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Abstract

Mono-(2-ethylhexyl) phthalate (MEHP) regulates glucocorticoid metabolism through 11ß-hydroxysteroid dehydrogenase 2 in murine gonadotrope cells 
Hong,Dun; Li,Xing-Wang; Lian,Qing-Quan; Lamba,Pankaj; Bernard,Daniel J.; Hardy,Dianne O.; Chen,Hai-Xiao; Ge,Renshan
Biochemical and Biophysical Research Communication 389(2): 305-309
Publication date: 2009


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 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2), not 11ß-HSD1, is strongly expressed in murine gonadotrope LßT2 cells. Interestingly, MEHP inhibited Hsd11b2 mRNA level and 11ß-HSD2 enzyme activity in LßT2 cells at as low as 10 M. Corticosterone (CORT) at a concentration of 10 M significantly inhibited LßT2 cell proliferation after 2-day culture, and 10 M RU486, an antagonist of glucocorticoid receptor (GR), reversed this inhibition. However, in the presence of 10 or 10 M MEHP, the minimal concentration of CORT to inhibit the proliferation of LßT2 cells was lowered to 10 M, and 10 M RU486 was not able to completely reverse the CORT effect. In conclusion, along with the regulation of GR, 11ß-HSD2 may have a key role in glucocorticoid metabolism in LßT2 cells. MEHP may participate in the glucocorticoid metabolism in LßT2 cells through inhibition of 11ß-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.