Adrenocortical tumorigenesis, luteinizing hormone receptor and transcription factors GATA-4 and GATA-6

Susanna Vuorenoja, Adolfo Rivero-Muller, Sanne Kiiveri, Malgorzata Bielinska, Markku Heikinheimo, David B. Wilson, Ilpo T. Huhtaniemi, Nafis A. Rahman

Research output: Contribution to journalReview article

35 Scopus citations

Abstract

Luteinizing hormone (LH/hCG) responsiveness of normal and pathological human adrenal glands as well as the possibility of constitutive expressions of luteinizing hormone receptor (LHR) in adrenal cortex has been reported. Some recent studies showed a correlation between the LHR and abundant GATA-4 expression in both metastasizing and non-metastasizing human adrenocortical tumors, but not in normal adrenals, implicating the putative relevance of LHR and GATA-4 for adrenocortical pathophysiology. However, the physio- and pathophysiological significance of LHR and GATA-4 in the mechanism of adrenocortical tumorigenesis remains unclear. The paucity of suitable models for adrenal tumorigenesis makes the establishment of proper animal models highly important. LHR expression in the murine adrenal gland is an exception and not found in wild-type (WT) animal. We have previously shown that ectopic LHR expression in the murine adrenal gland can be induced by chronically elevated LH levels. We have generated a gonadotropin-responsive adrenal tumor model in gonadectomized transgenic (TG) mice expressing the inhibin α promoter/Simian Virus 40 T antigen transgene (inhα/Tag). Given the induction of expression and regulation of GATA-4 and GATA-6 zinc finger transcription factors in the gonads by gonadotropins, this review will explore their relationship to LHR expression and their role in adrenocortical tumorigenesis. A functional link between LHR and GATA-4 actions in the adrenal pathophysiology is proposed.

Original languageEnglish
Pages (from-to)38-45
Number of pages8
JournalMolecular and Cellular Endocrinology
Volume269
Issue number1-2 SPEC. ISS.
DOIs
StatePublished - Apr 15 2007

Keywords

  • Adrenal tumors
  • Gonadotropins
  • LHR
  • Transcription factors GATA-4 and GATA-6
  • Transgenic mice

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    Vuorenoja, S., Rivero-Muller, A., Kiiveri, S., Bielinska, M., Heikinheimo, M., Wilson, D. B., Huhtaniemi, I. T., & Rahman, N. A. (2007). Adrenocortical tumorigenesis, luteinizing hormone receptor and transcription factors GATA-4 and GATA-6. Molecular and Cellular Endocrinology, 269(1-2 SPEC. ISS.), 38-45. https://doi.org/10.1016/j.mce.2006.11.013