Path. Res. Pract. 187,581-583 (1991) The Role of 'Hypothalamic Hormones in the Pathogenesis of Pituitary Adenomas Introduction S. L. Asa Department of Pathology, Sf. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada SUMMARY There is evidence that hypothalamic hormones can regulate hormone secretion by pituitary adenomas. Hormone release by adenomas can be stimulated by hypothalamic releasing peptides; several hypothalamic inhibitory hormones or their analogues are used in the therapy of pituitary tumors to suppress hormone secretion and, in some cases, to reduce tumor size. A role for hypothalamic hormones in the development and growth of pituitary tumors has also been suggested by the association of pituitary adenomas with tumors producing hypothalamic hormones. In particular, tumors producing growth hormone- releasing hormone (GRH) or corticotropin-releasing hormone (CRH) have been asso- ciated with hyperplasia of their target adenohypophysial cells; a few have had pituitary neoplasms. Investigations have shown that some adenohypophysial cells respond to sustained stimulation by hypothalamic pep tides with cell proliferation, however, it was not proven that the sustained stimulation resulted in the development of tumors. Recently, an animal model of disease was provided by mice transgenic for G RH. At 8 months of age, the mice developed pituitary mammosomatotroph hyperplasia; mice older than 12 months developed pituitary mammosomatotroph adenoma. It is suggested that continued hormonal stimulation plays a role in tumorigenesis, probably by promotion of cell replication. Hypothalamic hormones are known to regulate hor- mone release by adenohypophysial cells and their tumors. The presence of receptors for hypothalamic stimulating hormones led some investigators to suggest that hypotha- lamic stimulation plays a role in the development of pituitary tumors 18 • Others have implicated lack of sup- pression by hypothalamic inhibitory hormones in tumor formation 9 . hormone (GRH) and corticotropin (ACTH)-releasing hor- mone (CRH) that may playa role in the pathogenesis of pituitary adenomas. Material and Methods Planned experiments of man have localized receptors for hypothalamic hormones on pituitary tumor cells and sought proof of responsiveness to hypothalamic stimulation in vivo and in vitro. Clinical trials have administered synthetic hypothalamic peptides and monitored their effects by measurement of the hormones produced by target cells of these substances. The proliferative response to sustained stimulation by hypothalamic releasing hormones has been assessed by measuring the incorpo- ration of tritiated thymidine into cultured adenohypophysial cells. The evidence that hypothalamic hormones can playa role in the development of pituitary tumors as well as their function has accumulated from three sources: 1) planned experiments of man, 2) unplanned experiments of nature and 3) animal models of disease. This paper will focus on the stimulatory effects of growth hormone (GH)-releasing © 1991 by Gustav Fischer Verlag, Stuttgart 0344-0338/91/0187-0581$3.50/0