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Pituitary Somatotroph Adenoma Producing Growth Hormone (GH)-Releasing Hormone (GHRH) with an Elevated Plasma GHRH Concentration: A Model Case for Autocrine and Paracrine Regulation of GH Secretion by GHRH¹

Department of Neurosurgery, Teikyo University Ichihara Hospital (A.M., T.N.), 3426–3 Anegasaki, Ichihara City, Chiba 299-0111; the Third Department of Internal Medicine, Miyazaki Medical College (H.K., S.M.), 5200 Kihara, Kiyotake Town, Miyazaki-gun, Miyazaki 889-1601; the Department of Pathology, Tokai University School of Medicine (N.Sa., R.Y.O.), Boseidai, Isehara City, Kanagawa 259-1100; and the Third Department of Internal Medicine, Teikyo University Ichihara Hospital (Y.O., N.Sh.), 3426–3 Anegasaki, Ichihara City, Chiba 299-0111, Japan

Address all correspondence and requests for reprints to: Akira Matsuno, M.D., D.M.Sc., Department of Neurosurgery, Teikyo University Ichihara Hospital, 3426–3 Anegasaki, Ichihara City, Chiba 299-0111, Japan.

An acromegalic patient with a pituitary somatotroph adenoma associated with an extremely elevated plasma GHRH concentration is presented. The preoperatively high concentration of plasma GHRH returned to the normal level after successful removal of the adenoma. GHRH production and GHRH gene expression were confirmed in the adenoma by studies including immunohistochemistry and in situ hybridization. Expression of GHRH receptor messenger ribonucleic acid was verified by in situ hybridization. Immunohistochemical double staining for GH and GHRH revealed their colocalization in single adenoma cells. These findings confirmed the autocrine or paracrine regulation of GH production by endogenous GHRH from the adenoma cells. GHRH synthesis in the pituitary gland has recently been demonstrated, however, there have been no previous reports of a GHRH-producing pituitary somatotroph adenoma associated with an elevated plasma GHRH concentration. The existence of this GHRH-producing adenoma suggests a possible role of locally generated GHRH in the progression of somatotroph adenomas, i.e. the monoclonally established somatotroph adenomas develop further under the influence of locally produced GHRH. The demonstration of GHRH production by this somatotroph adenoma is of importance in clarifying the autocrine or paracrine regulation of GH production and the progression of human somatotroph adenomas.

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