Spontaneous Sparsely-Granulated Prolactin-Producing Pituitary Adenomas in Aging Rats

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Abstract
The effect of bromocriptine (BEC) treatment on spontaneous, sparsely granulated, prolactin-producing pituitary adenomas was studied in aging female Long-Evans rats of at least 23 months of age. Rats treated with BEC for 1–44 days showed a marked decrease in serum prolactin (PRL) concentrations at the end of the treatment period (9.1–34 ng/ml) when compared to the serum PRL levels of age-matched control animals (94.6–233 ng/ml). No significant differences in serum PRL levels (ng/ml; mean ± SEM) were noted in rats withdrawn for 14 days from BEC treatment (132.9 ± 18.8) when compared to age-matched controls (181.5 ± 70.9). The mean pituitary weight (mg) was significantly reduced in the rats treated for 44 days with BEC (23.4 ± 1.4) compared to untreated controls (43.4 ± 8.3). At the time of sacrifice, PRL-producing adenomas were found in 16 of 33 control rats, 5 of 10 rats treated for 1 day with BEC, 5 of 20 rats treated with BEC for 44 days, and 12 of 28 rats in the animals withdrawn from BEC treatment for 14 days. Morphometric analysis of sparsely granulated PRL-containing adenomas revealed that, althought the nuclear area was reduced after 1 day of BEC treatment, the cytoplasmic area was reduced only after 44 days. Forming granule diameters were significantly increased after 44 days of BEC treatment and markedly decreased in the withdrawal group. Storage granule diameters were increased in both the 1-day and 44-day groups and were decreased in rats withdrawn from BEC for 14 days. Rough endoplasmic reticulum, forming granule, storage granule, and lysosome volume densities were increased after 1 day of BEC treatment. The Golgi region volume density decreased only after 44 days of BEC treatment. We conclude that aging female Long-Evans rats harboring PRL-producing pituitary adenomas can respond to BEC administration with a decrease in serum PRL levels and morphologic changes in adenoma cells. However, the structural alterations in PRL cells of the rat adenomas are less conspicuous than those of human tumors. In the rat, like in human patients, a direct toxic effect of BEC on PRL-producing adenoma cells has not been demonstrated.