MON-LB006 Glucocorticoid Biosynthetic Pathway Analysis Divulges the Susceptibility of Adrenal Gland against EDCs In Vivo by Novel Approach Uncovering Endocrine Disruption Mechanism

The adrenal gland is a less focused endocrine organ for the endocrine disrupting effect of endocrine disrupting chemicals (EDCs) leading to the neglected study of glucocorticoid biosynthetic pathway as the target of EDCs. The effects of two extensively used phthalate esters viz. di-ethyl hexyl phthalate (DEHP) and di-butyl phthalate (DBP) on adrenal gland were observed in Wistar rats in the present study to check the susceptibility of the adrenal gland and glucocorticoid biosynthetic pathway against the exposure of these extensively used plasticizers which are well-known EDCs. Wistar rats were divided into seven groups (n = 5) and received the treatment for fourteen days. Group I was the control group and received only corn oil which is used as a vehicle. Group II, III and IV received a daily dose of DEHP of 250 mg/kg-BW, 750 mg/kg-BW and 1500 mg/kg-BW respectively while group V, VI and VII received a daily dose of DBP of 100 mg/kg-BW, 500 mg/kg-BW and 1000 mg/kg-BW respectively. The comparative microscopic study of histological slides of endocrine glands i.e. pituitary, pineal, thyroid, parathyroid, adrenal gland and testes revealed the susceptibility of adrenal gland towards the DEHP and DBP. Glucocorticoid biosynthetic pathway was analyzed by molecular docking study of DEHP and DBP with the enzyme proteins of the pathway using Maestro Schrodinger 9.4 software showing the potential of DEHP and DBP to inhibit these proteins comparable to the known inhibitors of these enzymes. The expression study of enzymes of this pathway i.e. StAR, 3β-HSD, CYP21A1, CYP1B1 and CYP11B2 on exposure to DEHP and DBP by real-time PCR has also assessed the sensitivity of the pathway. However, the 2D-nano-LC-MS-MS data of adrenal gland tissue is yet to come which will display the differential expression of proteins and will clear the picture of the glucocorticoid biosynthetic pathway as a potential target of EDCs and will elucidate the novel approach of the mechanism of endocrine disruption. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.