Androgen-mediated development of irradiation-induced thyroid tumors in rats: dependence on animal age during interval of androgen replacement in castrated males.
When male Long-Evans rats at age 8 weeks were radiation treated (40 microCi Na131I), thyroid follicular adenomas and carcinomas were observed at age 24 months with a high incidence of 94%. Castration of males prior to irradiation significantly reduced this tumor incidence to 60%. When testosterone (T) was replaced in castrated, irradiated male rats, differentially increased incidences of thyroid tumors occurred, depending on the time interval for hormone replacement. Immediate (age 2-6 mo) or early (age 6-12 mo) T replacement at approximate physiologic levels led to thyroid follicular tumor incidences of 100 and 82%, respectively, whereas intermediate (12-18 mo) or late (18-24 mo) T treatment led to only 70 and 73% incidences, respectively. Continuous T replacement (2-24 mo) in castrated irradiated male rats raised thyroid tumor incidence to 100%. Since elevated thyroid-stimulating hormone (TSH) is a reported requisite for development of radiation-associated thyroid tumors, the effects of T on serum TSH levels were examined. Mean serum TSH values in all irradiated animal groups were significantly elevated above age-matched nonirradiated animals at 6, 12, 18, and 24 months. Serum TSH levels were higher in continuous T-replaced irradiated castrates than in intact, irradiated males, whereas such intact male TSH levels were greater than those for irradiated castrates without T treatment. Interval T replacement in castrated male rats was generally associated with increased serum TSH levels during the treatment interval and with lowered TSH levels after discontinuation of T treatment, particularly in irradiated rats. However, when irradiated, castrated males received late T replacement (age 18-24 mo), there was no elevation of TSH at the end of the treatment interval. Thus an indirect effect of T via early stimulation of TSH may be at least partly responsible for the high incidence of irradiation-induced thyroid tumors in rats.
Hofmann
C
C
Oslapas
R
R
Nayyar
R
R
Paloyan
E
E
D000367:Age Factors; D000728:Androgens / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D002369:Castration; D003043:Cocarcinogenesis; D003692:Delayed-Action Preparations; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000209:etiology*; D009381:Neoplasms, Radiation-Induced / Q000097:blood / Q000209:etiology* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000473:pathology; D051381:Rats; D012669:Seminal Vesicles / Q000473:pathology; D013964:Thyroid Neoplasms / Q000097:blood / Q000209:etiology* / Q000473:pathology; D013972:Thyrotropin / Q000097:blood
D000728:Androgens; D003692:Delayed-Action Preparations; D013972:Thyrotropin