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Locus Coeruleus Mediates Cold Stress-Induced Polycystic Ovary in Rats

Departamento de Fisiologia (M.P.B., C.M.L.), Faculdade de Medicina de Ribeirão Preto and Laboratório de Neuroendocrinologia (R.E.S., C.V.V.H., J.A.A.-F.), Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, 14049-900 São Paulo, Brasil; and Departamento de Bioquímica y Biología Molecular-Facultad de Ciencias Químicas y Farmacéuticas (H.E.L.), Universidad de Chile, 837-0459 Santiago, Chile

Address all correspondence and requests for reprints to: Hernán E. Lara, Departamento de Bioquímica y Biología Molecular-Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, P.O. Box 233, Santiago, Chile. 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. Because 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 the LC’s role in cold stress-induced PCO in rats. Ovarian morphology and endocrine and sympathetic functions were evaluated after 8 wk of chronic intermittent cold stress (4 C, 3 h/d) in rats with or without LC lesion. The effect of acute and chronic cold stress upon the LC neuron activity was confirmed by Fos protein expression in tyrosine hydroxylase-immunoreactive 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 wk 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/tyrosine hydroxylase-immunoreactive neurons in the LC, but this effect was more pronounced for acute stress as compared with 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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