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

Abstract

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.

Effects of running wheel training on adult obese rats programmed by maternal prolactin inhibition

“…The inhibition of the production of maternal PRL may cause obesity in progeny via this mechanism; consequently, the inhibition of the production of PRL may impair the physical capacity of the progeny, as this inhibition is associated with other metabolic and hormonal alterations (such as changes in leptin levels and insulin resistance). Furthermore, the inhibition of the production of maternal PRL at the end of lactation induces a hypothyroidism in 180-day-old adult offspring (Bonomo et al 2008) that is related to low physical capacity (Zarzeczny et al 1996, Casimiro-Lopes et al 2008. However, previous work from our laboratory showed that animals in this model had higher exercise capacity at 90 days; this capacity returned to control levels at 180 days, even in animals with higher levels of VFM during both periods.…”

“…In the first model, we used a pharmacological approach to inhibit the production of maternal prolactin (PRL) with the dopamine agonist bromoa-ergocryptine (Bro). This method programs for obesity, hyperleptinemia, leptin resistance (Bonomo et al 2007), and hypothyroidism (Bonomo et al 2008), and symptoms (including insulin resistance and an altered lipid profile) are similar to those of metabolic syndrome (Moura et al 2009). More recently, we obtained a similar profile in adult animals with a non-pharmacological model where a maternal bandage was used to cover the teats of the dam in the late lactation, thus also inducing an early weaning of offspring (Lima et al 2011(Lima et al , 2013.…”

O desmame precoce afeta o ganho de peso e a composição corporal em camundongos adultos?

“…Desse modo, o desmame precoce e a consequente privação desses compostos presentes no leite materno podem ter influência sobre o risco de desenvolver obesidade na idade adulta [21][22][23][24][25] . Apesar de o efeito protetor do aleitamento materno em relação à adiposidade ser biologicamente plausível, os resultados obtidos em estudos epidemiológicos são inconsistentes.…”

“…Uma vez que o consumo de ração não diferiu entre os grupos, a diferença observada na massa corporal entre os animais amamentados e os animais desmamados precocemente pode ser atribuída à presença de fatores não nutricionais presentes no leite materno, a exemplo da leptina e do EGF, bem como a diferenças na resposta endócrina à alimentação (insulinemia pós-prandial) [15][16][17][18][19][20][21][22][23][24][25] . Nesse contexto, Attig et al 24 observaram que o tratamento com um antagonista da leptina entre o 2º e o 13º dia de vida resultou em um aumento significante do peso e da gordura corporal em ratos adultos.…”

“…Ademais, o presente estudo foi realizado em camundongos adultos jovens e, portanto, faz-se necessário investigar se o efeito do desmame precoce sobre a massa corporal persiste em fases mais avançadas da idade adulta [21][22][23][24][25] . Uma vez que os resultados deste estudo indicam que, em camundongos, o desmame precoce resulta em aumento do peso corporal, o que é decorrente de um aumento não apenas da massa gorda, como também da massa magra, é possível que estes resultados reproduzam-se em seres humanos.…”