Role of regulatory factors in pituitary tumour formation.

Journal article

The molecular basis of pituitary tumorigenesis remains controversial, but there are two major theories which have been subject to most investigation: hormonal (usually hypothalamic factors) and/or growth factor overstimulation, or a molecular defect within the pituitary itself. It has been shown, for example, that excessive regulatory hormone stimulation can lead to an increased number of cells in the pituitary in various physiological or pathological states such as pregnancy (lactotrophs), untreated primary hypothyroidism (thyrotrophs and lactotrophs),primary hypoadrenalism (corticotrophs) and ectopic GHRH-secreting tumours (somatotrophs). Animal models also provide data that in the presence of excessive hypothalamic hormone stimulation, adenoma formation can occur. However, evidence in favour of the monoclonal nature of pituitary tumours argues for an intrinsic molecular defect as the primary initiating event in tumour formation. We review the various hormonal factors and their receptors effecting the different types of pituitary cells, such as CRH, AVP and cortisol feedback on corticotrophs; GHRH, Galpha PKA, somatostatin and GH and IGF feedback on somatotrophs; GnRH, LH/FSH, activin and oestrogen feedback on gonadotrophs; dopamine, oestrogen and prolactin feedback on lactotrophs; and TRH, TSH and thyroid hormone feedback on thyrotrophs. The monoclonal origin of adenomas makes it unlikely that hypothalamic factors could initiate pituitary transformation, but they could still create an environment where there is a higher chance that a possible causative tumorigenic mutation may occur in one (or several) of the overstimulated pituitary cells, or enhance the proliferation of an already-mutated cell.

Authors: Korbonits, M; Morris, D; Nanzer, A; Kola, B; Grossman, AB

• Publication status: Published
• Journal: Frontiers of hormone research
• Volume: 32
• Pages: 63-95
• Publication date: 2004-01-01
• DOI: 10.1159/000079038
• EISSN: 1662-3762
• ISSN: 0301-3073
• Language: English
• Keywords: Animals; Receptors, Cell Surface; Adenoma; Humans; Pituitary Gland; Hormones; Pituitary Neoplasms