Progestin regulation of galanin and prolactin gene expression in oestrogen-induced pituitary tumours

Galanin is a peptide widely distributed in the hypothalamic-pituitary axis. In the female rat pituitary, galanin is mainly present in lactotrophs, whe re it regulates their secretion and proliferation. Galanin expression is in creased in oestrogen-induced prolactinomas, and it has been proposed that o estrogen effects on lactotroph function and proliferation could be mediated by galanin. Previous studies from our laboratory demonstrated that the syn thetic progestin levonorgestrel antagonizes pituitary tumorigenesis of rats given oestrogen, reducing the number of proliferating cells and increasing cell death by nonapoptotic mechanism(s). To elucidate the role of galanin in levonorgestrel effects on the tumours, we examined galanin and prolactin mRNA and peptide expression in prolactinomas of rats receiving the progest in. Levonorgestrel reduced the pituitary weight and serum prolactin concent rations in oestrogen-treated rats. Galanin mRNA expression (determined by i n situ hybridization), and the number of galanin expressing cells (determin ed by immunocytochemistry) were also reduced by the progestin in tumour-bea ring rats. However. neither prolactin mRNA content, nor the number of prola ctin-expressing cells, were modified by levonorgestrel treatment of oestrog en-receiving rats. The present study suggests that levonorgestrel controls pituitary growth by diminishing galanin expression. In contrast, changes in serum prolactin concentration seem to be more related to the reduction in tumour size, since the reduction in galanin expression was not large enough to regulate prolactin mRNA expression or the percentage of lactotrophs.