Laboratorio de Toxicología Experimental, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 570, 2000 Rosario, Argentina.
Toxicology. 2010 Apr 30;271(1-2):13-20. doi: 10.1016/j.tox.2010.01.016. Epub 2010 Feb 1.
The effects of 2,4-dichlorophenoxyacetic acid (2,4-D) on brain monoamines and the serum level of hormones involved in milk synthesis and on the milk ejection reflex in rats were evaluated. Dams were treated with 2.5, 5, 15, 25, 50 or 70mg 2,4-D/kg bw according to two experimental designs: (a) through food from post partum day 1 (PPD 1) to PPD 16 and the respective control groups or (b) an unique i.p. injection on PPD 11. To measure milk ejection, the litter was separated from the mother at the 11th day of lactation during 8h, returned to their mothers and allowed to suckle for a period of 15min. The procedure was repeated on 3 consecutive days until the end of treatment. The change in litter weight during the suckling period was taken as a measure of the amount of milk ejected during this period. The dams' serum prolactin (PRL), oxytocin (OT) and growth hormone levels were determined by radioimmunoassay. Both treatment regimens produced a dose-dependent decrease in the amount of milk ejected and circulating PRL and OT secreted in response to the suckling stimulus. Administration of OT before returning the pups restored the milk ejection, indicating no impairment in the capacity of the mammary gland to produce and secrete milk. In addition, dopamine levels were increased by the 2,4-D treatments in arcuate nucleus (ArN) and anterior lobe of pituitary gland (AL), while serotonin level was drastically decreased in ArN. 2,4-D treatment increased both calcium-dependent and calcium-independent nitric oxide synthase (NOS) activities in ArN. These results suggest that 2,4-D inhibits the suckling-induced hormone release, milk transfer to the litter at the central level, through a stimulation of hypothalamic NOS and dopamine and by an inhibition of hypothalamic serotonin transmission.
评估了 2,4-二氯苯氧乙酸（2,4-D）对大鼠脑单胺类物质和参与乳汁合成的激素的血清水平以及乳汁排出反射的影响。根据两种实验设计，用 2.5、5、15、25、50 或 70mg 2,4-D/kg bw 对母鼠进行处理：（a）从产后第 1 天（PPD 1）到 PPD 16 通过食物喂养，并与相应的对照组进行比较；（b）在 PPD 11 时进行单次腹腔注射。为了测量乳汁排出量，在哺乳期第 11 天，将幼崽从母鼠身上分离 8 小时，然后将其放回母鼠身边，并允许它们吮吸 15 分钟。在连续 3 天内重复该过程，直到治疗结束。在此期间，通过幼崽体重的变化来衡量这段时间内排出的乳汁量。通过放射免疫分析法测定母鼠血清中催乳素（PRL）、催产素（OT）和生长激素的水平。两种处理方案均导致乳汁排出量以及对吮吸刺激分泌的循环 PRL 和 OT 呈剂量依赖性减少。在将幼崽送回之前给予 OT 可恢复乳汁排出，表明乳腺产生和分泌乳汁的能力没有受损。此外，2,4-D 处理增加了弓状核（ArN）和垂体前叶（AL）中的多巴胺水平，而 ArN 中的 5-羟色胺水平则急剧下降。2,4-D 处理增加了 ArN 中钙依赖性和钙非依赖性一氧化氮合酶（NOS）的活性。这些结果表明，2,4-D 通过刺激下丘脑 NOS 和多巴胺的释放以及抑制下丘脑 5-羟色胺的传递，从而抑制了吮吸引起的激素释放、乳汁向幼崽的转移，从而抑制了乳汁的分泌。
