Toste F P, Alves S B, Dutra S C P, Bonomo I T, Lisboa P C, Moura E G, Passos M C F
Department of Physiological Sciences, State University of Rio de Janeiro, RJ, Brazil.
Horm Metab Res. 2006 Dec;38(12):827-31. doi: 10.1055/s-2006-956502.
Hormones and malnutrition can imprint several changes in the beginning of life that programs homeostatic changes in the adulthood. We analyzed the thyroid function in 21, 30, 60 and 150 days old animals that were injected with leptin on the first 10 days of life, to determine whether this corresponds to a critical period for the establishment of the hormonal imprinting in the programming of the thyroid function. Pups were divided, within 24 hours of birth, into two groups: Lep group, which was injected once daily with 8 microg/100 g B.W. of recombinant mouse leptin for the first 10 days of lactation, and C-control group that received the same volume of saline. Lep group had higher leptin concentration at days 30 (+6 x , p<0.001) and 150 (+108%, p<0.05) than the controls. These animals had lower serum TT4 (-13%; p<0.05) and TT3 (-17.3%; p<0.002) at 30 days and higher serum TT4 and FT4 concentrations at 150 days (+17.5% and +10%, p<0.05 %, respectively, p<0.05) with lower serum TSH concentrations at 60 (-38.5%, p<0.05) and 150 days (-46%, p<0.05). These animals had also lower hepatic mitochondrial alpha-glycerol-3-phosphate dehydrogenase (mGPDH) activity at 21 (-22.5%; p<0.05), 30 (-50.4%; p<0.05) and 150 days (-40%; p<0.05) than the controls. These data show that the leptin injection in the beginning of lactation cause a hypothyroidism on the offspring as soon as 30 days of age and this alteration may be the imprinted factor for the programming of a higher thyroid function at the adulthood.
激素和营养不良会在生命早期引发多种变化,这些变化会为成年期的稳态变化设定程序。我们分析了在出生后前10天注射瘦素的21日龄、30日龄、60日龄和150日龄动物的甲状腺功能,以确定这是否对应于甲状腺功能编程中激素印记建立的关键时期。幼崽在出生后24小时内被分为两组:Lep组,在哺乳期的前10天每天注射一次8微克/100克体重的重组小鼠瘦素;C对照组,接受相同体积的生理盐水。Lep组在30日龄(+6倍,p<0.001)和150日龄(+108%,p<0.05)时的瘦素浓度高于对照组。这些动物在30天时血清总甲状腺素(TT4)(-13%;p<0.05)和总三碘甲状腺原氨酸(TT3)(-17.3%;p<0.002)较低,而在150天时血清TT4和游离甲状腺素(FT4)浓度较高(分别为+17.5%和+10%,p<0.05),在60日龄(-38.5%,p<0.05)和150日龄(-46%,p<0.05)时血清促甲状腺激素(TSH)浓度较低。这些动物在21日龄(-22.5%;p<0.05)、30日龄(-50.4%;p<0.05)和150日龄(-40%;p<0.05)时肝脏线粒体α-甘油-3-磷酸脱氢酶(mGPDH)活性也低于对照组。这些数据表明,哺乳期开始时注射瘦素会使后代在30日龄时就出现甲状腺功能减退,这种改变可能是成年期甲状腺功能较高编程的印记因素。