TitleRole of estrogen receptor signaling in skeletal response to leptin in female mice.
Publication TypeJournal Article
Year of Publication2017
AuthorsTurner, RT, Philbrick, KA, Kuah, AF, Branscum, AJ, Iwaniec, UT
JournalJ Endocrinol
Date Published06/2017
KeywordsAnimals, Bone Density, Bone Development, Female, Leptin, Mice, Osteogenesis, Receptors, Estrogen, Signal Transduction

Leptin, critical in regulation of energy metabolism, is also important for normal bone growth, maturation and turnover. Compared to wild type (WT) mice, bone mass is lower in leptin-deficient mice. Osteopenia in growing mice is due to decreased bone accrual, and is associated with reduced longitudinal bone growth, impaired cancellous bone maturation and increased marrow adipose tissue (MAT). However, leptin deficiency also results in gonadal dysfunction, disrupting production of gonadal hormones which regulate bone growth and turnover. The present study evaluated the role of increased estrogen in mediating the effects of leptin on bone in mice. Three-month-old female mice were randomized into one of the 3 groups: (1)  + vehicle (veh), (2)  + leptin (leptin) or (3)  + leptin and the potent estrogen receptor antagonist ICI 182,780 (leptin + ICI). Age-matched WT mice received vehicle. Leptin (40 µg/mouse, daily) and ICI (10 µg/mouse, 2×/week) were administered by subcutaneous injection for 1 month and bone analyzed by X-ray absorptiometry, microcomputed tomography and static and dynamic histomorphometry. Uterine weight did not differ between mice and mice receiving leptin + ICI, indicating that ICI successfully blocked the uterine response to leptin-induced increases in estrogen levels. Compared to leptin-treated mice, mice receiving leptin + ICI had lower uterine weight; did not differ in weight loss, MAT or bone formation rate; and had higher longitudinal bone growth rate and cancellous bone volume fraction. We conclude that increased estrogen signaling following leptin treatment is dispensable for the positive actions of leptin on bone and may attenuate leptin-induced bone growth.

Alternate JournalJ. Endocrinol.
PubMed ID28428364
PubMed Central IDPMC5527997
Grant ListR01 AR060913 / AR / NIAMS NIH HHS / United States