EFFECTS OF ESTROGEN UPON NITRIC-OXIDE SYNTHASE NADPH-DIAPHORASE ACTIVITY IN THE HYPOTHALAMONEUROHYPOPHYSEAL SYSTEM OF THE RAT

An understanding of the interaction between oestrogen and the nitric o xide synthase/nitric oxide system is important for determining the rol es of nitric oxide in central nervous control of osmotic homeostasis a nd certain aspects of reproduction. The effects of oestrogen on nitric oxide synthase and nitric oxide synthase activity were investigated i n the magnocellular neurosecretory system. Ovariectomized female rats were injected subcutaneously with 17 beta-estradiol benzoate either 10 mu g daily for four days (short-term low-dose) or 200 mu g daily for 21 days (long-term high-dose). In the neurohypophysis the density of N ADPH-diaphorase staining-a marker for nitric oxide synthase activity-w as increased after both short-term low-dose and long-term high-dose es tradiol treatment, but no difference in nitric oxide synthase immunore activity was observed after either treatment. In the magnocellular sup raoptic and paraventricular nuclei, short-term low-dose oestrogen trea tment did not induce any detectable changes in nitric oxide synthase g ene expression, the proportion of nitric oxide synthase-immunoreactive neurons, or the proportion of NADPH-diaphorase-positive neurons. Long -term high-dose oestrogen treatment also had no effect on nitric oxide synthase gene expression or immunoreactivity, but caused a reduction of the proportion of NADPH-diaphorase-positive neurons in the supraopt ic nucleus and a reduction in the intensity of this histochemical stai ning. Qualitatively similar changes were observed in the magnocellular part of the paraventricular nucleus. The results provide, for the fir st time, evidence of a complex interaction between oestrogen and nitri c oxide synthase in the neuroendocrine system in which nitric oxide sy nthase activity is regulated differently in the magnocellular cell bod ies and axonal terminals and in which the activity of the enzyme rathe r than its expression is controlled. (C) 1998 IBRO. Published by Elsev ier Science Ltd.