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The IGF axis in the prostate

P Cohen¹, D M Peehl, R G Rosenfeld

¹Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia.

Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Metabolisme

|February 1, 1994

Summary

The human prostate contains a functional insulin-like growth factor (IGF) system, with prostate cells producing IGFs and binding proteins. Prostate specific antigen (PSA) acts as an IGFBP-3 protease, influencing IGF action.

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Area of Science:

Endocrinology
Molecular Biology
Urology

Background:

The insulin-like growth factor (IGF) axis regulates cell growth and is implicated in various physiological processes.
Human seminal plasma contains components of the IGF axis, suggesting a potential prostatic origin.
The prostate's role in the IGF system is not fully understood.

Purpose of the Study:

To investigate the presence and function of the IGF axis within the human prostate.
To determine if prostate cells produce IGFs, IGF binding proteins (IGFBPs), and associated proteases.
To explore the role of prostate specific antigen (PSA) in modulating IGF action.

Main Methods:

Primary culture of human prostate fibroblasts (PC-F) and epithelial cells (PC-E).
Analysis of mRNA and peptide production for IGFs, IGFBPs, and IGFBP proteases.
Assessment of IGF receptor expression in prostate cells.
Functional assay of PSA as an IGFBP-3 protease.

Main Results:

Prostate fibroblasts (PC-F) express IGF-II mRNA and produce bioactive IGF-II.
Prostate epithelial cells (PC-E) express the type I IGF receptor and produce IGFBP-2 and IGFBP-4.
PC-F secrete IGFBP-2, IGFBP-3, and IGFBP-4.
PC-E are highly sensitive to IGF mitogenic effects.
PSA exhibits potent IGFBP-3 protease activity, potentially releasing IGFs from inhibitory binding proteins.

Conclusions:

The human prostate possesses all components of a functional IGF system.
Prostate cells actively produce and secrete IGFs, IGFBPs, and IGFBP proteases.
PSA's IGFBP-3 protease activity suggests a mechanism for regulating IGF action within the prostate and seminal fluid.

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