HYPOTHALAMIC CHANGES IN NOREPINEPHRINE RELEASE IN RATS WITH ESTRADIOLVALERATE-INDUCED POLYCYSTIC OVARIES

Chronic anovulation and polycystic ovaries (PCO) can be induced by a s ingle i.m. injection of estradiol valerate (EV, 2 mg in oil) in the ra t. Constant exposure to high plasma levels of estradiol provokes a neu rotoxic effect on the hypothalamic neurons, including those from the a rcuate nucleus. Because of the important participation of hypothalamic norepinephrine (NE) in the regulation of GnRH release and the possibl e noxious effect of prolonged exposure of these neurons to estradiol, our interest was to study the activity of the noradrenergic neurons in nervating the hypothalamus. We analyzed the biosynthesis, content, and release of NE from the noradrenergic nerve terminals of the hypothala mus during the PCO condition. We found a decrease in tyrosine hydroxyl ase (TH) activity and in the content of dopamine (DA) in the anterior hypothalamus after 2 mo of EV injection, whereas dopamine-beta-hydroxy lase (D beta H) was increased without changes in NE content. No variat ions in TH activity or in DA and NE contents in the medial hypothalamu s were observed, but a decrease in D beta H activity was evident. Afte r 2 mo of EV administration, an increase in the electrically induced r elease of NE from anterior hypothalamic blocks incubated in vitro was detected; this effect was not evidenced in the medial hypothalamus. Af ter 5 mo of EV administration, release of NE increased in anterior hyp othalamic blocks but decreased in medial hypothalamic tissue. The inhi bitory effect of morphine on NE release found in control animals was i ncreased in the hypothalamus from PCO rats, suggesting an increased nu mber of mu-opioid binding sites in noradrenergic neurons. Together the se data indicate increased noradrenergic activity of the nerve termina ls from the anterior hypothalamus and decreased activity from catechol aminergic nerve terminals from the medial hypothalamus during PCO. The se results agree with similar findings described in women with PCO syn drome as suggested from the analysis of urinary catecholamines metabol ites, and gives further support for the involvement of central catecho lamines in the maintenance of the syndrome in mammals.