Robel P, Bourreau E, Corpéchot C, Dang D C, Halberg F, Clarke C, Haug M, Schlegel M L, Synguelakis M, Vourch C
Lab Hormones, Bicêtre, France.
J Steroid Biochem. 1987;27(4-6):649-55. doi: 10.1016/0022-4731(87)90133-6.
The rat brain accumulates pregnenolone (P) as the unconjugated steroid, the sulfate ester (S) and fatty acid esters (L). P + PS do not disappear from rat brain after combined adrenalectomy (adx) and castration (orx). PL does not serve a source of P after adx + orx. P is metabolized by several rat brain regions to progesterone and to PL. Brain microsomes contain the acyl-transferase which converts P to PL using endogenous substrates. Brain P and dehydroepiandrosterone (D) undergo a prominent circadian variation with their acrophases at the beginning of the dark span. The circadian variation of brain D persists after adx + orx. The monkey brain (Macaca fascicularis) also accumulates P and D. Adrenal suppression with dexamethasone for 4 days does not decrease the concentrations of brain P and 3rd ventricle CSFP and D. The concentrations of brain D are decreased to a much smaller extent than plasma D. D inhibits the aggressive behavior of castrated male mice exposed to lactating female intruders. This is not the case for DS or androst-5-ene-3 beta, 17 beta-diol. The D analog 3 beta-methyl-androst-5-en-17-one, which is not estrogenic and cannot be metabolized to testosterone or estradiol, is as active as D in inhibiting the aggressive behavior of castrated mice.
大鼠脑可蓄积孕烯醇酮（P），其形式为未结合甾体、硫酸酯（S）和脂肪酸酯（L）。联合肾上腺切除术（adx）和去势术（orx）后，P + PS不会从大鼠脑中消失。adx + orx后，PL不是P的来源。P在大鼠脑的几个区域被代谢为孕酮和PL。脑微粒体含有酰基转移酶，可利用内源性底物将P转化为PL。脑P和脱氢表雄酮（D）呈现显著的昼夜节律变化，其峰值相位出现在黑暗期开始时。adx + orx后，脑D的昼夜节律变化依然存在。猴脑（食蟹猴）也会蓄积P和D。用 dexamethasone 抑制肾上腺4天不会降低脑P、第三脑室脑脊液压力（CSFP）和D的浓度。脑D浓度的降低程度远小于血浆D。D可抑制暴露于哺乳期雌性入侵者的去势雄性小鼠的攻击行为。对于DS或雄甾-5-烯-3β,17β-二醇则并非如此。D类似物3β-甲基-雄甾-5-烯-17-酮不具有雌激素活性，也不能代谢为睾酮或雌二醇，在抑制去势小鼠的攻击行为方面与D活性相当。
