title: Effects of nitric oxide synthase inhibition on diethylstilbestrol-induced hyperprolactinaemia and pituitary tumourigenesis in rats.
abstract: BACKGROUND
  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 rats.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These findings indicate that NO is involved in oestrogen-induced hyperprolactinaemia, but does not play a crucial role in oestrogen-induced pituitary tumourigenesis.
authors.affiliation: 1st Chair of Endocrinology, Department of Immunoendocrinology, Medical University of Łódź, ul. Sterlinga 3, 91-425 Łódź, Poland. marek.pawlikowski@umed.lodz.pl
authors.forename: Marek
authors.initials: M
authors.lastname: Pawlikowski
authors.forename: Hanna
authors.initials: H
authors.lastname: Pisarek
authors.forename: Jolanta
authors.initials: J
authors.lastname: Fryczak
authors.forename: Henryk
authors.initials: H
authors.lastname: Stępień
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D006966:Hyperprolactinemia / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000139:chemically induced* / Q000378:metabolism; D011388:Prolactin / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D004968:Estrogens, Non-Steroidal; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D004054:Diethylstilbestrol; D011388:Prolactin; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester