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Nitric Oxide Plays an Important Role in the Diurnal Change of Tuberoinfundibular Dopaminergic Neuronal Activity and Prolactin Secretion in Ovariectomized, Estrogen/Progesterone-Treated Rats¹

Department of Physiology, School of Life Science, National Yang-Ming University, Taipei, Taiwan 11221

Address all correspondence and requests for reprints to: Jenn-Tser Pan, Ph.D., Department of Physiology, National Yang-Ming University, Taipei, Taiwan 11221.

A significant diurnal change of tuberoinfundibular dopaminergic (TIDA) neuronal activity coincident with the estrogen (E₂)-induced afternoon PRL surge has been reported in ovariectomized, E₂-primed (OVX+E₂) rats. Systemic injection of a nitric oxide (NO) synthase (NOS) inhibitor, N^G-nitro-L-arginine (L-NA, 50 mg/kg, ip at 1000 and 1200 h), significantly blocked the diurnal changes of TIDA neuronal activity and PRL secretion at 1500 and 1700 h in OVX+E₂ rats. Coadministration of L-arginine (300 mg/kg, ip) with L-NA completely prevented the effects of L-NA. Total nitrite/nitrate levels in the serum of L-NA- and L-NA+L-arginine-treated rats substantiated the effects of L-NA and L-arginine on NO production. Pretreatment of antisense oligodeoxynucleotide (ODN; 1 µg/3 µl; intracerebroventricularly at 48, 24, and 7 h before sacrifice) against the messenger RNA (mRNA) of constitutive NOS, i.e. neuronal NOS or endothelial NOS, was also effective in preventing the diurnal changes of TIDA neuronal activity and PRL surge at 1500 h. The same treatment of antisense ODN against the mRNA of inducible NOS, i.e. macrophage NOS, had no effect.

Progesterone (P₄) has been reported to advance and augment the diurnal changes of TIDA neuronal activity and the afternoon PRL surge, by 1 h, in both proestrous and OVX+E₂ 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 P₄ on TIDA neurons and serum PRL at 1300 h, which effect could be negated by simultaneous administration of L-arginine (300 mg/kg, ip). Pretreatment with antisense ODNs against the mRNA of neuronal NOS or endothelial NOS, but not macrophage NOS, was also effective in preventing the P₄’s effect on TIDA neuronal activity and PRL secretion at 1300 h. In summary, NO may play a physiological role in the E₂- and P₄-regulated diurnal changes of TIDA neuronal activity and PRL secretion.

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