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Inhibins, activins, and follistatins: expression of mRNAs and cellular localization in tissues from men with benign
T Z Thomas1, S M Chapman, W Hong
1Institute of Reproduction and Development, Monash Medical Center, Clayton, Victoria, Australia.
Background:
The transforming growth factor beta (TGF beta) superfamily of growth factors includes activins and inhibins, which have been shown to be present in the rat ventral prostate, and human prostate tumor cell lines, although their localization in benign prostatic hyperplasia (BPH) tissue is currently unknown.
Methods:
BPH tissues were obtained at surgery, and the mRNA expression for the inhibin alpha, beta A, beta B subunits, the putative activin beta C subunit, the activin type II receptor (ActRII), and the activin binding protein, follistatin, was determined by reverse transcription polymerase chain reaction (RT-PCR) and Southern blot analysis. Antibodies specific for alpha, beta A, beta B, activin A, and follistatin were used to determine the localization of these proteins in BPH tissue specimens.
Results:
Southern blot analysis confirmed that mRNA for ActRII, beta C subunit, and follistatin was present in all biopsy samples assayed. However, alpha, beta A, and beta B subunit mRNA expression was variable between patient samples. Immunohistochemistry demonstrated the predominant localization of beta A, beta B, and activin A proteins to the epithelium of BPH tissues. No immunoreactivity for the inhibin alpha subunit was detected; follistatin immunoreactivity was localized to the fibroblastic stroma.
Conclusions:
The compartmentalization of activin subunit proteins to the epithelium, and of follistatin to the stroma, suggests that a paracrine interaction occurs between the activin ligands and follistatin-binding proteins in BPH tissue.
Insights
Activin and follistatin proteins are localized in different compartments within benign prostatic hyperplasia (BPH) tissue, suggesting paracrine interactions. This finding offers new insights into BPH pathogenesis and potential therapeutic targets.
Area of Science:
- Endocrinology
- Urology
- Cell Biology
Background:
- The transforming growth factor beta (TGF-β) superfamily includes activins and inhibins, found in prostate tissues.
- Their specific localization in benign prostatic hyperplasia (BPH) tissue was previously unknown.
Purpose of the Study:
- To investigate the presence and localization of activin and inhibin subunits, their receptor, and follistatin in BPH tissue.
- To elucidate potential paracrine interactions within BPH.
Main Methods:
- Reverse transcription polymerase chain reaction (RT-PCR) and Southern blot analysis to detect mRNA expression.
- Immunohistochemistry using specific antibodies to determine protein localization.
Main Results:
- mRNA for activin type II receptor (ActRII), beta C subunit, and follistatin was consistently detected.
- Expression of alpha, beta A, and beta B subunit mRNA varied among patients.
- Activin A, beta A, and beta B proteins localized to the BPH epithelium, while follistatin localized to the stroma. No inhibin alpha subunit protein was detected.
Conclusions:
- Activin subunit proteins are compartmentalized to the epithelium.
- Follistatin is localized to the stroma.
- This compartmentalization suggests paracrine interactions between activin ligands and follistatin-binding proteins in BPH tissue.