クッシング病下垂体腺腫のin vitroにおけるACTH分泌動態

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Selective adenomectomy of patients with Cushing's disease results in marked clinical improvement and recovery of normal pituitary-adrenal function, including diurnal rhythm. These findings tend to exclude a hypothalamic origin of Cushing's disease; nevertheless its etiology is controversial. The present in in vitro study was designed to investigate the autonomy of ACTH secretion from the adenoma under the absence of a hypothalamic regulatory mechanism. Fragments of the pituitary adenomas from seven patients with Cushing's disease were placed in primary culture immediately after surgery. Hormonal release was studied from two weeks to three months depending upon the survival culture. Adenoma tissue was proved to release continuously a high concentration of ACTH into the medium for a month. ACTH was still detectable in one case even after three months. Contrarily, ACTH secretion from residual anterior pituitary tissue in Cushing's disease and normal pituitary decreased rapidly and became undetectable within a few weeks in vitro. In addition to the explant culture study, the effect of lysine-vasopressin (LVP) on ACTH secretion from perfused adenoma tissue was examined, since clinical data in the ACTH response to LVP before and after surgery argues that the conspicuous preoperative response is caused by adenoma. ACTH secretion was induced with little or no latency after LVP infusion in seven out of eight cases. However, a dose-response relationship was not obtained between the LVP concentrations and the magnitude of ACTH responses. The in-fusion of dexamethasone, on the other hand, inhibited ACTH secretion in only one of four cases. These data suggest that the autonomy of ACTH secretion may exist in the adenoma of Cushing's disease and that LVP acts directly on adenoma tissue such as proposed by clinical data. From our clinical results and experimental studies in vitro, it can be concluded that the primary lesion in Cushing's disease seems to be in the pituitary gland rather than in the hypothalamus.
日本内分泌学会の論文

クッシング病下垂体腺腫のin vitroにおけるACTH分泌動態

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