Villa M, Ménard D, Semenza G, Mantei N
Department of Biochemistry, Swiss Federal Institute of Technology, ETH Zentrum, Zürich.
FEBS Lett. 1992 Apr 20;301(2):202-6. doi: 10.1016/0014-5793(92)81248-k.
Very sensitive procedures were developed for the parallel determination of intestinal lactase (LPH) activity and the cognate mRNA. Between 14 and 20 weeks of gestation, lactase activity is low and varies only slightly; at 37 weeks, a relatively high level of activity is observed. The amounts of LPH mRNA correlates with the enzymatic activity (r = 0.64). Culture of fetal jejunal explants for 5 days induces by itself a 2-fold increase in LPH mRNA, without any significant change in lactase enzymatic activity. This increase may reflect the loss of a negative transcriptional regulation operative in vivo, and suggests an additional post-transcriptional regulatory component. The addition of hydrocortisone (50 ng/ml) during culture induces a doubling of lactase activity without variation in LHP mRNA, indicating a post-transcriptional modulation by hydrocortisone. The intestinal lysosomal acid beta-galactosidase activity was shown to be unaffected by hydrocortisone treatment. This observation clearly illustrates that the two intestinal beta-galactosidases are regulated differently. Our results suggests a complex developmental regulation of human intestinal lactase and that the perinatal increase in lactase activity could be modulated at a post-transcriptional level by hydrocortisone.
已经开发出非常灵敏的方法用于同时测定肠道乳糖酶(LPH)活性和相关mRNA。在妊娠14至20周期间,乳糖酶活性较低且变化很小;在37周时,观察到相对较高的活性水平。LPH mRNA的量与酶活性相关(r = 0.64)。将胎儿空肠外植体培养5天本身会使LPH mRNA增加2倍,而乳糖酶活性没有任何显著变化。这种增加可能反映了体内存在的负转录调节的丧失,并提示存在额外的转录后调节成分。在培养过程中添加氢化可的松(50 ng/ml)会使乳糖酶活性加倍,而LHP mRNA没有变化,表明氢化可的松进行了转录后调节。肠道溶酶体酸性β-半乳糖苷酶活性显示不受氢化可的松处理的影响。这一观察结果清楚地表明,两种肠道β-半乳糖苷酶的调节方式不同。我们的结果提示人类肠道乳糖酶存在复杂的发育调节,并且围产期乳糖酶活性的增加可能在转录后水平受到氢化可的松的调节。