Leptin's Regulatory Role in Neonatal Development of Somatotropes

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 88-108-GHRH, GH & IGF Biology & Signaling
Basic/Translational
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-104
Melody Lyn Allensworth*, Angela Katherine Odle, Anessa Haney and Gwen V Childs
University of Arkansas for Medical Sciences, Little Rock, AR
Somatotropes differentiate and are maintained throughout life under the influence of a variety of regulatory hormones, including glucocorticoids, ghrelin, growth hormone releasing hormone, and leptin. Different hormonal influences predominate during each stage of development. Mice lacking leptin or leptin receptors show reduced numbers of somatotropes. Because serum leptin levels surge between postnatal days (pnd) 7 and 10, we hypothesized that leptin might stimulate postnatal expansion of the somatotrope population. To test this hypothesis, we deleted LEPR exon 1 selectively in somatotropes, which removes all isoforms of the receptor (1). After proving selective deletion of LEPR only in the pituitary, we studied mutants and littermate controls at pnd 1, 5, 10 and 15, and 4 months. In adult mutants, the percentage of immunolabeled GH cells and serum GH were reduced significantly (2). In contrast, neonate mutants had serum GH levels similar to those of controls. In both groups, serum GH was highest on day 1 (111 ± 66 ng/ml control n=7; 98.6 ± 60 ng/ml mutants n=8) followed by a sharp reduction to 3.96 ± 2.9 ng/ml, controls and 5.6 ± 4.6 ng/ml, mutants by day 15. There were no sex differences in any age group. When immunolabeled GH cells were counted in freshly dispersed cultures, control mice showed a significant increase from 5-10d of age (5d: 39% males; 24% females; 10d 42% males; 45% females, p<0.01). In contrast, mutant males showed reduced % GH cells and no increase with age (5d 20%; 10d 23%; 15d 23%). Mutant females showed a slight increase in % GH cells with age (5d 14%; 10d 24%; 15d 28% p<0.007). In spite of the similarity in serum GH between mutants and controls, the percentages of GH cells in mutants are significantly lower than those in control cultures in all age groups. This suggests that leptin is important for full expression of GH stores in developing somatotropes, but the cells are still able to maintain serum levels like those of their littermate controls. They may have differentiated normally due to the known regulatory effects of other hormones early in development, such as glucocorticoids and ghrelin. These data indicate that the developing mutants are not yet GH deficient based on serum data, however leptin’s optimization of GH stores is deficient as early as 5 days of age. Our previous studies showed that selective ablation of leptin receptors in somatotropes eventually leads to GH deficiency in the adult, with obesity and metabolic consequences (2-4).

(1) Cohen et al., J Clin Invest 2001; 108:1113(2) Allensworth et al., Abstract #MON137, p153; 2012 Endocrine Society meetings(3) Childs et al., Endocrinology 2011; 152:69(4) Akhter et al., Endocrinology 2012; 153:4705

Nothing to Disclose: MLA, AKO, 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.