Developmental plasticity in adrenal function and leptin production primed by nicotine exposure during lactation: gender differences in rats.

Neonate male rats whose mothers were nicotine-treated during lactation have higher adiposity, hyperleptinemia, and adrenal dysfunction. At adulthood, they still present higher adiposity and hyperleptinemia, but there was no report about their adrenal function. Also, there was no report of this developmental plasticity on females. Here, we evaluated the adrenal function and leptin content in adipocytes and muscle of male and female adult offspring whose mothers were nicotine-treated during lactation. On the 2nd postnatal day (PN2), dams were subcutaneously implanted with osmotic minipumps releasing nicotine (NIC-6 mg/kg/day) or saline for 14 days (12 litters/group and 2 rats/litter). Male and female offspring were killed on PN180. Significant data were p<0.05. Male NIC offspring presented higher adrenal catecholamine content (+ 89%) and TH expression (+ 38%), lower "in vitro" catecholamine release (- 19%), and higher adrenergic ß3 receptor (ADRB3, + 59%) content in visceral adipose tissue (VAT). Serum corticosterone was higher (+ 77%) in male NIC group, coherent with the increase of both CRH and ACTH immunostaining in hypothalamus and pituitary, respectively. Leptin content was higher in VAT (+ 23%), which may justify the observed hyperleptinemia. Female NIC offspring presented lower ADRB3 content in VAT (- 39%) and lower leptin content in subcutaneous adipose tissue (SAT) (- 46%), but higher leptin content in soleus muscle (+ 22%), although leptinemia was normal. We evidenced a sex dimorphism in the model of maternal nicotine exposure during lactation. The adrenal function in adult offspring was primed only in male offspring while the female offspring displayed relevant alterations in leptin content on muscle and adipocytes.