LH-RELEASE IN OVARIECTOMIZED RATS IS MAINTAINED WITHOUT NORADRENERGIC NEUROTRANSMISSION IN THE PREOPTIC ANTERIOR HYPOTHALAMIC AREA - EXTREME FUNCTIONAL PLASTICITY OF THE GNRH PULSE-GENERATOR

Norepinephrine (NE) in the preoptic/anterior hypothalamic area (PO/AH) is known to be involved in the regulation of luteinizing hormone (LH) secretion. The effects of selective and complete depletion of NE in the PO/AH of ovariectomized (ovx) rats on LH secretion were studied. PO/AH concentrations of NE were reduced by 90% within 6 h and were undetectable (more than 98% depletion) 52 h after bilateral stereotaxic microinjections of 50-mu-g of 5-amino-2,4-dihydroxy-alpha-methylphenylethylamine (5-ADMP). LH levels in the blood were significantly reduced within 60 min after NE depletion but remained low only for several hours. Despite continuously low preoptic NE concentrations episodic LH secretion reoccurred within 4-6 h such that normal blood LH levels were present 6 and 52 h after selective NE depletion. While the alpha-1-adrenoreceptor antagonist prazosin was inhibitory to LH secretion in control rats the drug was totally ineffective in the NE depleted animals. NE may be inhibitory to LH secretion via a beta-adrenergic receptor mechanism. It was therefore also tested whether 5-ADMP causes a massive NE release which might be inhibitory to LH secretion. Propranolol (PROP), a beta-adrenoreceptor blocking drug, was given 30 min prior to preoptic injection of 5-ADMP. Blockade of beta-receptors did not prevent the transient inhibition of LH release. These results indicate that under physiologic conditions the GnRH pulse generator functions only properly when NE is present in the PO/AH and that the stimulatory effect of NE is mediated via an alpha-1-adrenoreceptor. Within few hours after preoptic NE depletion LH secretion restored and another non alpha-1-receptor mechanism is involved in driving the gonadotropin releasing hormone (GnRH) pulse generator.