Estradiol decreases the orexigenic effect of neuropeptide Y, but not agouti-related protein, in ovariectomized rats

Abstract

Available data suggest that estradiol exerts an inhibitory effect on food intake by modulating the actions of multiple gut- and brain-derived peptides implicated in the control of food intake. For example, recent studies have shown that estradiol decreases the orexigenic effects of ghrelin and melanin-concentrating hormone. In the present study, we examined estradiol's ability to decrease the actions of two additional orexigenic peptides, neuropeptide Y (NPY) and agouti-related protein (AgRP). Food intake was monitored following lateral ventricular infusions of 5 microg NPY, 10 microg AgRP, or saline vehicle in ovariectomized rats treated with either 1 microg estradiol or sesame oil vehicle. NPY increased food intake for 2h in both oil- and estradiol-treated ovariectomized rats. During this interval, the orexigenic effect of NPY was significantly greater in oil-treated rats, relative to estradiol-treated rats. In contrast to the short-term action of NPY, a single injection of AgRP increased food intake for 3 days in oil- and estradiol-treated rats. Meal pattern analysis revealed that the orexigenic effect of AgRP is mediated by an increase in meal size, not meal number. Unlike that observed following NPY treatment, estradiol failed to modulate the magnitude by which AgRP increased food intake and meal size. We conclude that a physiological regimen of estradiol treatment decreases the orexigenic effect of NPY, but not AgRP, in ovariectomized rats.

Fig. 1

The orexigenic effect of NPY is decreased by estradiol treatment in OVX rats. Oil- and estradiol-treated rats received intracerebroventricular infusions of 5 µg NPY or saline vehicle during the mid-light phase. Analysis of food intake during the following 24 h interval revealed that the orexigenic effect of NPY was limited to the first 2 h following drug treatment. During this interval, the orexigenic effect of NPY was greater in oil-treated rats, relative to estradiol-treated rats. *Greater than saline-treated rats, P < 0.05. ⁺Oil/NPY group greater than estradiol/NPY group, P < 0.05.

Fig. 2

The orexigenic effect of AgRP is not influenced by estradiol treatment in OVX rats. Oil-and estradiol-treated rats received intracerebroventricular infusions of 10 µg AgRP or saline vehicle during the mid-light phase. During the first day following drug treatment, AgRP produced a similar increase in food intake in oil- and estradiol-treated rats. A main effect of hormone treatment also revealed that food intake was reduced in estradiol-treated rats, relative to oil-treated rats. *Greater than saline-treated rats, P < 0.01. ⁺Estradiol-treated rats less than oil-treated rats, P < 0.05.

Fig. 3

The orexigenic effect of AgRP is mediated by an increase in meal size, not meal number, in oil- and estradiol-treated OVX rats. (A) During the first day following drug treatment, AgRP induced a similar increase in average meal size in oil- and estradiol-treated rats. A main effect of hormone treatment also revealed that average meal size was reduced in estradiol-treated rats, relative to oil-treated rats. (B) AgRP failed to alter meal number in either oil- or estradiol-treated rats. *Greater than saline-treated rats, P < 0.05. ⁺Estradiol-treated rats less than oil-treated rats, P < 0.05.