Cranial irradiation of female rats causes dose-dependent and age-dependentactivation or inhibition of pubertal development

Cranial irradiation in prepubertal children with leukemia or brain tumors c an lead to precocious or in high doses to late puberty. To unravel the unde rlying mechanisms, we developed a rat model with selective cranial Co-60-ir radiation technique. Infantile (12-16 d old) or juvenile (21-23 d old) fema le Sprague-Dawley rats received a single dose of 4, 5, 6, 9 or 2 x 9 Gy (at days 21 and 23). Each group consisted of 7-20 animals. High radiation dose s (9 Gy and more) caused retardation of sexual development, whereas low rad iation doses (5 or 6 Gy) led to accelerated onset of puberty in 20% of infa ntile irradiated rats animals as determined by vaginal opening. interesting ly, at peripubertal age (postnatal day 32-34), 5 or 6 Gy infantile irradiat ed rats had significantly higher serum LH levels stimulated by GnRH and est radiol levels (p < 0.05). 2 x 9 GY irradiated rats had at the age of 3 mo a marked growth retardation and significantly lower GH levels than the contr ols (p < 0.05) whereas prolactin, FSH, TSH, T-4, and corticosterone levels were comparable with controls. These studies demonstrate that the GnRH-puls e generator is very radiosensitive as precocious activation occurred after low dose irradiation (5 or 6 Gy) of infantile rats without any other endocr ine disorder. High radiation doses (9 or 2 x 9 Gy) induced retardation of s exual maturation and later on growth hormone deficiency. Moreover this mode l of cranial irradiation seems to be suitable to study the molecular mechan isms of radiation induced pubertal changes.