FSH-receptor isoforms and FSH-dependent gene transcription in human monocytes and osteoclasts.
Cells of the monocyte series respond to follicle stimulating hormone (FSH) by poorly characterized mechanisms. We studied FSH-receptors (FSH-R) and FSH response in nontransformed human monocytes and in osteoclasts differentiated from these cells. Western blot and PCR confirmed FSH-R expression on monocytes or osteoclasts, although at low levels relative to ovarian controls. Monocyte and osteoclast FSH-Rs differed from FSH-R from ovarian cells, reflecting variable splicing in exons 8-10. Monocytes produced no cAMP, the major signal in ovarian cells, in response to FSH. However, monocytes and osteoclasts transcribed TNFalpha in response to the FSH. No relation of expression of osteoclast FSH-R to the sex of cell donors or to exposure to sex hormones was apparent. Controls for FSH purity and endotoxin contamination were negative. Unamplified cRNA screening in adherent CD14 cells after 2h in 25ng/ml FSH showed increased transcription of RANKL signalling proteins. Transcription of key proteins that stimulate bone turnover, TNFalpha and TSG-6, increased 2- to 3-fold after FSH treatment. Smaller but significant changes occurred in transcripts of selected signalling, adhesion, and cytoskeletal proteins. We conclude that monocyte and osteoclast FSH response diverges from that of ovarian cells, reflecting, at least in part, varying FSH-R isoforms.
Robinson
Lisa J
LJ
Departments of Pathology and of Cell Biology and Physiology, University of Pittsburgh, and Veteran's Affairs Medical Center, Pittsburgh, PA 15243, USA.
Tourkova
Irina
I
Wang
Yujuan
Y
Sharrow
Allison C
AC
Landau
Michael S
MS
Yaroslavskiy
Beatrice B
BB
Sun
Li
L
Zaidi
Mone
M
Blair
Harry C
HC
D016723:Bone Remodeling / Q000187:drug effects / Q000235:genetics*; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism* / Q000494:pharmacology; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D011962:Receptors, FSH / Q000819:agonists / Q000378:metabolism*; D013739:Testosterone / Q000494:pharmacology; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D004967:Estrogens; D020033:Protein Isoforms; D011962:Receptors, FSH; D014409:Tumor Necrosis Factor-alpha; D013739:Testosterone; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP