Reduction of gamma-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.
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 gamma-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.
Roth
C
C
Children's Hospital, University of, Göttingen, Germany. croth@med.uni-goettingen.de
Schmidberger
H
H
Lakomek
M
M
Witt
O
O
Wuttke
W
W
Jarry
H
H
D000818:Animals; D005260:Female; D015870:Gene Expression / Q000502:physiology / Q000528:radiation effects; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism / Q000528:radiation effects*; D007031:Hypothalamus / Q000378:metabolism / Q000528:radiation effects*; D009474:Neurons / Q000378:metabolism / Q000528:radiation effects*; D010902:Pituitary Gland / Q000378:metabolism / Q000528:radiation effects*; D011629:Puberty, Precocious / Q000209:etiology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism / Q000528:radiation effects; D051381:Rats; D009435:Synaptic Transmission / Q000528:radiation effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000528:radiation effects*
D012333:RNA, Messenger; D007987:Gonadotropin-Releasing Hormone; D005680:gamma-Aminobutyric Acid