THE ROLE OF HYPOTHALAMIC HORMONES IN THE PATHOGENESIS OF PITUITARY-ADENOMAS

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 associated 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 peptides 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 GRH. 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.