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Am J Physiol Endocrinol Metab 289: E391-E402, 2005. First published April 5, 2005; doi:10.1152/ajpendo.00531.2004
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Gonadotropin regulation of glutamate cysteine ligase catalytic and modifier subunit expression in rat ovary is subunit and follicle stage specific

Miyun Tsai-Turton1 and Ulrike Luderer1,2,3

Departments of 1Community and Environmental Medicine, 2Medicine, and 3Developmental and Cell Biology, University of California at Irvine, Irvine, California

Submitted 4 November 2004 ; accepted in final form 26 March 2005

We have observed that levels of the antioxidant glutathione (GSH) and protein levels of the catalytic and modifier subunits of the rate-limiting enzyme in GSH synthesis, GCLc and GCLm, increase in immature rat ovaries after treatment with gonadotropin. The goals of the present studies were to delineate the time course and intraovarian localization of changes in GSH and GCL after pregnant mare's serum gonadotropin (PMSG) and after an ovulatory gonadotropin stimulus. Twenty-four hours after PMSG, there was a shift from predominantly granulosa cell expression of gclm mRNA, and to a lesser extent gclc, to predominantly theca cell expression. GCLc immunostaining increased in granulosa and theca cells and in interstitial cells. Next, prepubertal female rats were primed with PMSG, followed 48 h later by 10 IU of hCG. GCLm protein and mRNA levels increased dramatically from 0 to 4 h after hCG and then declined rapidly. There was minimal change in GCLc. The increase in gclm mRNA expression was localized mainly to granulosa and theca cells of preovulatory follicles. To verify that GCL responds similarly to an endogenous preovulatory gonadotropin surge, we quantified ovarian GCL mRNA levels during the periovulatory period in adult rats. gclm mRNA levels increased after the gonadotropin surge on proestrus and then declined rapidly. Finally, we assessed the effects of gonadotropin on ovarian GCL enzymatic activity. GCL enzymatic activity increased significantly at 48 h after PMSG injection and did not increase further after hCG. These results demonstrate that gonadotropins regulate follicular GCL expression in a follicle stage-dependent manner and in a GCL subunit-dependent manner.

glutathione; {gamma}-glutamylcysteine synthetase; preovulatory gonadotropin surge



Address for reprint requests and other correspondence: U. Luderer, Center for Occupational and Environmental Health, Univ. of California, Irvine, 5201 California Ave., Suite 100, Irvine, CA 92617 (e-mail: uluderer{at}uci.edu)







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