髄液中methionine-enkephalin様物質の測定—正常および下垂体腺腫を中心として

MEASUREMENT OF METHIONINE-ENKEPHALINLIKE SUBSTANCE IN CSF FROM NORMAL SUBJECTS AND PATIENTS WITH PITUITARY ADENOMA

I．はじめに

　近年脳内に鎮痛作用を有する内因性モルヒネ様物質が存在することが知られ^5,11,15），神経伝達物質あるいはホルモンとして注目をあび，多くの知見が報告されている。特にβ—endorphinに関しては特筆すべきものが多く，ACTHと同じ前駆物質から下垂体内で生成されることも明らかになつている^16）。そして臨床的にもCushing病，Nelson病などの下垂体系疾患との関係に関心が集まり，それらにおける動態も明らかになりつつある^23）。これに反してmethioine （met）—enkephalinはその構造がすべてβ—endorphinに含まれていながら^22）血中での測定が困難（血中には存在しないか，すみやかに破壊されるのか不明）なところから，わずかに数グループが髄液中での測定を報告しているにすぎず^{1,14,20,25）}，下垂体系疾患のみならず臨床例での動態についてはほとんど不明で正常値も一般に認められる段階には至つていない。

　われわれは髄液中におけるmet-enkephalin様物質のradioreceptor-assay法を開発し^8），今回下垂体腺腫を中心にした臨床例に応用を試み，興味ある結果を得たので報告する。

Methionine-enkephalin-like substance was meas-ured in CSF by the radioreceptor-assay established by Furui et al. Samples were obtained from pre-operative 20 cases, in which were included 11 cases of pituitary adenoma, 3 cases of craniopharyngioma, 2 cases of pseudtumor cerebri and 4 normal cases, by lumbar puncture. Also postoperative measure-ment of this substance and pre- and postoperative measurement of ACTH in plasma were performed in 5 cases of Cushing's disease. Five ml of CSF was chromatograpied on two succesive columns, lyophilized and assayed for opiate receptor affinity against ³H-dihydromorphine. Measured values were expressed as methionine-enkephalin equiva-lents using the displacement curve run in parallel.

Methionine-enkephalin-like substance level ranged from<0.5 to 20.0 pmoles/ml in all cases and mean value was 2.6 pmoles/ml (±1.0 S.E.) in normal subjects. In Cushing's disease the level was not elevated preoperatively (2.1±0.3) and did not sig-nificantly decrease postoperatively (1.6±0.4 pmoles/ ml) in contrast to the decrease of ACTH in plasma. It is suggested that methionine-enkephalin-like substance in CSF is not derived from ACTH producing cells of pituitary gland. One case of craniopharyngioma showed very high value. This case revealed diabetes insipidus at sampling. The possibility of participation of methionine-enkephalin in secretion of antidiuretic hormone was discussed.