Naslov
Intermittent recombinant TSH injections prevent ovariectomy-induced bone loss

Autori
Sun, L ; Vukičević, Slobodan ; Baliram, R ; Yang, G ; Sendak, Rebecca ; McPherson, J ; Zhu, LL ; Iqbal, J. ; Latif, R. ; Natrajan, A. ; Arabi, A. ; Yamoah, K. ; Moonga, B. S. ; Gabet, Y. ; Davies, T. F. ; Bab, I. ; Abe, E. ; Sampath, T. Kuber ; Zaidi, Mone

Izvornik
Proceedings of the National Academy of Sciences of the United States of America (0027-8424) 105 (2008), 11; 4289-4294

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
osteoclast; osteoporosis; pituitary; osteoblast; bisphosphonate

Sažetak
We recently described the direct effects of thyroid-stimulating hormone (TSH) on bone and suggested that the bone loss in hyperthyroidism, hitherto attributed solely to elevated thyroid hormone levels, could at least in part arise from accompanying decrements in serum TSH. Recent studies on both mice and human subjects provide compelling evidence that thyroid hormones and TSH have the opposite effects on the skeleton. Here, we show that TSH, when injected intermittently into rodents, even at intervals of 2 weeks, displays a powerful antiresorptive action in vivo. By virtue of this action, together with the possible anabolic effects shown earlier, TSH both prevents bone loss and restores the lost bone after ovariectomy. Importantly, the osteoclast inhibitory action of TSH persists ex vivo even after therapy is stopped for 4 weeks. This profound and lasting antiresorptive action of TSH is mimicked in cells that genetically overexpress the constitutively active ligand-independent TSH receptor (TSHR). In contrast, loss of function of a mutant TSHR (Pro Leu at 556) in congenital hypothyroid mice activates osteoclast differentiation, confirming once again our premise that TSHRs have a critical role in regulating bone remodeling.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

POVEZANOST RADA