Laboratory of Endocrine System Development, Research Institute of Human Morphology, FSBSI, Petrovsky National Research Centre of Surgery, 119991 Moscow, Russia.
Department of Histology, Cytology, and Embryology, Federal State Funded Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University, 119435 Moscow, Russia.
Int J Mol Sci. 2022 Apr 28;23(9):4912. doi: 10.3390/ijms23094912.
Epinephrine is the most abundant catecholamine hormone, produced by the nervous system and adrenal glands. Endocrine disruption of epinephrine synthesis, secretion and signaling is less studied than steroid and thyroid hormones. Dichlorodiphenyltrichloroethane (DDT) is recognized as one of the most prominent environmental contaminants with a long half-life. It is a potent endocrine disrupter affecting sex steroid, mineralocorticoid, glucocorticoid and thyroid hormone production. Exposure to low doses of DDT is universal and begins in utero. Therefore, we studied adrenal medulla growth and function in male Wistar rats exposed to low doses of DDT during prenatal and postnatal development until puberty and adulthood, as well as rats exposed to DDT since the first day of postnatal development. All the exposed rats demonstrated lowered epinephrine blood levels, gradually reducing with age. DDT was found to inhibit the synthesis of tyrosine hydroxylase and affect the mitochondrial apparatus of epinephrine-producing cells during puberty and even after maturation. Low-dose exposure to DDT from birth resulted in more pronounced changes in adrenomedullary cells and a more profound decrease (up to 50%) in epinephrine secretion in adult rats. Prenatal onset of exposure demonstrated a mild effect on epinephrine-producing function (30% reduction), but was associated with lower rate of adrenal medulla growth during maturation and 25% smaller adrenal medullar size in adult rats. All subjects exposed to low doses of DDT failed to develop adaptive changes and restore proper epinephrine production. These results indicate a dysmorphogenetic effect of prenatal exposure and disruption of secretory function of adrenal chromaffin cells by postnatal exposure to DDT.
肾上腺素是最丰富的儿茶酚胺激素，由神经系统和肾上腺产生。与类固醇和甲状腺激素相比，肾上腺素的合成、分泌和信号转导的内分泌干扰研究较少。滴滴涕（DDT）被认为是最显著的环境污染物之一，具有很长的半衰期。它是一种强有力的内分泌干扰物，影响性激素、盐皮质激素、糖皮质激素和甲状腺激素的产生。低剂量 DDT 的暴露是普遍存在的，并且从胎儿期开始。因此，我们研究了暴露于低剂量 DDT 的雄性 Wistar 大鼠在产前和产后发育直至青春期和成年期的肾上腺髓质生长和功能，以及从出生后第一天开始暴露于 DDT 的大鼠。所有暴露的大鼠表现出血液中肾上腺素水平降低，随年龄逐渐降低。DDT 被发现抑制酪氨酸羟化酶的合成，并在青春期甚至成熟后影响产生肾上腺素的细胞的线粒体装置。从出生开始接触低剂量 DDT 会导致肾上腺髓质细胞发生更明显的变化，并导致成年大鼠的肾上腺素分泌更显著降低（高达 50%）。产前接触的起始表现出对产生肾上腺素功能的轻度影响（减少 30%），但与成熟期间肾上腺髓质生长率降低以及成年大鼠的肾上腺髓质大小减小 25%相关。所有接触低剂量 DDT 的对象都未能发展出适应性变化并恢复适当的肾上腺素产生。这些结果表明产前接触具有畸形发生作用，并且产后接触 DDT 会破坏肾上腺嗜铬细胞的分泌功能。
