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

Brain irradiation in prepubertal children with malignomas can cause precoci ous puberty. A selective cranial cobalt (Co-60)-irradiation technique has b een developed in rats. In two experiments early juvenile (13-15 days old) f emale 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 gona dotropin releasing-hormone (GnRH) mRNA levels in the preoptic area compared to controls (P < 0.05). In experiment 2 the release rates of <gamma>-amino butyric 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 +/- 104 8 pM in controls, mean +/- SEM, P < 0.05). Radiation induced central precoc ious puberty might be caused by damage to inhibitory GABAergic neurons lead ing to premature activation of the GnRH-pulse generator. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.