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The pathogenesis of pituitary tumours

Nature Reviews Cancer volume 2, pages 836–849 (2002)Cite this article

Key Points

Summary

  • The pituitary gland is required for the maintenance of normal homeostasis of the individual, and is essential for propagation of the species.

  • Pituitary tumours can be the cause of mood disorders, sexual dysfunction, infertility, obesity and disfigurement, visual disturbances, hypertension, diabetes mellitus and accelerated heart disease.

  • Pituitary tumours are found in 20% of the population, but only one-third of these give rise to clinical manifestations.

  • Hormones that modulate normal pituitary hormonal activity and growth factors that are implicated in normal fetal pituitary development have been implicated in pituitary tumour growth, but are not likely to be the cause of human pituitary tumours.

  • Discrepancies between mouse models and human pituitary tumours might reflect different mechanisms of tumorigenesis, species variations or distinct methodologies.

  • Genetic mutations that are characterized in other human neoplasms are rare in human pituitary tumours.

  • Only a small percentage of pituitary tumours are associated with the inherited disorder, multiple endocrine neoplasia type 1 syndrome.

Abstract

Pituitary tumours are common and show a range of hormonal and proliferative behaviours that provide a model for the study of neoplasia mechanisms. Mutations in classic oncogenes and tumour-suppressor genes, however, are rarely associated with these tumours. In fact, most mechanisms of endocrine tumorigenesis differ significantly from those associated with haematological malignancies and non-endocrine tumours. Instead, tumorigenesis is promoted by hormones and growth factors that are implicated in pituitary development. Several mouse models have validated the roles of these alterations, although there are many differences in disease pathogenesis between mice and humans.

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Figure 1: Pituitary anatomy and cell types.
Figure 2: Regulatory pathways in pituitary somatotrophs.
Figure 3: Regulatory pathways in pituitary lactotrophs.
Figure 4: Regulatory pathways in pituitary gonadotrophs.
Figure 5: Regulatory pathways in pituitary corticotrophs.
Figure 6: Proposed model of pituitary tumorigenesis.

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Acknowledgements

This work was supported in part by grants from the Canadian Institutes of Health Research and the Toronto Medical Laboratories.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Department of Pathology, University of Toronto, University Health Network and Toronto Medical Laboratories (SLA), 610 University Avenue, Toronto, M5G 2M5, Ontario, Canada

    Sylvia L. Asa & Shereen Ezzat

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Correspondence to Sylvia L. Asa.

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DATABASES

Cancer.gov

pituitary tumours

GenBank

SV40 T antigen

LocusLink

ACTH

activins

ActRII

ALK4

CDC2

CDK2

CDK4

Cdkn2c

cortactin

CREB

CRH

cyclin D

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D2R

EGF

EGFR

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ERBB3

ERBB4

FAST

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FGF8

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GAP43

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GFG

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HRAS

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KIP1

KIP2

KRAS

MAPK

MDM2

MEN1

N-CAM

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NGF

NRAS

p14

p19

p53

PIT1

PKA

PKC

PRKAR1

prolactin

Pttg

PTTG

Rb

RB

SMAD3

somatostatin

c-SRC

Sstr2

SSTR2

TGF-α

TGF-β

TRH

TSH

vasopressin

Vegf

VEGF

WAF1

OMIM

acromegaly

Carney's complex

Cushing's disease

McCune?Albright syndrome

MEN1 syndrome

FURTHER INFORMATION

Endocrine Society

Hormone Foundation

Pituitary Society

PNA

Glossary

SELLA TURCICA

The bony box that saddles the pituitary gland.

PROLACTINOMAS

Tumours of pituitary lactotrophs that produce prolactin.

MONOALLELIC IMPRINTING

Gene expression from a single allele, which is often associated with methylation of the promoter on the inactive allele.

SUPRASELLAR EXTENSION

Growing outside of the sella turcia upwards.

LOSS OF HETEROZYGOSITY (LOH)

Loss of one or more alleles on one member of a chromosome pair during tumorigenesis.

CYTODIFFERENTIATION

The process that is involved in specialized cell differentiation and maintenance of cell lineage.

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Asa, S., Ezzat, S. The pathogenesis of pituitary tumours. Nat Rev Cancer 2, 836–849 (2002). https://doi.org/10.1038/nrc926

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