Reduction of γ-aminobutyric acid-ergic neurotransmission as a putative mechanism of radiation induced activation of the gonadotropin releasing-hormone-pulse generator leading to precocious puberty in female rats

Abstract

Brain irradiation in prepubertal children with malignomas can cause precocious puberty. A selective cranial cobalt (Co 60)-irradiation technique has been developed in rats. In two experiments early juvenile (13–15 days old) female rats received a single dose of 5 Gy or sham irradiation. At pubertal age (post-natal days 33–34) irradiated rats had higher serum estradiol and luteinizing hormone levels. In experiment 1 irradiated rats had higher gonadotropin releasing-hormone (GnRH) mRNA levels in the preoptic area compared to controls ( P<0.05). In experiment 2 the release rates of γ-aminobutyric acid (GABA) in vitro from preoptic mediobasal hypothalamic areas of irradiated rats were significantly reduced after stimulation with the GABA A receptor agonist muscimol (maximum values 4607±804 vs. 7399±1048 pM in controls, mean±SEM, P<0.05). Radiation induced central precocious puberty might be caused by damage to inhibitory GABAergic neurons leading to premature activation of the GnRH-pulse generator.