Effects of estradiol on immediate early gene expression associated with ovulation in lactating rats: role of nutritional status

Abstract

In rats, food restriction during lactation extends lactational infertility, an effect that is in part due to attenuated luteinizing hormone (LH) responses to the positive feedback effects of estradiol (E2). In cycling rats, rising endogenous E2 levels not only induce a surge in LH release, but also increase the expression of the immediate early gene Fos in the anteroventral preoptic area (AVPV) and within gonadotropin releasing hormone (GnRH) neurons. This experiment examined whether the induction of Fos expression in the AVPV and within GnRH neurons after E2 treatment varied with stage of lactation and nutritional status. Brains of estrogen-treated ad lib fed and food-restricted lactating rats were processed for Fos or Fos/GnRH immunocytochemistry on days 15, 20, or 25 postpartum (pp). Cell counts from both labeling studies showed that on day 15 pp, neuronal activation in the AVPV and within GnRH neurons was low and did not differ between ad lib fed and food-restricted dams. On day 20 pp, levels of Fos-like immunoreactivity (FOS-IR) in the AVPV remained low in all dams but were significantly higher in ad lib fed dams. By day 25 pp, the ability of E2 to induce FOS-IR in the AVPV of food-restricted dams remained compromised. The proportion of GnRH cells expressing FOS-IR following E2 stimulation was restored to baseline levels by day 20 pp regardless of the nutritional status of the dam. These results show that the effects of E2 on neuronal events that correlate with the LH surge, are attenuated during lactation. Furthermore, food restriction during lactation selectively alters neuronal activation in the AVPV suggesting that this area integrates nutritional information to regulate LH release.