Effects of maternal nicotine exposure on thyroid hormone metabolism and function in adult rat progeny

Abstract

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 a-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 0 -D1 and mGPD activities; lower TRb1 content in liver as well as lower 5 0 -D1 activity in muscle; and higher 5 0 -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.

Maternal High-Fat Diet Disturbs the DNA Methylation Profile in the Brown Adipose Tissue of Offspring Mice

“…Obesity is a multi-factorial disease. In addition to genetic factors, environmental changes also contribute to the incidence of obesity, especially during critical developmental periods, such as gestation and lactation (6). Epidemiological data indicates that a maternal high-fat diet is one of the key risk factors for childhood obesity (7,8).…”

Effect of Preeclampsia on Ultrastructure of Thyroid Gland, Hepatic Type 1 Iodothyronine Deiodinase, and Thyroid Hormone Levels in Rats

“…About 80% of circulating T 3 is derived from the metabolic transformation: the extrathyroidal peripheral conversion of T 4 to T 3 [ 23 ]. The peripheral conversion is mainly catalyzed by type 1 iodothyronine deiodinase (Dio1) [ 24 ], which is predominantly expressed in the liver [ 25 ].…”