Carvalho Janaine C, Lisboa Patricia C, de Oliveira Elaine, Peixoto-Silva Nayara, Nobre Jessica L, Fraga Mabel C, Manhães Alex C, Moura Egberto G
Laboratory of Endocrine Physiology, Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ 20551-031, Brazil.
Laboratory of Endocrine Physiology, Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ 20551-031, Brazil.
Neuropeptides. 2016 Oct;59:71-81. doi: 10.1016/j.npep.2016.05.003. Epub 2016 May 24.
Previously, we demonstrated that maternal prolactin inhibition at the end of lactation, using bromocriptine (BRO), leads to an increase in leptin transfer via milk and induces the adult progeny to present hypothyroidism, leptin resistance and metabolic syndrome (obesity, hyperglycemia, hypertriglyceridemia, lower HDL). To test if these alterations are due to direct BRO action on the pups, in the present study we evaluated the long-term effects of direct injection of BRO (0.1μg/once daily) in male Wistar rats from postnatal (PN) day 1 to 10 (early treatment) or from PN11 to 20 (late treatment) on: food intake, body mass, cardiovascular parameters, hormone profile, hypothalamic leptin signaling, glucose homeostasis and thyroid hormone-dependent proteins. The respective controls were injected with methanol-saline. Offspring were killed at adulthood (PN180). Adult PN1-10 BRO-treated animals had lower food intake, hypoprolactinemia, lower leptin action (lower OBR-b, STAT-3 and SOCS-3 mRNA levels in the arcuate nucleus), lower TRH-TSH-thyroid axis as well as lower thyroid hormone markers. On the other hand, adult animals that were BRO-treated during the PN11-20 period showed hyperphagia, higher blood pressure, higher prolactinemia and OBR-b, higher TRH and plasma T3, hypercorticosteronemia as well as higher Dio2 and UCP1 mRNA expression in the brown adipose tissue. Glucose homeostasis was not changed treatment in either period. Our data show that early and late dopamine overexposure during lactation induces diverse metabolic disturbances later in life, increasing the risk of thyroid dysfunction and, consequently, changes in prolactinemia.
此前,我们证明在哺乳期结束时使用溴隐亭(BRO)抑制母体催乳素会导致瘦素通过乳汁的转运增加,并诱导成年子代出现甲状腺功能减退、瘦素抵抗和代谢综合征(肥胖、高血糖、高甘油三酯血症、低高密度脂蛋白)。为了测试这些改变是否是由于BRO对幼崽的直接作用,在本研究中,我们评估了从出生后(PN)第1天至10天(早期治疗)或从PN11至20天(晚期治疗)给雄性Wistar大鼠直接注射BRO(0.1μg/每日一次)对以下方面的长期影响:食物摄入量、体重、心血管参数、激素谱、下丘脑瘦素信号传导、葡萄糖稳态和甲状腺激素依赖性蛋白。相应的对照组注射甲醇盐水。子代在成年期(PN180)处死。成年期PN1 - 10接受BRO治疗的动物食物摄入量较低、催乳素血症较低、瘦素作用较低(弓状核中OBR - b、STAT - 3和SOCS - 3 mRNA水平较低)、TRH - TSH - 甲状腺轴较低以及甲状腺激素标志物较低。另一方面,在PN11 - 20期间接受BRO治疗的成年动物表现出食欲亢进、血压升高、催乳素血症和OBR - b升高、TRH和血浆T3升高、高皮质酮血症以及棕色脂肪组织中Dio2和UCP1 mRNA表达升高。在两个时期,葡萄糖稳态均未因治疗而改变。我们的数据表明,哺乳期早期和晚期多巴胺过度暴露会在生命后期引发多种代谢紊乱,增加甲状腺功能障碍的风险,并因此导致催乳素血症的变化。