The usefulness of somatotroph-specific aryl hydrocarbon receptor interacting protein knock out (sAIPKO) mice in developing therapeutics for GH secreting pituitary adenoma

Abstract

Acromegaly results from the chronic hypersecretion of GH, which primarily originates from GH secreting pituitary adenoma. Although transsphenoidaladenomectomy is the treatment of choice, some patients do not achieve biochemical remission after surgery and require medical treatment. However, there are not many available drugs due to the limitations of GH-secreting pituitary adenoma which include the poorly understood pathogenesis and lack of a proper animal model. Recently, Igenerated an animal model that develops GH secreting pituitary adenoma, which has the deletion of the aryl hydrocarbon receptor interacting protein (AIP) in somatotroph. To investigate the usefulness of somatotroph-specific AIP knock out (sAIPKO) mice in developing therapeutics for GH secreting pituitary adenoma, I evaluated the biochemical effects of somatostatin analogs on sAIPKO mice. I generated sAIPKO mice using a Cre-loxp strategy. Twelvemale sAIPKO mice were assessed. The mice received a subcutaneous injection of octreotide LARor pasireotide LAR. Imeasured serum IGF-1 levels, body weight and blood glucose levels three times a month. There were significant decreases in serum IGF-1 levels in the pasireotide group. However, serum IGF-1 levels inthe octreotide group showed a decreasing trend, although it was not statistically significant. Body weight in the pasireotide group significantly decreased on the 14th day, not on the 28th day while there was no significant change in the octreotide group. Blood glucose levels in the pasireotide group increased significantly on 28th day.Pasireotide which is a multireceptor targeted somatostatin analog, had stronger inhibitory effects on biochemical activity in sAIPKO mice suggesting that this mouse model represent more aggressive GH secreting pituitary adenoma. Thus, this mouse model will be useful for drug development and efficacy evaluation in GH secreting pituitary adenoma.