Effects of oestrogen upon nitric oxide synthase NADPH-diaphorase activity in the hypothalamo-neurohypophysial system of the rat.
An understanding of the interaction between oestrogen and the nitric oxide synthase/nitric oxide system is important for determining the roles of nitric oxide in central nervous control of osmotic homeostasis and certain aspects of reproduction. The effects of oestrogen on nitric oxide synthase and nitric oxide synthase activity were investigated in the magnocellular neurosecretory system. Ovariectomized female rats were injected subcutaneously with 17beta-estradiol benzoate either 10 microg daily for four days (short-term low-dose) or 200 microg daily for 21 days (long-term high-dose). In the neurohypophysis the density of NADPH-diaphorase staining--a marker for nitric oxide synthase activity--was increased after both short-term low-dose and long-term high-dose estradiol treatment, but no difference in nitric oxide synthase immunoreactivity was observed after either treatment. In the magnocellular supraoptic and paraventricular nuclei, short-term low-dose oestrogen treatment did not induce any detectable changes in nitric oxide synthase gene 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 supraoptic nucleus and a reduction in the intensity of this histochemical staining. Qualitatively similar changes were observed in the magnocellular part of the paraventricular nucleus. The results provide, for the first time, evidence of a complex interaction between oestrogen and nitric oxide synthase in the neuroendocrine system in which nitric oxide synthase activity is regulated differently in the magnocellular cell bodies and axonal terminals and in which the activity of the enzyme rather than its expression is controlled.
Department of Human Anatomy, University of Oxford, UK.
H
H
Wang
J F
JF
Morris
D000818:Animals; D008058:Dihydrolipoamide Dehydrogenase / Q000378:metabolism*; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D007279:Injections, Subcutaneous; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D010052:Ovariectomy; D010053:Ovary / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000201:enzymology; D010904:Pituitary Gland, Posterior / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D020318:Rats, Long-Evans; D013495:Supraoptic Nucleus / Q000201:enzymology; D014158:Transcription, Genetic
D012333:RNA, Messenger; D004958:Estradiol; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D008058:Dihydrolipoamide Dehydrogenase