title: Ovarian hormone modulation of radiation-induced cataractogenesis: dose-response studies.
abstract: OBJECTIVE
  Epidemiologic data on the effects of female sex hormones in cataract formation are conflicting. With the use of a rat model of radiation-induced cataractogenesis, it was found that estrogen can either enhance or inhibit the progression of radiation cataracts, depending on when the hormone is administered. The present study was performed to further define radiation-hormone interactions during cataractogenesis.
  
  
  METHODS
  In one experiment, rats were left ovary-intact or ovariectomized and were then irradiated with 2.5, 5, 10, or 15 Gy to one eye. In another experiment, ovariectomized rats were treated continuously with three different doses of estradiol through a slow-release capsule implanted subcutaneously, after which one eye was irradiated with 15 Gy. In all animals, cataract formation was followed by slit lamp examination at regular intervals.
  
  
  RESULTS
  Latency to identification of cataracts decreased exponentially with increasing radiation dose. The presence of ovaries enhanced cataractogenesis when the eye was irradiated with 15 Gy, but there was no difference between ovary-intact and ovariectomized rats that were irradiated at lower doses. In ovariectomized rats irradiated with 15 Gy, estradiol increased the rate of progression of cataracts in a dose-dependent manner. The rate of cataract progression increased linearly with increasing estradiol dose; there was no sign of saturation at high estradiol doses, as would be expected from a receptor-mediated effect.
  
  
  CONCLUSIONS
  Ovarian hormones enhance radiation-induced cataract formation; hormone supplementation experiments indicate that estrogen is responsible for this effect. The data suggest that the enhancing effect of estradiol is not mediated by its receptor, but this requires further study.
authors.affiliation: Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Bigsby
authors.forename: Shailaja
authors.initials: S
authors.lastname: Valluri
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lopez
authors.forename: Marc S
authors.initials: MS
authors.lastname: Mendonca
authors.forename: Andrea
authors.initials: A
authors.lastname: Caperell-Grant
authors.forename: Colleen
authors.initials: C
authors.lastname: DesRosiers
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Dynlacht
mesh_terms: D000818:Animals; D002386:Cataract / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D004307:Dose-Response Relationship, Radiation; D004958:Estradiol / Q000008:administration & dosage; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects*; D007908:Lens, Crystalline / Q000528:radiation effects*; D010052:Ovariectomy; D010053:Ovary / Q000502:physiology*; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004967:Estrogens; D004958:Estradiol