Effects of nitric oxide synthase inhibition on diethylstilbestrol-induced hyperprolactinaemia and pituitary tumourigenesis in rats
The overexpression of nitric oxide synthase (NOS) has been found in tumours, including pituitary adenomas. It has also been found that NOS is overexpressed in human spontaneous pituitary adenomas. The question arises whether NOS and its product, nitric oxide (NO), are involved in pituitary tumourigenesis. To investigate this question, in the present paper we examine the effects of NOS inhibition on the development of diethylstilbestrol (DES)-induced prolactin-secreting pituitary tumours in
... ary tumours in rats. Thirty male Fisher 344 rats, four weeks old, were submitted to subcutaneous implantation of a silastic capsule containing DES (10 mg/capsule) or of an empty capsule. Six weeks after implantation, some of the DES-treated animals received a NOS inhibitor, N-nitro-l-arginine methyl ester (NAME), 1 mg/mL, in their drinking water, for the subsequent 14 days. Eight weeks after the implantation, all the animals were sacrificed, their pituitaries were weighed, and samples of heart blood were collected for prolactin (PRL) and vascular endothelial growth factor (VEGF) measurements. It was found that DES implantation significantly increased pituitary mass, as well as PRL and VEGF concentrations in blood serum. On the other hand, the administration of NAME did not affect significantly either VEGF concentration or pituitary mass. On the other hand, it did induce a further increase in PRL levels. These findings indicate that NO is involved in oestrogen-induced hyperprolactinaemia, but does not play a crucial role in oestrogen-induced pituitary tumourigenesis.