17Beta-estradiol confers a protective effect against transforming growth factor-beta2-induced cataracts in female but not male lenses.
Transforming growth factor-beta2 (TGF-beta2) induces anterior subcapsular cataracts, with a marked increase in cytoskeletal and extracellular matrix proteins, such as alpha-smooth muscle actin (alphaSMA). It has been shown that 17beta-estradiol (E2) can prevent TGF-beta2-induced cataracts in lenses from ovariectomized female rats. The purpose of the current study was to extend this finding by testing whether E2 can prevent TGF-beta2-induced cataracts and inhibit the induction of alphaSMA gene expression in normal male and normal, non-ovariectomized female rats.Sex-specific differences were observed in 17-week-old rat lenses incubated in 0.15 ng ml(-1) TGF-beta2 and in 10(-8)M E2 plus TGF-beta2. TGF-beta2 induced approximately twice as many anterior subcapsular plaques and 1.5 times the level of alphaSMA transcripts in male lenses compared to female lenses. Notably, E2 inhibited plaque formation and the induction of alphaSMA transcripts in female rat lenses but not in male rat lenses. E2 also inhibited the induction of alphaSMA in TGF-beta2-incubated lenses from ovariectomized female rats.E2 prevented lens opacification and the induction of alphaSMA gene expression in female, but not male, lenses. This sex-specific difference may have implications for studies on the therapeutic use of estradiol for treatment of secondary cataract.
Chen
Zhengguang
Z
Section on Molecular Therapeutics, Building 6, Room 232, National Eye Institute, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA.
John
Molykutty
M
Subramanian
Saradha
S
Chen
Hong
H
Carper
Deborah
D
D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D002386:Cataract / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007908:Lens, Crystalline / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009924:Organ Culture Techniques; D010052:Ovariectomy; D051381:Rats; D012737:Sex Factors; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000633:toxicity*; D053781:Transforming Growth Factor beta2
D000199:Actins; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D004958:Estradiol