Glucocorticoid-like actions of medroxyprogesterone acetate upon MtTW15 rat mammosomatotropic pituitary tumors.
We have shown recently that the MtTW15 experimental rat pituitary tumor responds to medroxyprogesterone acetate (MPA) by increasing GH production. In this study, using a single saturating dose assay and dextran-coated charcoal separation, the data indicate that the MtTW15 tumor contains cytosolic MPA binding sites. The concentration of sites (approximately 4 pmol/g tumor) was similar for tumors derived from male or female hosts but was significantly reduced in tumors from MPA- or estradiol-treated rats. The MPA binder sedimented to 4S on low salt sucrose density gradients and was of high affinity (Kd = 5.0 +/- 0.4 X 10(-9) M). However, binding specificity studies showed glucocorticoids to be better ligands than MPA. MtTw15 tumors were also analyzed for cytosolic progestin ([3H]R5020) and glucocorticoid ([3H]dexamethasone) binding sites. Only low levels of an estradiol-inducible progestin binder were found. In contrast, the concentration of glucocorticoid binding sites was similar to that observed for MPA, approximately 4 pmol/g tumor, as were the characteristics of the binding, i.e. 5.1 +/- 0.2S, Kd = 4.1 +/- 0.5 X 10(-9) M, and similar binding specificities. Both MPA and estradiol treatment of tumor-bearing rats decreased the concentration of both MPA and glucocorticoid binding sites. Furthermore, studies to determine if glucocorticoids would mimic the in vivo effect of MPA upon MtTW15 tumors, i.e. altered tumor hormone production, supported such a hypothesis. We conclude that the MtTW15 rat pituitary tumor contains a cytosolic glucocorticoid receptor and that MPA can interact with this receptor. The glucocorticoid receptor may be responsible for the MPA- and glucocorticoid-induced alterations in GH production.
D000818:Animals; D001667:Binding, Competitive; D003600:Cytosol / Q000378:metabolism; D003907:Dexamethasone / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids; D013006:Growth Hormone / Q000096:biosynthesis*; D007700:Kinetics; D008297:Male; D008525:Medroxyprogesterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D017258:Medroxyprogesterone Acetate; D009374:Neoplasms, Experimental / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011388:Prolactin / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D011965:Receptors, Glucocorticoid / Q000378:metabolism
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D004958:Estradiol; D003907:Dexamethasone; D011388:Prolactin; D013006:Growth Hormone; D017258:Medroxyprogesterone Acetate; D008525:Medroxyprogesterone