The mechanism whereby undernutrition enhances the ability of estradiol (E) to inhibit reproductive activity is unknown. This study aimed to determine the effect of feed restriction on E receptor (ER)-containing cell numbers in the female sheep hypothalamus. Ovariectomized lambs at 7 months of age received either ad libitum (AL; n = 5) or restricted (FR; n = 10) levels of feed intake. Lambs were weighted weekly and FR lambs fed to lose approximately 15% of their initial body weights over 7 weeks, at the end of which jugular blood samples were collected at 10-min intervals for 5 h to assess the patterns of LH release. After blood collection, lambs were euthanized and hypothalami collected for immunocytochemical detection of ER. Based on LH secretory profiles, FR lambs were subdivided into two groups. The first group (FR + LH; n = 5) exhibited patterns of LH release similar to AL controls. LH secretion in the second group (FR-LH; n = 5) was obviously suppressed. Numbers of ER-containing cells did not differ significantly (p > 0.10) among treatment groups in the bed nucleus stria terminalis, anterior hypothalamic area and arcuate nucleus. ER-containing cell numbers were greater (p < 0.05) in the preoptic area (POA) but less (p < 0.05) in the ventromedial/ventrolateral hypothalamus (VMH/VLH) for FR-LH lambs compared to AL animals. Notably, for both the POA and VMH/VLH, ER-containing cell numbers in the FR + LH animals were intermediate and did not differ (p > 0.10) from either FR-LH or AL lambs. These results suggest that feed restriction differentially alters ER-containing cell numbers in specific regions of the ovine hypothalamus (numbers increased in the POA but decreased in the VMH/VLH). These changes may, at least in part, represent a mechanism whereby undernutrition enhances the ability of E to inhibit reproduction.

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