Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
Life Sci. 2010 Jul 31;87(5-6):187-95. doi: 10.1016/j.lfs.2010.06.012. Epub 2010 Jun 28.
Postnatal nicotine exposure causes precocious primary hypothyroidism and programs for overweight, hyperleptinemia and secondary hypothyroidism in adulthood. As leptin and thyroid hormones share the ability to increase energy expenditure, we studied the effects of maternal nicotine exposure during lactation on the leptin signaling in the hypothalamus-pituitary-thyroid axis of suckling and adult offspring.
Two days after delivery, osmotic minipumps were implanted in lactating rats, and nicotine (NIC, 6 mg/kg/day s.c.) or saline (C) was administered for 14days. Offspring were killed at 15 and 180 days-old. Proteins belonging to leptin signaling were analyzed by Western blot. Significant differences had p<0.05.
In the hypothalamus, NIC offspring showed higher OB-R and pSTAT-3 content (+58%,+1.34x) at 15 days, and lower OB-R, JAK-2 and pSTAT-3 (-61%, -42%, -56%) at 180 days. In the pituitary gland, NIC offspring showed lower JAK-2 content (-52%) at 15 days, but no differences in adulthood. In the thyroid gland, the NIC group presented lower OB-R, JAK-2 and STAT-3 (-44%, -50%, -47%) and higher pSTAT-3 expression (+80%) at 15 days. At 180 days-old, NIC offspring presented higher thyroid OB-R (+1.54x) and lower pSTAT-3 content (-34%).
Neonatal primary hypothyroidism induced by maternal nicotine exposure during lactation may be partially explained by decreased leptin signaling in the thyroid, though the early stimulation of the central leptin pathway did not prevent the thyroid dysfunction. Long-term effects of postnatal nicotine exposure on leptin signaling in the hypothalamus and thyroid appear to involve central and peripheral leptin resistance in adulthood.
产后尼古丁暴露可导致婴儿甲状腺功能减退症，并导致成年后超重、高瘦素血症和继发性甲状腺功能减退症。由于瘦素和甲状腺激素都具有增加能量消耗的能力，我们研究了哺乳期母体尼古丁暴露对哺乳期和成年后代下丘脑-垂体-甲状腺轴中瘦素信号的影响。
分娩后 2 天，在哺乳期大鼠中植入渗透型微量渗透泵，皮下给予尼古丁（NIC，6mg/kg/天）或生理盐水（C）14 天。在 15 天和 180 天处死后代。用 Western blot 分析瘦素信号相关蛋白。有统计学差异的 p<0.05。
在 15 天时，NIC 后代下丘脑 OB-R 和 pSTAT-3 含量更高（+58%，+1.34 倍），180 天时 OB-R、JAK-2 和 pSTAT-3 含量更低（-61%，-42%，-56%）。在垂体中，NIC 后代在 15 天时 JAK-2 含量更低（-52%），但成年后没有差异。在甲状腺中，NIC 组 15 天时 OB-R、JAK-2 和 STAT-3 更低（-44%，-50%，-47%），pSTAT-3 表达更高（+80%）。在 180 天，NIC 后代甲状腺 OB-R 更高（+1.54 倍），pSTAT-3 含量更低（-34%）。
哺乳期母体尼古丁暴露引起的新生儿原发性甲状腺功能减退症可能部分归因于甲状腺中瘦素信号的降低，尽管早期刺激中枢瘦素途径并不能防止甲状腺功能障碍。产后尼古丁暴露对下丘脑和甲状腺瘦素信号的长期影响似乎涉及成年后中枢和外周瘦素抵抗。
