Hypothalamic changes in norepinephrine release in rats with estradiol valerate-induced polycystic ovaries.
Chronic anovulation and polycystic ovaries (PCO) can be induced by a single i.m. injection of estradiol valerate (EV, 2 mg in oil) in the rat. Constant exposure to high plasma levels of estradiol provokes a neurotoxic effect on the hypothalamic neurons, including those from the arcuate nucleus. Because of the important participation of hypothalamic norepinephrine (NE) in the regulation of GnRH release and the possible noxious effect of prolonged exposure of these neurons to estradiol, our interest was to study the activity of the noradrenergic neurons innervating the hypothalamus. We analyzed the biosynthesis, content, and release of NE from the noradrenergic nerve terminals of the hypothalamus during the PCO condition. We found a decrease in tyrosine hydroxylase (TH) activity and in the content of dopamine (DA) in the anterior hypothalamus after 2 mo of EV injection, whereas dopamine-beta-hydroxylase (D beta H) was increased without changes in NE content. No variations in TH activity or in DA and NE contents in the medial hypothalamus were observed, but a decrease in D beta H activity was evident. After 2 mo of EV administration, an increase in the electrically induced release of NE from anterior hypothalamic blocks incubated in vitro was detected; this effect was not evidenced in the medial hypothalamus. After 5 mo of EV administration, release of NE increased in anterior hypothalamic blocks but decreased in medial hypothalamic tissue. The inhibitory effect of morphine on NE release found in control animals was increased in the hypothalamus from PCO rats, suggesting an increased number of mu-opioid binding sites in noradrenergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
Luza
S M
SM
Department of Biochemistry and Molecular Biology, Faculty of Chemistry and Pharmaceutical Sciences, Universidad de Chile, Santiago.
Lizama
L
L
Burgos
R A
RA
Lara
H E
HE
D000818:Animals; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D007031:Hypothalamus / Q000187:drug effects / Q000503:physiopathology*; D007032:Hypothalamus, Anterior / Q000187:drug effects / Q000378:metabolism; D007033:Hypothalamus, Middle / Q000187:drug effects / Q000378:metabolism; D009020:Morphine / Q000494:pharmacology; D009638:Norepinephrine / Q000096:biosynthesis / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000139:chemically induced / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014316:Tritium
D014316:Tritium; D004958:Estradiol; D009020:Morphine; D009638:Norepinephrine