Leptin, a potent anorexigenic hormone is found in the anterior pituitary. The aim of this study was to determine if and how pituitary leptin-bearing cells were regulated by nutritional status. Male rats showed 64% reductions in pituitary leptin mRNA, but not serum leptin, 24 h after fasting, accompanied by significant 30-50% reductions in growth hormone (GH), prolactin, luteinizing hormone (LH), and 70-80% reductions in target cells for gonadotropin releasing hormone (GnRH) or growth hormone releasing hormone (GHRH). There was a 2—fold increase in corticotropes. Subsets (22%) of pituitary cells co-expressed leptin and GH and <5% co-expressed leptin and LH, prolactin, TSH, or ACTH. Fasting resulted in significant 55-75% losses in cells with leptin proteins or mRNA and GH or LH. To determine if restoration of serum glucose could rescue leptin, LH and GH, additional fasted rats were given 10% glucose water for 24 h. Restoring serum glucose in fasted rats resulted in pituitary cell populations with normal levels of leptin, GH, and LH cells. Similarly, LH and GH cells were restored, in vitro, after populations from fasted rats were treated for as little as 1 h in 10-100 pg/ml leptin. These correlative changes in pituitary leptin, LH and GH, coupled with leptin’s rapid restoration of GH and LH, in vitro, suggest that pituitary leptin may signal nutritional changes. Collectively, the findings suggest that pituitary leptin expression could be coupled to glucose sensors like glucokinase, to facilitate rapid responses by the neuroendocrine system to nutritional cues.