Lisboa P C, de Oliveira E, Manhães A C, Santos-Silva A P, Pinheiro C R, Younes-Rapozo V, Faustino L C, Ortiga-Carvalho T M, Moura E G
Laboratory of Endocrine PhysiologyLaboratory of NeurophysiologyBiology Institute, State University of Rio de Janeiro, Rio de Janeiro 20551-030, BrazilCarlos Chagas Filho Biophysic InstituteFederal University of Rio de Janeiro, Rio de Janeiro 21949-900, Brazil.
Laboratory of Endocrine PhysiologyLaboratory of NeurophysiologyBiology Institute, State University of Rio de Janeiro, Rio de Janeiro 20551-030, BrazilCarlos Chagas Filho Biophysic InstituteFederal University of Rio de Janeiro, Rio de Janeiro 21949-900, Brazil
J Endocrinol. 2015 Mar;224(3):315-25. doi: 10.1530/JOE-14-0473. Epub 2015 Feb 4.
Postnatal nicotine exposure leads to obesity and hypothyroidism in adulthood. We studied the effects of maternal nicotine exposure during lactation on thyroid hormone (TH) metabolism and function in adult offspring. Lactating rats received implants of osmotic minipumps releasing nicotine (NIC, 6 mg/kg per day s.c.) or saline (control) from postnatal days 2 to 16. Offspring were killed at 180 days. We measured types 1 and 2 deiodinase activity and mRNA, mitochondrial α-glycerol-3-phosphate dehydrogenase (mGPD) activity, TH receptor (TR), uncoupling protein 1 (UCP1), hypothalamic TRH, pituitary TSH, and in vitro TRH-stimulated TSH secretion. Expression of deiodinase mRNAs followed the same profile as that of the enzymatic activity. NIC exposure caused lower 5'-D1 and mGPD activities; lower TRβ1 content in liver as well as lower 5'-D1 activity in muscle; and higher 5'-D2 activity in brown adipose tissue (BAT), heart, and testis, which are in accordance with hypothyroidism. Although deiodinase activities were not changed in the hypothalamus, pituitary, and thyroid of NIC offspring, UCP1 expression was lower in BAT. Levels of both TRH and TSH were lower in offspring exposed to NIC, which presented higher basal in vitro TSH secretion, which was not increased in response to TRH. Thus, the hypothyroidism in NIC offspring at adulthood was caused, in part, by in vivo TRH-TSH suppression and lower sensitivity to TRH. Despite the hypothyroid status of peripheral tissues, these animals seem to develop an adaptive mechanism to preserve thyroxine to triiodothyronine conversion in central tissues.
出生后尼古丁暴露会导致成年期肥胖和甲状腺功能减退。我们研究了哺乳期母体尼古丁暴露对成年后代甲状腺激素（TH）代谢和功能的影响。从出生后第2天到第16天，给哺乳期大鼠植入渗透微型泵，释放尼古丁（NIC，每天皮下注射6毫克/千克）或生理盐水（对照）。在180天时处死后代。我们测量了1型和2型脱碘酶活性及mRNA、线粒体α-甘油-3-磷酸脱氢酶（mGPD）活性、TH受体（TR）、解偶联蛋白1（UCP1）、下丘脑TRH、垂体TSH以及体外TRH刺激的TSH分泌。脱碘酶mRNA的表达与酶活性的变化趋势相同。NIC暴露导致5'-D1和mGPD活性降低；肝脏中TRβ1含量降低以及肌肉中5'-D1活性降低；棕色脂肪组织（BAT）、心脏和睾丸中5'-D2活性升高，这与甲状腺功能减退相符。尽管NIC后代的下丘脑、垂体和甲状腺中的脱碘酶活性没有变化，但BAT中UCP1的表达较低。暴露于NIC的后代中TRH和TSH水平均较低，其体外基础TSH分泌较高，对TRH无反应性增加。因此，NIC后代成年期的甲状腺功能减退部分是由体内TRH-TSH抑制和对TRH敏感性降低引起的。尽管外周组织处于甲状腺功能减退状态，但这些动物似乎形成了一种适应性机制来维持中枢组织中甲状腺素向三碘甲状腺原氨酸转化。
