Sex Hormones and the Selective Estrogen Receptor Modulator Tamoxifen Modulate Weekly Body Weights and Food Intakes in Adolescent and Adult Rats

This study documented the effect of changes in male and female sex hormones and the selective estrogen receptor modulator (SERM) tamoxifen on weight gain and food consumption of rats from puberty to adulthood, and assessed whether age at onset of treatment affected outcome. In Study 1, male and female WKY rats were either neutered or sham-operated before puberty, and a subgroup of neutered females underwent estrogen replacement (ERT) at the age of puberty. In Study 2, subgroups of neutered females received either ERT or tamoxifen beginning well into the postpuberty period. Weekly body weight and food consumption were assessed, and food consumption was normalized to metabolic weight (body weight 0.67 ). Neutering reduced the rate of weight gain in males (P < 0.05), but significantly increased it in females (P < 0.0001). ERT immediately reduced weight gain and prevented any further increase, resulting in weights below that of sham-operated females (P < 0.05). Tamoxifen prevented further weight gain and returned profiles to that of sham-operated females. Food consumption, normalized to metabolic weight, was similar in females and males, and both sexes showed a decrease through maturation to adulthood. Neutering decreased food consumption below that of sham-operated animals in both males and females (P < 0.05), and ERT returned it to sham levels. Despite the fact that tamoxifen had an effect on body weight similar to that of ERT, females receiving tamoxifen treatment consumed less food than both sham-operated and ERT females (P < 0.05). Weight gain is modulated by sex hormones in male and female rats, with both estrogen and tamoxifen exerting immediate effects in females, irrespective of the age at which treatment is initiated. Differences in food consumption do not appear to account for the effects of hormones and tamoxifen on body weight, suggesting that they exert a direct effect on overall body metabolism.