FP01-3 GH Signaling in Vivo in Skeletal Muscle in Healthy Human Subjects: Impact of Gender and Age

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP01-Cell Specific GH & IGF-1 Signaling
Saturday, June 15, 2013: 11:00 AM-11:30 AM
Presentation Start Time: 11:10 AM
Room 134 (Moscone Center)

Poster Board SAT-89
Poul Vestergaard Nielsen1, Mikkel Holm Vendelbo2, Niels Moller3, Niels Jessen4 and Jens Otto Jorgensen*5
1Aarhus University Hospital, Denmark, 2Aarhus Univ Hospital, Ry, Denmark, 3Aarhus University Hospital, Aarhus C, Denmark, 4Aarhus University Hosp, Aarhus, Denmark, 5Aarhus Univ Hospital, Arhus C, Denmark
Background:  GH secretion and action depend on age and gender. Endogenous GH secretion declines with age, whereas elderly people are highly responsive to exogenous GH as judged by IGF-I generation and side effects. By contrast, endogenous GH secretion is amplified in females as compared to males, whereas females are relatively GH resistant as judged by IGF-I generation. The underlying mechanisms at the level of GH signaling in peripheral target tissues are unknown.

Aim: To study GH signaling in skeletal muscle in healthy human subjects as a function of age and gender.

Methods: Twenty healthy non-obese (BMI < 30 kg/m2) adults [‘young group’ < 40 yrs (5F/5M) and ‘elderly group’ > 60 yrs (5F/5M)] were each studied twice: 1) after iv. injection of a GH bolus (0.5 mg), and 2) iv. saline injection. Muscle biopsies were obtained after 30 and 120 min. Total and phosphorylated STAT5b were measured by WB and IGF-I and SOCS and CIS gene expression at t = 120 min. measured by RT-PCR. Body composition (DEXA) and VO2-max (bicycle) were also measured.

Results: The serum pharmacokinetic GH profile did not differ between groups. Phosphorylated STAT5b (pSTAT5b) was significantly increased in all subjects after GH with a maximum 30 min. post injections as compared to no change after saline. The mean ±SE pSTAT5b (AU) response to GH was more pronounced in women as compared to men [203.1±28 vs. 108.2±14.3 (P = 0.01)]. In addition, old women had a higher response as compared to young women and men of both ages (p=0.046). IGF-I mRNA expression increased after 120 min. in all groups but more so in the ‘young group’ (P=0.03). SOCS I-III and CIS mRNA expression increased significantly after 120 min. with no impact of age and gender. LBM correlated inversely with pSTAT5b at 30 min. (r=-0.56, P=0.01). The CIS mRNA response at 120 min was a positive determinant of pSTAT5b (P = 0.05).

Conclusion:  1) The relative GH resistance in females is located downstream of STAT5, 2) Old age is associated with a relative increase in GH responsiveness at the level of STAT5 activation, 3) Our model is  suited to provide mechanistic data regarding the impact of gender and age on GH responsiveness in human target tissues in vivo.

Nothing to Disclose: PVN, MHV, NM, NJ, JOJ

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

Sources of Research Support: Novo Nordisk Foundation