Regulation of murine skeletal muscle growth by STAT5B is age- and sex-specific.

Abstract

Background: Sexually dimorphic growth has been attributed to the growth hormone (GH)/insulin-like growth factor 1 (IGF1) axis, particularly GH-induced activation of the intracellular signal transducer and activator of transcription 5B (STAT5B), because deletion of STAT5B reduces body mass and the mass of skeletal muscles in male mice to that in female mice. However, it remains unclear why these effects are sex- and species-specific, because the loss of STAT5B retards growth in girls, but not in male mice. Our objectives were to determine whether sexually dimorphic growth of skeletal muscle persisted in STAT5B^-/- mice and investigate the mechanisms by which STAT5B regulates sexually dimorphic growth.

Methods: Blood and skeletal muscle were harvested from male and female STAT5B^-/- mice and their wild-type littermates from the onset of puberty to adulthood.

Results: Growth of the skeleton and skeletal muscles was retarded in both sexes of STAT5B^-/- mice, but more so in males. Although reduced, sexually dimorphic growth of skeletal muscle persisted in STAT5B^-/- mice with an oxidative shift in the composition of myofibres in both sexes. Concentrations of IGF1 in blood and skeletal muscle were reduced in male STAT5B^-/- mice at all ages, but only in female STAT5B^-/- mice at the onset of puberty. Expression of androgen receptor (AR) and oestrogen receptor alpha (ERα) mRNA and protein was reduced in skeletal muscles of male and female STAT5B^-/- mice, respectively. Loss of STAT5B abolished the sexually dimorphic expression of myostatin protein and Igf1, Ar, Erα, suppressor of cytokine signalling 2 (Socs2), and cytokine-inducible SH2-containing protein (Cis) mRNA in skeletal muscle.

Conclusions: STAT5B appears to mediate GH signalling in skeletal muscles of male mice at all ages, but only until puberty in female mice. STAT5B also appears to mediate the actions of androgens and oestrogens in both male and female mice, but sexually dimorphic growth persists in STAT5B^-/- mice.