Food Availability Affects Neural Estrogen Receptor Immunoreactivity in Prepubertal Mice

Abstract

How underfeeding delays maturation of the central mechanisms affecting GnRH release at the onset of puberty, and why females are more sensitive to underfeeding than males are not well understood. We tested the hypothesis that the sexually dimorphic effects of underfeeding on GnRH release are mediated in part through the estrogen receptor (ER). We investigated the influence of underfeeding on the number of ER-immunoreactive (ER-ir) cells in the medial preoptic area (mPOA), ventromedial nucleus (VMN), and arcuate nucleus (ARH) of prepubertal CF-1 mice, neural areas known to influence GnRH release. In females, 7 days of underfeeding reduced detectable ER-ir cells in the mPOA and VMN, but not in the ARH. Also, we noted a direct relationship between the percent body weight change the last 24 h before perfusion and the numbers of ER-ir cells in the mPOA (r = 0.69; P = 0.0008) and VMN (r = 0.56; P = 0.01). In males, 17 days of underfeeding did not affect ER-ir cell numbers in any region. A subsequent investigation of the time course of alterations in ER immunoreactivity revealed that in female mice ER-ir cell numbers were reduced within 48 h of underfeeding in the mPOA, VMN, and ARH. ER-ir cell number was not changed in male mice. When female mice were underfed for 48 h and then refed, ER-ir cell numbers normalized by 24 h in the mPOA, VMN, and ARH. For the time-course experiments, the percent body weight change the last 24 h before perfusion and the number of ER-ir cells were related in the mPOA (r = 0.47; P < 0.001) and VMN (r = 0.49; P < 0.001), but not in the the ARH (r = 0.23; P < 0.12) in female mice, and in the mPOA (r = 0.66; P < 0.001), VMN (r = 0.33; P = 0.06), and ARH (r = 0.45; P = 0.007) in male mice. Thus, despite no significant change in ER-ir cell number in the male mice, there was a relationship between the percent body weight change during the last 24 h before perfusion and the number of ER-ir cells. We conclude that in male mice, correlation analyses between the percent body weight change before perfusion and ER-ir cell number may be a more sensitive marker of the metabolic condition at the time of perfusion. In female mice, underfeeding may stall puberty by reducing the number of ER-ir cells in brain areas important for signal transmission of GnRH release.