Binding of glucocorticoid to the androgen receptor of mouse submandibular glands

An increase in esteroprotease activity, a known cytodifferentiating response to androgen in the submandibular gland, occurred after cortisol acetate, dexamethasone or methyltrienolone (R1881) treatment in castrated genetically normal male (X/Y-castrated) mice, but not in normal male (X/Y) and testicular feminized male (Tfm/Y) mice. A peak with specific binding for [3H]cortisol appeared in sucrose density gradient patterns of extracts from X/Y-castrated mice and in almost the same fraction number as that for [3H]R1881 binding. However, peaks specific for neither [3H]cortisol nor [3H]R1881 binding were observed in Tfm/Y mice. The peak binding [3H]cortisol in extracts from X/Y-castrated mice, as well as the one binding [3H]R1881, were inhibited by unlabelled R1881 and cyproterone acetate, an antiandrogen; the peak was not, however, affected by unlabelled oestradiol-17 beta. The binding capacity of [3H]cortisol determined by Scatchard analysis was similar to that of [3H]R1881 (103 and 106 fmol/mg protein respectively). The Kd value of [3H]cortisol, however, was about 13.6-fold higher than that of R1881. These results suggest that cortisol has the ability to promote androgenic cytodifferentiating action in the mouse submandibular gland by binding to its androgen receptors, if androgens are absent or deficient.