Fasting and Glucose Effects on Pituitary Leptin Expression: Is Leptin a Local Signal for Nutrient Status?
Christopher Crane 1, Noor Akhter 1, Brandy W. Johnson 1, Mary Iruthayanathan 1, Farhan Syed 1, Akihiko Kudo 1, Yi-Hong Zhou 1 and Gwen V. Childs 1*
1 Department of Neurobiology and Developmental Sciences, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas (CC,NA,BWJ,FS,GVC); Department of Anatomy, Kyorin University School of Medicine, Tokyo, Japan (AK); Division of Endocrinology, Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, Iowa (MI); and Department of Neurological Surgery, University of California Irvine, Orange, California (Y-HZ)
* To whom correspondence should be addressed. E-mail: childsgwenv{at}uams.edu.
Submitted on February 19, 2007
Accepted on 5 June 2007
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Abstract |
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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 leptins 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.