A molecular basis for the sexually dimorphic response to growth hormone.
Once reserved solely for the treatment of short stature, the now readily available recombinant GH has expanded the use of the hormone to include the treatment of cardiovascular, renal, muscular, skeletal, immunological, psychosocial, and metabolic abnormalities associated with GH deficiency. There are also proposals for the widespread use of the hormone to ameliorate or reverse aging. However, this extensive use of GH has revealed intrinsic sexual dimorphisms in which females are considerably less responsive to the therapeutic regimen than are males. Dynamic changes in the Janus kinase-2 (Jak2)/signal transducers and activators of transcription (Stat5B) signaling pathway [as determined by transducer activation, Stat5B binding to the GH-responsive promoter of the CYP2C11 gene, and expression levels of the suppressors of cytokine signaling family (Socs2, Socs3, and Cis)] were examined in male and female rat-derived primary hepatocyte cultures exposed to the masculine-like episodic GH profile. We report that the cellular actions of GH normally mediated by activation of the Jak2/Stat5B pathway are suppressed in female cells possibly due to an inherent overexpression of Cis, a member of the suppressors of cytokine signaling family that normally down-regulates the Jak2/Stat5B pathway.
Thangavel
Chellappagounder
C
Laboratories of Biochemistry, University of Pennsylvania School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, PA 19104-6048, USA.
Shapiro
Bernard H
BH
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D000072467:Cytochrome P450 Family 2; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D013006:Growth Hormone / Q000494:pharmacology / Q000502:physiology*; D007016:Hypophysectomy; D053614:Janus Kinase 2 / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051381:Rats; D050799:STAT5 Transcription Factor / Q000378:metabolism; D012727:Sex Characteristics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D039181:Steroid 16-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics
D001189:Aryl Hydrocarbon Hydroxylases; D000072467:Cytochrome P450 Family 2; D013006:Growth Hormone; D053614:Janus Kinase 2; D050799:STAT5 Transcription Factor; D039181:Steroid 16-alpha-Hydroxylase; D050826:Suppressor of Cytokine Signaling Proteins; C494094:Stat5a protein, rat; C494097:Stat5b protein, rat; C450279:CYP2C11 protein, rat; C507927:Jak2 protein, rat