Oxygen tension modulates TGF-beta(1) expression and PGE production in human corpus cavernosum smooth muscle cells

Transforming growth factor-beta(1) (TGF-beta(1)) induces fibrillar collagen synthesis in human corpus cavernosum smooth muscle cells (HCC SMC). TGF-be ta(1) also induces TGF-beta(1) mRNA expression as well as TGF-beta receptor s on HCC SMC, Prostaglandin E-1 (PGE(1)) suppresses TGF-beta(1) effects on HCC SMC, The aim of this study was to determine if HCC SMC synthesize PGE a nd if TGF-beta(1) expression and PGE synthesis are modulated by the oxygen tension. Both PGE and TGF-beta(1) were synthesized by HCC SMC in vitro. Red uced oxygen tensions consistent with in vivo penile flaccidity (30 mm Hg PO 2) inhibited PGE synthesis by 68% and induced TGF-beta(1) mRNA by two to th ree fold. Examination of corporal tissue biopsies by immunohistochemistry s taining revealed TGF-beta(1) limited to myocytes, with intense cytoplasmic immunoreactivity, These results are consistent with a PGE:TGF-beta(1) parad igm; that is, PGE and TGF-beta(1) modulate each other to regulate collagen synthesis in human corpus cavernosum smooth muscle, Synthesis of PGE is fav ored at increased oxygen tension, conditions that suppress TGF-beta(1) prod uction and collagen synthesis, whereas reduced oxygen tension inhibits pros tanoid production and favors TGF-beta(1) and collagen synthesis. Because fu nctional erectile tissue depends on the smooth muscle/connective tissue rat io, the advent of therapeutic PGE(1) would suggest a potential prophylactic means of maintaining a functional collagen/smooth muscle balance.