Chronic-Intermittent Cold Stress in Rats Induces Selective Ovarian Insulin Resistance1

Mauricio Dorfman, Victor D. Ramirez, Elisabet Stener-Victorin, Hernan E. Lara
2009 Biology of Reproduction  
In rat ovary chronic cold stress increases sympathetic nerve activity, modifies follicular development, and initiates a polycystic condition. To see whether there is a relationship between the previously described changes in follicular development and metabolic changes similar to those in women with polycystic ovary, we have studied the effect of chronic cold stress (48C for 3 h/day, Monday to Friday, for 4 wk) on insulin sensitivity and the effect of insulin on sympathetic ovarian activity.
more » ... hough coldstressed rats ate more than the controls, they did not gain more weight. Insulin sensitivity, determined by hyperinsulinemiceuglycemic clamp, was significantly increased in the stressed animals. Insulin in vitro increased the basal release of norepinephrine from the ovaries of control rats but not from those of stressed rats, suggesting a local neural resistance to insulin in stressed rats. The levels of mRNA and protein for IRS1 and SLC2A4 (also known as GLUT4), molecules involved in insulin signaling, decreased significantly in the ovaries but not in the muscle of stressed rats. This decrease was preferentially located in theca-interstitial cells compared with granulosa cells, indicating that theca cells (the only cells directly innervated by sympathetic nerves) are responsible for the ovarian insulin resistance found in stressed rats. These findings suggest that ovarian insulin resistance produced by chronic stress could be in part responsible for the development of the polycystic condition induced by stress. catecholamines, insulin, insulin resistance, ovary, polycystic ovary, stress 1 Supported by Fondecyt grant 1050765 to H.E.L. and Conicyt project 24060026 to partially support a PhD thesis to M.D. M.D. is recipient of a PhD fellowship from Conicyt.
doi:10.1095/biolreprod.108.070904 pmid:18923160 fatcat:z36xrrgec5fhxgpctpshhyop3m