Faivre-Bauman A, Loudes C, Barret A, Patte C, Tixier-Vidal A
Groupe de Neuroendocrinologie Cellulaire et Moléculaire, Collège de France, Paris.
Brain Res. 1988 May 16;468(2):261-7. doi: 10.1016/0165-3806(88)90138-1.
The influence of peptidylglycine alpha-amidating monooxygenase (PAM) and of its co-factor, ascorbate, were studied in relation to thyroliberin (TRH) activity during mouse hypothalamus development. In vivo, PAM activity developed slowly at fetal stages, and exhibited a sharp rise around the 5th-8th postnatal day, the adult level being reached around day 15. The same developmental pattern was observed when studied in serum-free cultures initiated from fetal mouse hypothalamus. Using this in vitro model, we investigated the effects of ascorbate, a necessary co-factor of PAM, on TRH. Upon ascorbate supplementation of the culture medium, the TRH accumulation normally occurring in our cultures was further enhanced. The half maximum effect was attained with 20 microM, and the amplitude of the response to ascorbate was maximum around 9-13 days in vitro. Moreover, ascorbate increased to an even larger extent the amounts of TRH released upon chemical depolarization. These results are consistent with a direct role of ascorbate on PAM activity, but other more general effects on the maturation of the neuronal response to physiological stimuli cannot be excluded.
在小鼠下丘脑发育过程中，研究了肽基甘氨酸α-酰胺化单加氧酶（PAM）及其辅因子抗坏血酸对促甲状腺素释放激素（TRH）活性的影响。在体内，PAM活性在胎儿期发育缓慢，在出生后第5 - 8天左右急剧上升，在第15天左右达到成年水平。从胎儿小鼠下丘脑开始的无血清培养研究中也观察到相同的发育模式。利用这个体外模型，我们研究了PAM的必要辅因子抗坏血酸对TRH的影响。在培养基中添加抗坏血酸后，我们培养物中正常发生的TRH积累进一步增强。在20微摩尔时达到最大效应的一半，体外培养9 - 13天左右对抗坏血酸的反应幅度最大。此外，抗坏血酸在化学去极化时释放的TRH量增加的程度甚至更大。这些结果与抗坏血酸对PAM活性的直接作用一致，但不能排除对神经元对生理刺激反应成熟的其他更普遍的影响。
