Macrophage colony stimulating-factor transcripts are differentially regulated in rat bone-marrow by gender hormones.
There are at least three forms of macrophage colony-stimulating factor (M-CSF), a cytokine that is critical for osteoclast formation; and evidence exists that the membrane-bound form is involved in this process. We wished to test the hypothesis that the expression of the membrane form of M-CSF is modulated by the presence of gender steroids. This was achieved by analyzing M-CSF messenger RNA and protein in the bone-marrow of estrogen- and androgen-replete, and -deficient female rats. We found that the 1.4-kb M-CSF transcript was not detected in sham-operated rats but that the 4.6-kb transcript was expressed in abundance. In contrast, these transcripts were differentially expressed in ovariectomized rats, and this effect was reversed by 17beta-estradiol treatment. Administration of androstenedione to ovariectomized rats, so that androstenedione plasma levels were restored to just below that in sham-operated rats, also suppressed the expression of the 1.4-kb M-CSF transcript. This effect was abrogated by antiandrogen treatment, indicating that this was an androgen-mediated effect. The membrane-bound protein was detected in the bone-marrow of sham-operated rats and was elevated post ovariectomy, whereas ovariectomy had no effect on the soluble isoform. Our data support the hypothesis that the membrane form of M-CSF is modulated by gender hormones and that this isoform is involved in the estrogen- and androgen-mediated effects on the skeleton.
Lea
C K
CK
Department of Histopathology, Imperial College School of Science, Technology and Medicine at St. Mary's, London, United Kingdom.
Sarma
U
U
Flanagan
A M
AM
D000077384:Anastrozole; D000726:Androgen Antagonists / Q000494:pharmacology; D000735:Androstenedione / Q000494:pharmacology / Q000502:physiology*; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000097:blood; D004967:Estrogens / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics*; D008970:Molecular Weight; D009570:Nitriles / Q000494:pharmacology; D010052:Ovariectomy; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D014105:Tosyl Compounds; D014158:Transcription, Genetic; D014230:Triazoles / Q000494:pharmacology
D000726:Androgen Antagonists; D000813:Anilides; D004791:Enzyme Inhibitors; D004967:Estrogens; D009570:Nitriles; D012333:RNA, Messenger; D014105:Tosyl Compounds; D014230:Triazoles; D000077384:Anastrozole; D000735:Androstenedione; D004958:Estradiol; D016173:Macrophage Colony-Stimulating Factor; C053541:bicalutamide