Follicle-stimulating hormone does not impact male bone mass in vivo or human male osteoclasts in vitro.
Bone loss in the elderly is mainly caused by osteoclast-induced bone resorption thought to be causally linked to the decline in estrogen and testosterone levels in females and males. Recently, involvement of follicle stimulating-hormone (FSH) in this process has been suggested to explain in part the etiology of the disease in females, whereas its role in males has never been examined. In this study, the direct impact of FSH on bone mass of 16-week-old C57BL/6J male mice by either daily intermittent application of 6 or 60 mug/kg of FSH or continuous delivery via miniosmotic pump of a dose of 6 mug/kg over the course of a month was assessed. Femoral peripheral quantitative computed tomographic and microcomputed tomographic analyses at 0, 2, and 4 weeks of FSH-treated mice did not reveal any differences in cancellous and cortical bone compared to sham-treated mice. FSH functionality was verified by demonstrating cAMP induction and activation of a cAMP-response element-containing reporter cell line by FSH. Furthermore, osteoclastogenesis from human mononuclear cell precursors and from RAW 264.7 cells was not affected by FSH (3, 10, 30 ng/mL) compared to control. No direct effect of FSH on gene regulation was observed by Affymetrix Gene Array on RAW 264.7 cells. Lastly, no expression of FSH receptor (FSHR) mRNA or FSHR was observed by quantitative polymerase chain reaction and Western blot in either human male osteoclasts or RAW 264.7 cells. These data show that FSH does not appear to modulate male bone mass regulation in vivo and does not act directly on osteoclastogenesis in vitro.
Ritter
Veronique
V
Musculoskeletal Disease Area, Novartis Institutes for Biomedical Research, Basel, Switzerland.
Thuering
Barbara
B
Saint Mezard
Pierre
P
Luong-Nguyen
Ngoc-Hong
NH
Seltenmeyer
Yves
Y
Junker
Uwe
U
Fournier
Brigitte
B
Susa
Mira
M
Morvan
Frederic
F
D000328:Adult; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015918:Infusion Pumps, Implantable; D007263:Infusions, Parenteral; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011962:Receptors, FSH / Q000235:genetics / Q000378:metabolism; D014057:Tomography, X-Ray Computed
D017362:Cyclic AMP Response Element-Binding Protein; D012333:RNA, Messenger; D011962:Receptors, FSH; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP