Regulation of prostate branching morphogenesis by activin A and follistatin.
Ventral prostate development occurs by branching morphogenesis and is an androgen-dependent process modulated by growth factors. Many growth factors have been implicated in branching morphogenesis including activins (dimers of beta(A) and beta(B) subunits); activin A inhibited branching of lung and kidney in vitro. Our aim was to examine the role of activins on prostatic development in vitro and their localization in vivo. Organ culture of day 0 rat ventral prostates for 6 days with activin A (+/- testosterone) inhibited prostatic branching and growth without increasing apoptosis. The activin-binding protein follistatin increased branching in vitro in the absence (but not presence) of testosterone, suggesting endogenous activins may reduce prostatic branching morphogenesis. In vivo, inhibin alpha subunit was not expressed until puberty, therefore inhibins (dimers of alpha and beta subunits) are not involved in prostatic development. Activin beta(A) was immunolocalized to developing prostatic epithelium and mesenchymal aggregates at ductal tips. Activin beta(B) immunoreactivity was weak during development, but was upregulated in prostatic epithelium during puberty. Activin receptors were expressed throughout the prostatic epithelium. Follistatin mRNA and protein were expressed throughout the prostatic epithelium. The in vitro evidence that activin and follistatin have opposing effects on ductal branching suggests a role for activin as a negative regulator of prostatic ductal branching morphogenesis.
Cancilla
B
B
Monash Institute of Reproduction and Development, Monash University, Clayton, Victoria, Australia.
Jarred
R A
RA
Wang
H
H
Mellor
S L
SL
Cunha
G R
GR
Risbridger
G P
GP
D029404:Activin Receptors; D028341:Activins; D000818:Animals; D038681:Follistatin; D006023:Glycoproteins / Q000032:analysis / Q000494:pharmacology*; D007150:Immunohistochemistry; D028322:Inhibin-beta Subunits; D007265:Inhibins / Q000032:analysis / Q000235:genetics / Q000494:pharmacology*; D008297:Male; D009024:Morphogenesis / Q000187:drug effects; D009924:Organ Culture Techniques; D010455:Peptides / Q000032:analysis; D011467:Prostate / Q000196:embryology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017978:Receptors, Growth Factor / Q000032:analysis
D038681:Follistatin; D006023:Glycoproteins; D010455:Peptides; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; C044147:activin B; C103008:inhibin beta A subunit; C094377:inhibin-alpha subunit; D028341:Activins; D007265:Inhibins; D028322:Inhibin-beta Subunits; D029404:Activin Receptors