IS THE INHIBITORY-ACTION OF ESTRADIOL ON LUTEINIZING-HORMONE PULSE FREQUENCY IN ANESTROUS EWES MEDIATED BY NORADRENERGIC NEURONS IN THE PREOPTIC AREA

This study tested the hypothesis that estradiol inhibits luteinizing h ormone (LH) pulse frequency in anestrous ewes by increasing the activi ty of an inhibitory noradrenergic (NE) system that acts in the ovine p reoptic area (POA). The effects of estradiol on the release of NE and other neurotransmitters in the POA were determined using intracranial microdialysis. Microdialysis probes (5 mm membrane length) were insert ed via chronic guide tubes into the POA. Ringer's solution was pumped through the probes at a rate of 2 mu l/min for 8 h, the alpha-adrenerg ic antagonist phenoxybenzamine (PBZ; 60 mu g/ml of Ringer's solution) was then administered via the probe from hours 8 to 12, and Ringer's s olution alone was given the last 4 h. The outflow from the dialysis pr obes was collected every 20 min from 2 to 16 h and concentrations of a minergic transmitters and gamma aminobutyric acid determined by high-p erformance liquid chromatography. Blood samples were collected every 1 0 min throughout the experiment and the LH pulse patterns determined. Dialysis was done in the same neural area twice in each ewe, without ( ovariectomy only) and with estadiol treatment (ovariectomy and a 1.5-c m-long Silastic capsule filled with crystalline estradiol placed subcu taneously for 2 days); the order of dialysis was randomized. As expect ed, estradiol decreased the LH pulse frequency. This negative feedback action of estradiol was associated with a decrease in mean NE concent rations in dialysate samples and an increase in the intraanimal variab ility of NE. Estradiol had no effect on any other neurotransmitter mea sured. Perfusion of PBZ through the dialysis probe increased NE levels , presumably by blocking adrenergic autoreceptors. However, this effec t was only observed when the probes were located rostral to the decuss ation of the anterior commissure. Thus the autoregulatory control of N E release appears to vary in different hypothalamic areas. PBZ signifi cantly increased the LH pulse amplitude, independently of any effects on NE release, raising the possibility that noradrenergic neurons act via a-adrenergic receptors to inhibit the LH pulse amplitude. In concl usion, these data demonstrate that estradiol decreases the mean NE lev els in the POA of anestrous ewes, but may increase its episodic releas e.