Stimulated growth of submandibular gland.

The effects of chronic isoproterenol (IPR) administration on the growth of submandibular gland were studied. Treatment of female rats with IPR, 0.02 mg. per gm. of body weight, twice daily between 13 and 29 days of age resulted in a 3.6-fold increase in the weight of the submandibular gland, with a 4-fold increase in ribonucleic acid and 1.8-fold increase in deoxyribonucleic acid content. Incorporation of tritiated thymidine was stimulated by two injections of the drug but it was below the control level after 5 days of IPR administration. When the administration of IPR was discontinued, the weight of the gland rapidly declined and within 11 days it reached the control level. However, the average deoxyribo-nucleic acid content of the glands of IPR-treated rats remained 20 to 25% above the control level. IPR treatment altered the cellular composition of the gland and influenced the proliferation of the various cell types differently. Between 14 and 30 days of age, the frequency of acinar cells increased from 29% to 44%. Concomitantly, the frequency of terminal tubule cells declined from 30% to 15%. There were no significant changes in the relative frequencies of other cell types during this developmental period. Chronic administration of IPR led to an increase in the frequency of acinar cells. At the same time the relative proportion of terminal tubule cells declined. During the observation period, the proliferative activities (labeling indices) of all cell types, except that of the ductal cells, declined. IPR treatment ahd the most pronounced, depressing effect on the proliferation of the acinar cells. At the same time, the drug accelerated the differentiation of acinar cells and it caused their marked hypertrophy. Administration of IPR to growing rats affords a favorable system for analysis of the relationship between normal and drug-induced growth.