Intracerebroventricular administration of copper-zinc superoxide dismutase inhibits 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 has been demonstrated that structural and functional analogs of copper-zinc superoxide dismutase (Cu,Zn-SOD) inhibit neuronal NOS. The present study examined 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 unanesthetized, freely moving, ovariectomized (OVX) ewes. Jugular blood samples were taken every 15 min for 5 h before and 8 h after i.c.v. injections. In a pilot trial using three OVX ewes, i.c.v. injection of Cu,Zn-SOD at a dose of 0.5, 1.0 or 2.0 microg in 100 microl saline decreased plasma LH levels and abolished LH pulses, without affecting FSH secretion. In the main experiment, i.c.v. injection of 100 microl saline had no effect on mean LH levels and LH pulse frequency, whereas i.c.v. injection of Cu,Zn-SOD at a dose of 1 microg/100 microl saline significantly (P < 0.01) decreased mean LH levels and LH pulse frequency. In conclusion, this study provides the first evidence for the role of Cn,Zn-SOD in the control of LH secretion at the level of the brain in female mammals.