Differential radiosensitivity of hypothalamo-pituitary function in the young adult rat

Cranial irradiation ill children and adults often results in irreversible h ypopituitarism. The earliest and most common endocrine abnormality is GH de ficiency, often followed by other pituitary hormone deficits. We investigat ed whether a similar pattern of progressive hypopituitarism could be reprod uced in art animal model. Different doses of cranial irradiation were deliv ered to the hypothalamo-pituitary region of normal adult male rats, wand th e effects on their subsequent growth, pituitary weight and hormone contents were studied. Animals received cranial irradiation with 300 kV X-rays at d oses of 0, 20, 22 or 24 Gy (n = 15 per group) and five animals from each gr oup were killed at 8, 14 or 20 weeks after irradiation. Their anterior pitu itary glands were weighed and assayed for GH, LH, TSH, ACTH and prolactin ( PRL) content. All three doses of irradiation reduced body weight compared w ith that in non-irradiated controls andcompromised growth between 8 and 20 weeks. Pituitary weight increased between 8 and 20 weeks in control rats, w hereas it decreased significantly in the irradiated animals. Irradiation in duced time- and dose-dependent changes in pituitary hormone contents. GH an d PRL were most sensitive and decreased by more than 90% after irradiation; TSH contents were unaffected 8 weeks after the lowest dose of irradiation, but were reduced at 14 and 20 weeks. LH and ACTH were the slowest to be af fected, and only at the greater doses of radiation. Thus progressive multip le pituitary endocrine deficits can be induced differentially in rats by in creasing doses of cranial irradiation. This model should prove useful for d efining the sites and mechanisms by which cranial irradiation induces neuro endocrine dysfunction.