Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2015) 37 GP18.03 | DOI: 10.1530/endoabs.37.GP.18.03

ECE2015 Guided Posters Pituitary–Basic and IGF-1 (9 abstracts)

Regulation of sexually dimorphic growth of murine skeletal muscle by Stat5a and Stat5b

Ryan Paul 1, , Marianne Elston 1 , John Conaglen 1 & Chris McMahon 2


1Department of Medicine, Waikato Clinical School, University of Auckland, Hamilton, New Zealand; 2AgResearch, Ruakura, New Zealand.


GH regulates IGF1 predominantly through the intracellular signallers Stat5a and Stat5b. Inactivating mutations of Stat5b in humans result in severe growth retardation and low circulating IGF1 concentrations in males and females. In mice, however, there is only a loss of sexually dimorphic growth in males when Stat5b is deleted. No study has observed Stat5b−/− mice beyond 12 weeks or investigated any subsequent changes in skeletal muscle mass or IGF1 expression. Blood and hindlimb muscles of male and female Stat5b−/− mice and WT littermates were collected at 6, 12, and 24 weeks of age (n=16/time and sex). Plasma IGF1 and IGF1 protein concentrations were determined by ELISA and muscle mass was normalised to bone length. C2C12 myoblast cell lines were treated with viral Stat5b siRNA and/or Stat5a siRNA or a scrambled vector (control), then differentiated and treated with GH (100 ng/ml) for 24 h. RNA was harvested for quantitative PCR. The treated cell lines were also treated for 96 h with GH (100 ng/ml) and differentiation was assessed by immunocytochemistry. Sexual dimorphism was reduced, but persisted in Stat5b−/− mice. Nasoanal length, tibia length and normalised hindlimb muscle mass were decreased to a greater extent in male (23%) than in female (14%) Stat5b−/− mice at all ages (P<0.001). Concentrations of IGF1 in plasma and skeletal muscle were significantly reduced in male Stat5b−/− mice at all ages and in female Stat5b−/− mice at 6 weeks. Stat5a knockdown inhibited myotube differentiation (36%) to a lesser extent than Stat5b or dual Stat5a/5b knockdown (80%) (P<0.001). Either Stat5a or Stat5b knockdown prevented the GH-induced myotube hypertrophy, but only Stat5a knockdown blocked the upregulation of IGF1 mRNA by GH. We conclude that both Stat5a and Stat5b have independent roles in GH signaling in murine skeletal muscle.

Disclosure: Waikato Medical Research Foundation (grant number 223).

Article tools

My recent searches

No recent searches.