Thyroxine modifies the effects of growth hormone in Ames dwarf mice.
Ames dwarf (df/df) mice lack growth hormone (GH), thyroid stimulating hormone and prolactin. Treatment of juvenile df/df mice with GH alone stimulates somatic growth, reduces insulin sensitivity and shortens lifespan. Early-life treatment with thyroxine (T4) alone produces modest growth stimulation but does not affect longevity. In this study, we examined the effects of treatment of juvenile Ames dwarf mice with a combination of GH + T4 and compared them to the effects of GH alone. Treatment of female and male dwarfs with GH + T4 between the ages of 2 and 8 weeks rescued somatic growth yet did not reduce lifespan to match normal controls, thus contrasting with the previously reported effects of GH alone. While the male dwarf GH + T4 treatment group had no significant effect on lifespan, the female dwarfs undergoing treatment showed a decrease in maximal longevity. Expression of genes related to GH and insulin signaling in the skeletal muscle and white adipose tissue (WAT) of female dwarfs was differentially affected by treatment with GH + T4 vs. GH alone. Differences in the effects of GH + T4 vs. GH alone on insulin target tissues may contribute to the differential effects of these treatments on longevity.
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA.
Andrew
A
Do
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA.|Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina Columbia, SC 29209, USA.
Vinal
V
Menon
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA.|Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
Xu
X
Zhi
Department of Oncological Endocrinology, Medical University of Lodz, 90-752 Lodz, Poland.
Adam
A
Gesing
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA.|Department of Medical Biochemistry and Molecular Biology, University of Saarland, 66421 Homburg, Germany.|Department of Biotechnology, University of Applied Sciences Kaiserslautern, 66482 Zweibrücken, Germany.
Denise S
DS
Wiesenborn
Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62794, USA.
Adam
A
Spong
Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62794, USA.
Liou
L
Sun
Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62794, USA.
Andrzej
A
Bartke
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA.|Department of Head and Neck Surgery, The Greater Poland Cancer Centre, 61-866 Poznan, Poland.
Michal M
MM
Masternak
D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D004347:Drug Interactions; D004392:Dwarfism / Q000188:drug therapy*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D013006:Growth Hormone / Q000494:pharmacology / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008136:Longevity / Q000187:drug effects*; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013974:Thyroxine / Q000494:pharmacology / Q000627:therapeutic use*
D013006:Growth Hormone; D013974:Thyroxine