Neonatal Low-Protein Diet Changes Deiodinase Activities and Pituitary TSH Response to TRH in Adult Rats

Mounting evidence led us to hypothesize that i) function of the thyroid hormone (TH) axis can be programed by late gestation undernutrition (LG-UN) and ii) early-postnatal-life overnutrition (EL-ON) exacerbates the fetal impacts on TH axis function. In a 2!2 factorial experiment, 21 twin-bearing sheep were fed one of two diets during late gestation: NORM (fulfilling energy and protein requirements) or LOW (50% of NORM). From day 3 to 6 months after birth (around puberty), the twin lambs were assigned to each their diet: conventional (CONV) or high-carbohydrate, high-fat, where after half the lambs were killed. Remaining sheep (exclusively females) were fed the same moderate diet until 2 years of age (young adults). At 6 months and 2 years of age, fasting challenges were conducted and target tissues were collected at autopsy. LG-UN caused adult hyperthyroidism associated with increased thyroid expression of genes regulating TH synthesis and deiodination. In one or more of the target tissues, liver, cardiac muscle, and longissimus dorsi muscle, gene expressions were increased by LG-UN for TH receptors (THRA and THRB) and deiodinases but were decreased in visceral and subcutaneous adipose tissues. EL-ON increased TH levels in adolescent lambs, but this was reversed after diet correction and not evident in adulthood. We conclude that LG-UN programed TH axis function at the secretory level and differentially in target tissues, which was increasingly manifested with age. Differential TH signaling in adipose vs other tissues may be part of a mechanism whereby fetal malnutrition can predispose for obesity and other metabolic disorders.

Section: Effects Of Lg-un In Adult Sheepsupporting

confidence: 62%

Prenatal undernutrition and postnatal overnutrition alter thyroid hormone axis function in sheep

Johnsen

Kongsted

Nielsen

2013

“…Thus, these explanations may help to understand the mechanism by which the maternal hypoprolactinemia during lactation permanently change the thyroid function. Perhaps this change can turn undernourished children more susceptible to thyroid disorders in adult life , Dutra et al 2003, Lisboa et al 2008, although it deserves epidemiological and prospective studies.…”

Section: Discussionmentioning

confidence: 99%

“…We have suggested a relationship between neonatal nutritional status and thyroid function in adult life, because we have demonstrated that maternal protein malnutrition during lactation programs for a hyperthyroidism at adulthood in rodents , Dutra et al 2003, Lisboa et al 2008. Recently, it was reported that women with low birth weight had a higher prevalence of hypothyroidism in adulthood (Kajantie et al 2006).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Prolactin inhibition at the end of lactation programs for a central hypothyroidism in adult rat

Bonomo

Lisboa²,

Passos³

et al. 2008

Malnutrition during lactation is associated with hypoprolactinemia and failure in milk production. Adult rats whose mothers were malnourished presented higher body weight and serum triiodothyronine (T 3 ). Maternal hypoprolactinemia at the end of lactation caused higher body weight in adult life, suggesting an association between maternal prolactin (PRL) level and programming of the offspring's adult body weight. Here, we studied the consequences of the maternal PRL inhibition at the end of lactation by bromocriptine (BRO) injection, a dopaminergic agonist, upon serum TSH and thyroid hormones, thyroid iodide uptake, liver mitochondrial a-glycerophosphate dehydrogenase (mGPD), liver and pituitary de-iodinase activities (D1 and/or D2), and in vitro post-TRH TSH release in the adult offspring. Wistar lactating rats were divided into BRO -injected with 1 mg/twice a day, daily for the last 3 days of lactation, and C -control, saline-injected with the same frequency. At 180 days of age, the offspring were injected with 125 I i.p. and after 2 h, they were killed. Adult animals whose mothers were treated with BRO at the end of lactation presented lower serum TSH (K51%), T 3 (K23%), and thyroxine (K21%), lower thyroid 125 I uptake (K41%), liver mGPD (K55%), and pituitary D2 (K51%) activities, without changes in the in vitro post-TRH TSH release. We show that maternal PRL suppression at the end of lactation programs a hypometabolic state in adulthood, in part due to a thyroid hypofunction, caused by a central hypothyroidism, probably due to decreased TRH secretion. We suggest that PRL during lactation can regulate the hypothalamus-pituitary-thyroid axis and programs its function.

“…Particularly, maternal nutritional and hormonal changes during the lactation period in rats were shown to program the thyroid function in adult life (Passos et al 2002, 2007, Dutra et al 2003, Lins et al 2005, Bonomo et al 2008. Since thyroid dysfunction is associated with marked changes on both energy expenditure and BW (Pontikides & Krassas 2007), it is interesting to evaluate the thyroid status in the model of programing by maternal NIC exposure during lactation.…”

Section: Introductionmentioning

confidence: 99%

Short- and long-term effects of maternal nicotine exposure during lactation on body adiposity, lipid profile, and thyroid function of rat offspring

Oliveira

Moura²,

Santos-Silva³

et al. 2009

Epidemiological studies show a higher prevalence of obesity in children from smoking mothers and smoking may affect human thyroid function. To evaluate the mechanism of smoking as an imprinting factor for these dysfunctions, we evaluated the programing effects of maternal nicotine (NIC) exposure during lactation. Two days after birth, osmotic minipumps were implanted in lactating rats, divided into: NIC (6 mg/kg per day s.c.) for 14 days; Control -saline. All the significant data were P!0 . 05 or less. Body weight was increased from 165 days old onwards in NIC offspring. Both during exposure (at 15 days old) and in adulthood (180 days old), NIC group showed higher total fat (27 and 33%). In addition, NIC offspring presented increased visceral fat and total body protein. Lipid profile was not changed in adulthood. Leptinemia was higher at 15 and 180 days old (36 and 113%), with no changes in food intake. Concerning the thyroid status, the 15-days-old NIC offspring showed lower serum-free tri-iodothyronine (FT 3 ) and thyroxine (FT 4 ) with higher TSH. The 180-days-old NIC offspring exhibited lower TSH, FT 3 , and FT 4 ). In both periods, liver type 1 deiodinase was lower (26 and 55%). We evidenced that NIC imprints a neonatal thyroid dysfunction and programs for a higher adiposity, hyperleptinemia, and secondary hypothyroidism in adulthood. Our study identifies lactation as a critical period to NIC programing for obesity, with hypothyroidism being a possible contributing factor.