G-proteins and hormonal signalling in human pituitary tumors: Genetic mutations and functional alterations

A. Spada, L. Vallar, G. Faglia

Research output: Contribution to journalArticlepeer-review

Abstract

In the last few years, molecular studies on pituitary adenomas have yielded several lines of evidence supporting a primary pituitary origin for these tumors. In fact, analyses of x-chromosomal inactivation show that the great majority of pituitary tumors are monoclonal in origin, suggesting that one or more mutations are responsible for the selective expansion of a single cell clone. Mutations constitutively activating GTP-binding proteins have been identified in subsets of pituitary adenomas. Single amino acid substitutions replacing Arg 201 with either Cys, His, or Gln 227 with either Arg or Leu of the α-subunit of the Gs gene were identified in one third of growth hormone (GH)-secreting adenomas. Both mutations stabilize αs in its active conformation by inhibiting GTPase activity, thus mimicking the effect of specific extracellular growth factors, such as growth hormone releasing hormone (GHRH). Since several lines of evidence suggest that cAMP is involved in somatotrope replication, it has been proposed that the αs gene can be converted into an oncogene, designated gsp (for Gs protein). Recently, the ras oncogene has been identified in one prolactinoma characterized by unusual invasiveness. Although these data seem to negate a primary role for hypothalamic neurohormones in adenoma formation, it is conceivable that the hormones may exert a role in the sequence of events leading to clonal expansion of a transformed cell. Moreover, alterations in receptor and/or postreceptor events triggered by hypothalamic neurohormones may result in amplification of stimulatory inputs and impairment of inhibitory ones.

Original languageEnglish
Pages (from-to)214-232
Number of pages19
JournalFrontiers in Neuroendocrinology
Volume14
Issue number3
DOIs
Publication statusPublished - 1993

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrine and Autonomic Systems

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