METABOLISM OF ANDROGENS BY THE MOUSE SUBMANDIBULAR-GLAND AND EFFECTS OF THEIR METABOLITES

In the mouse submandibular gland, sexual difference becomes evident on day 30, when the granular convoluted tubules (GCT) of the gland rapidly grow in response to drastically increased levels of circulating testosterone and 5alpha-dihydrotestosterone (DHT) in the male. We studied the in vitro metabolism of both androgens by the mouse gland and the effects of their metabolites on the gland. By the glands on days 20 and 30, H-3-testosterone was not further converted to any derivatives. In contrast, H-3-DHT used as a substrate was metabolized partly to H-3-5alpha-androstane-3alpha,17beta-diol (3alpha-diol) and H-3-5alpha-androstane-3beta,17beta-diol (3beta-diol) in both sexes (approximately 9 and 1%, respectively). On the basis of the metabolites identified, the gland contained both 3alpha- and 3beta-hydroxysteroid dehydrogenase activities, which were not sexually different. Neonatally-castrated mice were given daily injections of 3alpha-diol, 3beta-diol, testosterone and DHT for 1-10 days from day 20. The relative occupied area (ROA) of GCT in the gland increased in both sexes by treatment with 3alpha-diol or DHT for 4 days, or by 3beta-diol or testosterone for 10 days. The order of ROA gain after 4-10 days was DHT > 3alpha-diol > testosterone > 3beta-diol. The mitotic activity of GCT increased in both sexes by treatment with 3alpha-diol or DHT for 4 days, but in only males by 3beta-diol or testosterone for 10 days. The results suggest that in the mouse gland testosterone exerts its effects without any intraglandular conversion, and that DHT primarily acts in its form, whereas its intraglandular metabolite, 3alpha-diol may be supplementary as a stimulant.