Intracerebroventricular administration of copper-zinc superoxide dismutaseinhibits pulsatile luteinizing hormone secretion in ovariectomized ewes

Intracerebroventricular (i.c.v.) injection of an inhibitor of nitric oxide synthase (NOS) abolishes pulsatile luteinizing hormone (LH) secretion. It h as been demonstrated that structural and functional analogs of copper-zinc superoxide dismutase (Cu,Zn-SOD) inhibit neuronal NOS. The present study ex amined the ability of Cu,Zn-SOD to affect pulsatile LH release in the ewe. Bovine Cu,Zn-SOD was administrated into the third cerebral ventricle of una nesthetized, freely moving, ovariectomized (OVX) ewes. Jugular blood sample s were taken every 15 min for 5 h before and 8 h after i.c.v. injections. I n a pilot trial using three OVX ewes, i.c.v, injection of Cu,Zn-SOD at a do se of 0.5, 1.0 or 2.0 mu g in 100 mu l saline decreased plasma LH levels an d abolished LH pulses, without affecting FSH secretion. In the main experim ent, i.c.v. injection of 100 mu l Saline had no effect on mean LH levels an d LH pulse frequency, whereas i.c.v. injection of Cu,Zn-SOD at a dose of 1 mu g/100 mu l saline significantly (P < 0.01) decreased mean LH levels and LH pulse frequency. In conclusion, this study provides the first evidence f or the role of Cn,Zn-SOD in the control of LH secretion at the level of the brain in female mammals. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.