Ovarian androgens protect against bone loss in rats made oestrogen deficient by treatment with ICI 182,780.
We tested the hypothesis that ovarian androgens play a role in protecting against cancellous bone loss in oestrogen-deficient states and that conversion of androgens to oestrogens is not catalysed by aromatase P450 in the bone or bone-marrow microenvironment. We did this by administering the anti-oestrogen, ICI 182,780, alone and in combination with the anti-androgen, Casodex, and compared the effects on the skeleton with those of ovariectomy. We found that rats subjected to ovariectomy lost significantly greater cancellous bone volume compared with those treated with ICI 182,780, but that combination anti-oestrogen and anti-androgen therapy resulted in bone loss equivalent to that in ovariectomised animals. The skeletal-protective effect of preserving the ovaries in animals which had been chemically ovariectomised was attributed to suppression of osteoclast parameters. Taken together, these data suggest that a reduction in ovarian androgens accentuates the increase in osteoclast number and the reduction in cancellous bone volume which occurs in oestrogen-deficient states. Failure to detect transcripts for aromatase cytochrome P450 in the bone and bone-marrow of rats provides supportive evidence that androgens mediate their skeletal-protective effect directly and not by peripheral conversion to oestradiol.
Lea
C K
CK
Department of Histopathology, Imperial College of Science, Technology and Medicine at St Mary's, Norfolk Place, London, UK.
Flanagan
A M
AM
D000704:Analysis of Variance; D000726:Androgen Antagonists / Q000494:pharmacology; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D000077267:Fulvestrant; D015850:Interleukin-6 / Q000235:genetics; D009570:Nitriles; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014105:Tosyl Compounds; D014599:Uterus / Q000033:anatomy & histology
D000726:Androgen Antagonists; D000813:Anilides; D004965:Estrogen Antagonists; D015850:Interleukin-6; D009570:Nitriles; D012333:RNA, Messenger; D014105:Tosyl Compounds; D000077267:Fulvestrant; D004958:Estradiol; C053541:bicalutamide; D001141:Aromatase