTH was not significantly different at night from day time. It was assumed that too much ACTH exceedeing the asrenal capacity acted on the adrenal cortex during a short time in both cases.<BR>A study was made on the effect of L-8-V in patients with pituitary adrenal function suppressed by a small dose of dexamethasone. In one group of patients who received 0.5 mg of dexamethasone at midnight, there was a significant rise of plasma cortisol level by the stimulation with L-8-V given at 8 : 00 a.m. However, in the other group of pattients who received 0.5 mg of dexamethasone at 8 : 00 a.m. there was no response to L-8-V given at 4 : 00 p.m. By the pretreatment with 1.5 mg at midnight, the response to L-8-V at 8 : 00 a.m. was suppressed. The result indicates that the responsiveness to L-8-V was greater in the morning than in the evening under the condition of the incomplete pituitary adrenal function caused by the administration of 0.5 mg of dexamethasone. This suggests that a pituitary ACTH secretion in response to stress is more active in the morning than in the evening.
- 日本内分泌学会の論文