脳におけるホルモン代謝

第3編 ラット脳におけるΔ⁴-3-ketosteroid 5α-oxidoreductaseに及ぼす中枢作用薬の影響(補遺)

抄録

It is considered that endocrine state may be profoundly involved with brain metabolism underlying psychic functions. I have undertaken to study testosterone metabolism in the brain in order to get a basic knowledge about a role of sex hormones, particularly testosterone, playing in psychic function.
In the present investigation, the activity of Δ⁴-3-ketosteroid 5α-oxidoreductase was measured in rat diencephalon, and the effects of central acting drugs were examined on the enzyme activity.
Experimental methods
1. Rats were adrenalectomized and testectomized under Nembutal anaesthesia. One, three, four and six days after the procedure, the activity of Δ⁴-3-ketosteroid 5α-oxidoreductase was determined in rat diencephalon prepared immediately following decapitation. Three days after the operation, another group of rats received intraperitoneal administration of testosterone propionate (1mg/100g. B. W.) and they were killed to determine the enzyme activity in diencephalon.
2. Intact rats had a single i.p. injection of chlorpromazine (4mg/100g. B. W.), diazepam (0.25mg), dipiperon (8mg), methylphenydate (1mg), diphenylhydantoin (5mg), phenobarbital (6mg), caffeine (10mg), methamphetamine (0.6mg), disulfiram (10mg) or normal saline. 4 hours after injection, rats were killed by decapitaion, and both Δ⁴-3-ketosteroid 5α-oxidoreductase activity in diencephalon and plasma testosterone were estimated. Another group of intact rats received repeated i.p. administrations of 1/10 dosis of each drug above mentioned for 14 consecutive days, and the animals were killed 24 hours after the last injection to determine both Δ⁴-3-ketosteroid 5α-oxidoreductase activity in diencephalon and plasma testosterone.
Results
1. The activity of Δ⁴-3-ketosteroid 5α-oxidoreductase was shown to increase gradually until 3 days following adrenalo-testectomy, and then to return to almost normal value. When rats were given testosterone propionate 3 days after adrenalo-testectomy, their enzyme activities in diencephalon fell in to normal range.
2. The activities of Δ⁴-3-ketosteroid 5α-oxidoreductase in diencephalon showed a significant increase (p<0.01) in each group of rats singly administered with carbamazepine, reserpine, diazepam, diphenylhydantoin, phenobarbital or disulfiram, and also a significant increase (p<0.05) in each group given singly methylphenidate, caffeine or methamphetamine. Plasma testosterone showed a decrease in all groups except for diazepam group after a single drug injection.
The enzyme activity in diencephalon showed a significant decrease after repeated drug administrations in disulfiram group (p<0.01) but a significant increase in methamphetamine group (p<0.05). Plasma testosterone showed a tendency for decrease in methamphetamine group but a tendency for increase in disulfiram group.
From the above results, central acting drugs modulating psychic functions were found to act on testosteron-metabolizing enzyme activity. Therefore, it is possible that there exists some relationship between testosterone metabolism in the brain and psychic functions.