Many hormones bind Gsα-coupled receptors in order to activate their endocrine glands for proliferation, differentiation, and hormone secretion. Accordingly, mutations that cause constitutive Gsα activity are found in various functionally active endocrine adenomas, including those that originate from pituitary somatotrophs. In about 40% of patients with growth hormone secreting pituitary adenomas, constitutively activating Gsα missense mutations at either Arg201 or Gln227 have been identified in DNA from the tumor tissue, but not in DNA from peripheral blood [20, 97]. Since these mutant Gsα forms are identified in tumors and are present in one of the Gsα alleles only, they are referred to as the gsp oncogene [20, 97]. Other endocrine tumors also bare the gsp oncogene, including corticotroph, thyroid, parathyroid, and adrenocortical tumors, but their frequency in the patient population appears to be low based on many studies (reviewed in [98]). Some studies have recently identified the gsp oncogene in ovarian granulosa cell tumors and testicular stromal Leydig cell tumors as a possible cause of tumorigenesis and as a possible prognostic marker [99, 100]. In a more recent study, 5
