Di-(2-ethylhexyl) phthalate (DEHP) and its metabolite mono-(2-ethylhexyl) phthalate (MEHP) have been classified as toxicants to the reproductive system at the testis level and DEHP may also impair reproductive axis function at the pituitary levels. However, MEHP is 10-fold more potent than DEHP in toxicity and little is known about the toxicological effect of MEHP on pituitary. In this study, we demonstrated that 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD2), not 11 beta-HSD1, is strongly expressed in murine gonadotrope L beta T2 cells. Interestingly, MEHP inhibited Hsd11b2 mRNA level and 11 beta-HSD2 enzyme activity in L beta T2 cells at as low as 10(-7) M. Corticosterone (CORT) at a concentration of 10(-6) M significantly inhibited L beta T2 cell proliferation after 2-day Culture, and 10(-6) M RU486, an antagonist of glucccorticoid receptor (GR), reversed this inhibition. However, in the presence of 10(-5) or 10(-4) M MEHP, the minimal concentration of CORT to inhibit the proliferation of L beta T2 cells was lowered to 10(-7) M, and 10(-6) M RU486 was not able to completely reverse the CORT effect. In conclusion, along with the regulation of GR, 11 beta-HSD2 may have a key role in glucocorticoid metabolism in L beta T2 cells. MEHP may participate in the glucocorticoid metabolism in L beta T2 cells through inhibition of 11 beta-HSD2 enzyme activity. Such perturbation may be of pathological significance as MEHP may interfere with the reproductive system at pituitary level through regulation of glucocorticoid metabolism, especially in neonates with higher risk of phthalates exposure. (C) 2009 Published by Elsevier Inc.