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Submitted on September 11, 2007
Accepted on February 19, 2008
Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, and Laboratório de Neuroendocrinologia, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brasil; Departamento de Bioquímica y Biología Molecular-Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile
* To whom correspondence should be addressed. E-mail: hlara{at}ciq.uchile.cl.
Previous reports about the rat ovary have shown that cold stress promotes ovarian morphological alterations related to a polycystic ovary (PCO) condition through activation of the ovarian sympathetic nerves. Since the noradrenergic nucleus locus coeruleus (LC) is activated by cold stress and synaptically connected to the preganglionic cell bodies of the ovarian sympathetic pathway, this study aimed to evaluate LC's role in cold stress-induced PCO in rats. Ovarian morphology, endocrine and sympathetic functions were evaluated after 8 weeks of chronic intermittent cold stress (4 °C, 3h/day) in rats with or without LC lesion. The effect of acute and chronic cold stress upon the LC neurons activity was confirmed by Fos protein expression in tyrosine hydroxylase (TH)-immunoreactive (ir) neurons. Cold stress induced the formation of follicular cysts, type III follicles and follicles with hyperthecosis, alongside increased plasma estradiol and testosterone levels, irregular estrous cyclicity and reduced ovulation. Considering estradiol release in vitro, cold stress potentiated the ovarian response to human chorionic gonadotropin. Ovarian norepinephrine (NE) was not altered after 8 weeks of stress. However, LC lesion reduced NE activity in the ovary of cold-stressed rats, but not in controls, and prevented all the cold stress effects evaluated. Cold stress increased the number of Fos/TH-ir neurons in the LC, but this effect was more pronounced for acute stress as compared to chronic stress. These results show that cold stress promotes PCO in rats, which apparently depends on ovarian NE activity that, under this condition, is regulated by the noradrenergic nucleus LC.
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