Nitric oxide plays an important role in the diurnal change of tuberoinfundibular dopaminergic neuronal activity and prolactin secretion in ovariectomized, estrogen/progesterone-treated rats

A significant diurnal change of tuberoinfundibular dopaminergic (TIDA) neur onal activity coincident with the estrogen (E-2)-induced afternoon PRL surg e has been reported in ovariectomized, E-2-primed (OVX+E-2) rats. Systemic injection of a nitric oxide (NO) synthase (NOS) inhibitor, N-G-nitro-L-argi nine (L-NA, 50 mg/kg, ip at 1000 and 1200 h), significantly blocked the diu rnal changes of TIDA neuronal activity and PRL secretion at 1500 and 1700 h in OVX+E-2 rats. Coadministration of L-arginine (300 mg/kg, ip) with L-NA completely prevented the effects of L-NA. Total nitrite/nitrate levels in t he serum of L-NA- and L-NA+L-arginine-treated rats substantiated the effect s of L-NA and L-arginine on NO production. Pretreatment of antisense oligod eoxynucleotide (ODN; 1 mu g/3 mu l; intracerebroventricularly at 48, 24, an d 7 h before sacrifice) against the messenger RNA (mRNA) of constitutive NO S, i.e. neuronal NOS or endothelial NOS, was also effective in preventing t he diurnal changes of TIDA neuronal activity and PRL surge at 1500 h. The s ame treatment of antisense ODN against the mRNA of inducible NOS, i.e. macr ophage NOS, had no effect. Progesterone (P-4) has been reported to advance and augment the diurnal cha nges of TIDA neuronal activity and the afternoon PRL surge, by 1 h, in both proestrous and OVX+E-2 rats. We further showed that L-NA dose dependently (50 but not 5 mg/kg, ip at 1000 and 1200 h) blocked the effect of P-4 on TI DA neurons and serum PRL at 1300 h, which effect could be negated by simult aneous administration of L-arginine (300 mg/kg, ip). Pretreatment with anti sense ODNs against the mRNA of neuronal NOS or endothelial NOS, but not mac rophage NOS, was also effective in preventing the P-4's effect on TIDA neur onal activity and PRL secretion at 1300 h. In summary, NO may play a physio logical role in the E-2- and P-4-regulated diurnal changes of TIDA neuronal activity and PRL secretion.