The effect of progestins on submaxillary gland epidermal growth factor: demonstration of androgenic, synandrogenic and antiandrogenic actions.

The effects of progestins (0.1, 1.0, 6-10 mg/day) alone and in combination with testosterone (0.1 mg/day) on immunoreactive epidermal growth factor (EGF) concentrations in submaxillary glands from normal and androgen-insensitive (tfm/y) mice were studied. Since androgens are known to stimulate increased EGF levels, the responses to progestins were interpreted as androgenic, synandrogenic or antiandrogenic if they simulated, potentiated or inhibited androgen response, respectively. Of the progestins studied, medroxyprogesterone acetate (MPA) caused the greatest androgenic response when given alone; 10 mg produced a greater than 40-fold increase of EGF over control values. Lesser responses were achieved when progesterone or megestrol acetate (Meg Ac) were given alone. Cyproterone acetate (Cyp Ac) had no androgenic activity when administered alone and acted as a potent antiandrogen at all doses used. Progesterone and Meg Ac had weak antiandrogenic activity. The only synandrogenic response elicited was with a high dose (10 mg) of progesterone caproate. Neither MPA nor progesterone alone had any effect on EGF levels in tfm/y mice. These patterns of response differ from those seen in mouse kidney. The data indicate that progestins as a class are capable of androgenic, synandrogenic and antiandrogenic action in the mouse submaxillary gland, but that no single progestin is capable of all three actions. Since tfm/y mice lack a functional androgen receptor, the absence of EGF response in these mice to progestins as well as androgens suggest that the action of progestins may be mediated by the androgen receptor in the submaxillary gland.