Anomalously rapid effect of the estrogen receptor- α agonist PPT on food intake in ovariectomized rats.

Abstract

Studies in knockout mice indicate that the feeding-inhibitory effect of estradiol (E2) requires the estrogen receptor alpha (ER-α). Consistent with that, Roesch [(2006) Physiological Behavior, 87, 39] reported that daily injections of the ER-α agonist PPT, but not the ER-α agonist DPN, reduces feeding in ovariectomized rats. However, whether PPT mimics the physiological effect of E2 on food intake is unknown. We therefore studied the effects of PPT, DPN and E2 on food intake in ovariectomized rats. Two microgram E2 benzoate was injected sc at mid-light once each 4th day, a near physiological regimen that decreases food intake and produces the cornified pattern of vaginal cytology typical of estrus 30–42 h later (i.e., during the second nocturnal phase after injection). Similarly timed injections of PPT (250 μg/rat) decreased food intake both at 6–18 and 30–42 h, i.e. during the first and second dark phase after injection. However, PPT produced vaginal cornification only at 30–42 h, i.e. at the same time as E2. DPN (100 μg/rat) did not change food intake at any time. The faster onset of inhibition of feeding after PPT in comparison to E2 indicates that PPT does not mimic the physiological effect of E2 on feeding and suggests that PPT's action on feeding may not depend on activation of nuclear ER-α. agonist PPT, but not the ER-α agonist DPN, reduces feeding in ovariectomized rats. However, whether PPT mimics the physiological effect of E2 on food intake is unknown. We therefore studied the effects of PPT, DPN and E2 on food intake in ovariectomized rats. Two microgram E2 benzoate was injected sc at mid-light once each 4th day, a near physiological regimen that decreases food intake and produces the cornified pattern of vaginal cytology typical of estrus 30-42 h later (i.e., during the second nocturnal phase after injection). Similarly timed injections of PPT (250 μg/rat) decreased food intake both at 6–18 and 30–42 h, i.e. during the first and second dark phase after injection. However, PPT produced vaginal cornification only at 30–42 h, i.e. at the same time as E2. DPN (100 μg/rat) did not change food intake at any time. The faster onset of inhibition of feeding after PPT in comparison to E2 indicates that PPT does not mimic the physiological effect of E2 on feeding and suggests that PPT's action on feeding may not depend on activation of nuclear ER-=.