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Macrophage Colony Stimulating-Factor Transcripts Are Differentially Regulated in Rat Bone-Marrow by Gender Hormones¹

Department of Histopathology, Imperial College School of Science, Technology and Medicine at St. Mary’s, London W2 1PG, United Kingdom

Address all correspondence and requests for reprints to: Adrienne M. Flanagan, Department of Histopathology, Imperial College School of Science, Technology and Medicine at St. Mary’s, Norfolk Place, London W2 1PG, United Kingdom. E-mail: a.flanagan{at}ic.ac.uk

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 17ß-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.

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