Pituitary-derived leptin regulates somatotropes and contributes to the postnatal leptin surge

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 142-166-Hypothalamus-Pituitary Development & Biology
Basic/Clinical
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-146
Angela Katherine Odle*, Melody Lyn Allensworth, Anessa Haney and Gwen V Childs
University of Arkansas for Medical Sciences, Little Rock, AR
Leptin is a circulating hormone produced by white fat cells, the pituitary, and several other tissues that is best known for its role in appetite and energy regulation. Mice exhibit a surge in circulating leptin occurring between postnatal days (PND) 7-10 that decreases to adult leptin levels before the onset of puberty. This surge occurs independent of an increase in body mass and does not regulate food intake or energy expenditure before PND 14 (1). The pituitary itself produces leptin during postnatal development, peaking around PND 4. The major leptin-producing cell type in the pituitary is the somatotrope, which requires leptin for optimal maintenance (2,3). We hypothesize that leptin produced by the pituitary contributes to the leptin surge and is important for the normal development of the somatotrope. To test this hypothesis, we created animal models in which floxed leptin exon 3 is knocked out either only in the pituitary (Cre-GHRHr) or only in white fat cells (Cre-Adipoq).  We collected serum and pituitary cells from control and mutant pups at PND 1, 4, 7, 10, 14, 18, 21 and adults. Both control and mutant mice in the Cre-GHRHr line show a postnatal leptin surge, however the mutant males and females have an uncharacteristic dip 4-7 days before the peak. Additionally, the peak in mutants appears later (PND14) than the control peak (PND10). As expected, the mutant Cre-Adipoq line has no serum leptin, even in postnatal samples taken during the time of the leptin surge. Cre-GHRHr mutant males have significantly lower % of cells immunolabeled for leptin (6±2) or GH (16±2) compared to controls (35±3% leptin; 31±1% GH cells) (p<0.0016).  Adult males (4MO) from this line have significantly lower serum leptin levels than controls (CTL: 3937pg/mL ± 854.8pg N=3, DEL: 841.0pg/mL ± 328.9pg N=3, p<0.04) despite no significant difference in body weights. Adult male (6 MO) mutants from the Cre-Adipoq line have significantly higher % leptin cells (CTL: 35.3% ± 1.5% N=4, DEL: 45.6% ± 3.2% N=5, p<0.02), suggesting that the pituitary may be compensating for a lack of circulating leptin. The percentages of GH cells are not different from control values, which is interesting since the 6 MO Adipoq mutant males are obese (CTL: 35.25g ± 1.7g N=2, DEL: 76.32g ± 3.8g N=5, p<0.0005). Thus, even in the absence of the body’s major source of leptin, the pituitary source appears to be sufficient to maintain the population of GH cells, which are reduced when pituitary leptin is ablated. In addition, these studies suggest that pituitary leptin-bearing cells are capable of altering the shape and timing of the neonatal leptin surge, and that they add to adult serum leptin. Future studies will further characterize the consequences of pituitary leptin loss to the somatotropes, including the potential for GH deficiency and possible metabolic deficits.

(1)  Mistry et al., Organogenesis 1999; 277:R742-7 (2)  Childs et al., Endocrinology 2011; 152:69(4) (3) Akhter et al., Endocrinology 2012; 153:4705

Nothing to Disclose: AKO, MLA, AH, GVC

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: NIH Grant R01 HD-059056; NIH Grant R03 HD059066; Molecular Core-COBRE P20 GM103425; and Core facilities in P30 NS047546