Malnutrition during lactation is associated with hypoprolactinemia and failure in milk production. Adult rats whose mothers were malnourished presented higher body weight and serum tri-iodothyronine (T₃). 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 α-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 ¹²⁵I 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 (−51%), T₃ (−23%), and thyroxine (−21%), lower thyroid ¹²⁵I uptake (−41%), liver mGPD (−55%), and pituitary D2 (−51%) 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.

Maternal malnutrition during lactation reduces prolactin (PRL) and milk production, alters milk composition, and programs the body weight of the offspring. Our study aimed to evaluate the long-term effects of maternal hypoprolactinemia at the end of lactation on food ingestion, body weight, amount of retroperitoneal white adipose tissue (RPWAT), leptinemia, and anorectic leptin effect in the adult offspring. Lactating rats were treated with bromocriptine (BRO), a PRL inhibitor, 1 mg twice a day, or saline (C – control) for the last 3 days of lactation. The body weight and food intake were monitored, and after sacrifice at 180 days, the RPWAT was weighted. In a second experiment, the anorectic leptin effect was tested on 180-day-old animals. Adult offspring whose mothers were BRO-treated showed higher body weight (10%), higher amount of RPWAT (2.3 times), higher total body fat (+39%), and hyperleptinemia (2.9 times) when compared with C, although food intake did not alter. After injection of leptin, the food ingestion at 2, 4 and 6 h was unaffected in BRO animals, confirming a resistance to the anorectic effect of leptin. Since the maternal PRL inhibition during lactation programs, a higher body weight with no alteration of food ingestion, we suggest a hypometabolic state. The leptin anorectic resistance can be due to the hyperleptinemia. We suggest that PRL changes during lactation can regulate body weight during adulthood.

Resveratrol (Res) has been associated with protective effects against oxidative stress. This study evaluated the effect of Res over lipid peroxidation, antioxidant defense, hepatic sirtuin 1 (SIRT1), which up-regulates antioxidant enzymes, and copper/zinc superoxide dismutase (Cu/Zn SOD) in adult offspring whose mothers were protein restricted during lactation. Lactating Wistar rats were divided into control (C) group, which were fed a normal diet (23% protein), and low-protein and high-carbohydrate (LPHC) group, which were fed a diet containing 8% protein. After weaning (21 days), C and LPHC offspring were fed a normal diet until they were 180 days old. At the 160th day, animals were separated into four groups as follows: control, control+Res, LPHC, and LPHC+Res. Resveratrol was given for 20 days (30 mg/kg per day by gavage). LPHC animals showed a higher total antioxidant capacity (TAC) without change in lipid peroxidation and SIRT1 expression. The treatment with Res increased TAC only in the control group without effect on lipid peroxidation and SIRT1. LPHC animals treated with Res had lower lipid peroxidation and higher protein and mRNA expression of SIRT1 without any further increase in TAC. No significant difference in liver Cu/Zn SOD expression was observed among the groups. In conclusion, maternal protein restriction during lactation programs the offspring for a higher antioxidant capacity, and these animals seem to respond to Res treatment with a lower lipid peroxidation and higher hepatic SIRT1 expression that we did not observe in the Res-treated controls. It is probable that the protective effect can be attributed to Res activating SIRT1, only in the LPHC-programed group.