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Experimental Biology and Medicine 226:701-706 (2001)
© 2001 Society for Experimental Biology and Medicine


ORIGINAL ARTICLE

GnRH and Gonadotropin Release Is Decreased in Chronic Nitric Oxide Deficiency

Maria J. Barnes*, Karen Lapanowski*, Jose A. Rafols{dagger}, David M. Lawson* and Joseph C. Dunbar*,1

* Department of Physiology and
{dagger} Department of Anatomy, Wayne State University School of Medicine, Detroit,Michigan48201

Nitric oxide synthetase (NOS), the conversion enzyme for nitric oxide (NO) is localized in the anterior pituitary of female rats, particularly in gonadotrophs and folliculo-stellate cells, suggesting that NO regulates the release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the anterior pituitary. The focus of this study was to determine the effect of chronic NO deficiency on the subsequent pituitary release of LH and FSH in vitro and the hypothalamic immunoexpression of GnRH in vivo. NO deficiency was induced by adding the NOS inhibitor, N-nitro-L-arginine (L-NNA, 0.6g/L) to the drinking water of female Wistar rats. After 8 weeks, the animals were euthanized, the pituitaries were removed, and they were incubated in vitro. Pituitaries were perfused for 4 hr in the presence of pulsatile gonadotropin release hormone (GnRH, 500 ng/pulse) every 30 min. S-Nitroso-L-acetyl penicillamine (SNAP, an NO donor, 0.1 mM) or L-nitro-argine methyl ester (L-NAME, a NOS inhibitor, 0.1 mM) was added to the media and perfusate samples were collected at 10-min intervals. LH and FSH levels in the perfusate were measured by double antibody radioimmunoassays. Pituitaries from the NO-deficient rats had a significantly smaller GnRH-stimulated release of LH and FSH compared with proestrous control rats. The addition of S-NAP to the perfusate resulted in decreased LH and FSH secretion in the control group, but increased LH secretion in the NO-deficient group. The addition of L-NAME to the perfusate suppressed LH secretion from control pituitaries, but not in pituitaries from NO-deficient animals. Immunohistochemistry of brain slices demonstrated that NO-deficient rats had a large qualitative decrease of GnRH in the median eminence compared with their controls. This decrease was particularly evident in the external capillary plexus of the median eminence. We concluded that chronic NO deficiency is associated with a decreased GnRH in neurosecretory terminals in the external capillary layer of the median eminence, accompanied by a decrease in LH and FSH release from the pituitaries.

Key Words: nitric oxide • luteinizing hormone • follicle stimulating hormone • gonadotropin




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M. J. Barnes, K. Lapanowski, J. A. Rafols, D. M. Lawson, and J. C. Dunbar
Chronic Nitric Oxide Deficiency Is Associated with Altered Leutinizing Hormone and Follicle-Stimulating Hormone Release in Ovariectomized Rats
Experimental Biology and Medicine, October 1, 2002; 227(9): 817 - 822.
[Abstract] [Full Text] [PDF]




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