Corticotropin releasing factor receptor type II (CRF2) messenger ribonucleic acid levels in the hypothalamic ventromedial nucleus of the infant rat are reduced by maternal deprivation

Abstract

The stress neurohormone corticotropin releasing factor (CRF) activates at least two receptor types. Expression of corticotropin releasing factor receptor type II (CRF2) has been demonstrated in the hypothalamic ventromedial nucleus (VMH) of the adult and developing rat, but the physiological functions of VMH-CRF2 have not been elucidated. The VMH has been documented as an important participant in the regulation of food intake and its interactions with the hypothalamic-pituitary-adrenal axis and circadian rhythms. Regulation of VMH-CRF2 may thus play a role in the interplay of physiological alterations in metabolic state with the neuroendocrine and anorexic effects of CRF. This study determined the regulation of CRF2-mRNA expression in infant rats by the physiological consequences of maternal deprivation, i.e., fasting and stress. Using in situ hybridization, maternally deprived pups had an average 62% reduction of VMH-CRF2-mRNA levels compared with stress-free controls. Maternal deprivation also resulted in elevated plasma corticosterone levels (3.8 +/- 0.3 vs. 1.3 +/- 0.1 microg/dl) and an average 5.7% body weight loss. This study demonstrates that maternal deprivation, via fasting and HPA activation, leads to a dramatic decrease of CRF2-mRNA levels in the VMH. These results are consistent with a role for CRF2 activation in mediating some of the complex interactions of CRF (or urocortin) with regulation of food intake in the developing rat.

Fig. 1

Elevation of basal plasma corticosterone (CORT) levels in maternally deprived 9 day old rats. 24h of maternal deprivation resulted in a significant increase (p<0.0001) in morning plasma CORT levels compared with non maternally deprived controls.

Fig. 2

Computer analyzed false color images showing CRF₂ - mRNA levels in the VMH of stress-free (control) and maternally deprived rats. Red and yellow colors represent maximum ³⁵S riboprobe density as shown in the scale.

Fig. 3

Semiquantitative analysis of CRF₂-mRNA expression within the VMH of maternally deprived rats. Bars represent the mean CRF₂-mRNA expression in the VMH of 9 day old rats maternally deprived for 24h or non-maternally deprived controls with error bars illustrating the standard error of the mean. A significant decrease in CRF₂-mRNA abundance was observed as a consequence of maternal deprivation (p<0.005).