Effects of Methamphetamine on the Expression of Sulfotransferases in Endocrine Glands and the Liver of Rats

Abstract

My objectives were to: 1) To investigate the effects of METH on protein expression of different SULT isoforms in the adrenal gland, the thyroid gland, and the ovary/testis of rats. 2) To investigate the effects of METH on mRNA transcriptions of different SULT isoforms in the adrenal gland, the thyroid gland, and the ovary/testis of rats. 3) To investigate the effects of METH on protein expression and mRNA transcription of SULTs in the liver of rats. Male and Female Sprague–Dawley rats (Harlan, Indianapolis, IN), 10 to 11 weeks old and 200 to 300 g body weight were used in this investigation. Rats were housed in a temperature– and humidity–controlled room and supplied with rodent chow and water for at least 1 week before use. Rats were divided randomly into groups of four. Methamphetamine was dissolved in saline and administrated by intraperitoneal injection at 1, 5 and 20 mg/kg to 3 separate groups of rats. The control rats received only the saline vehicle. The treatment was single dose treatment. The rats were euthanized 24 h after the drug treatment. The livers, the thyroid gland, the adrenal glands, and the testes/ovaries were collected from each rat and were snap–frozen in liquid nitrogen. Samples were stored at minus 80 degree centigrade until use. We found that METH significantly induced the expressions of the rat cholesterol sulfotransferase (rSULT2B1b) in the thyroid gland and the adrenal gland of both female and male rats. This suggests that rSULT2B1b may play a role in the increase of thyroid and adrenal hormone productions after METH exposure through the Liver X Receptor (LXR) regulating pathway, because rSULT2B1b is strongly related to the activation and deactivation of LXRs. I also found that METH significantly induced the expression of rSULT2B1b in the ovary and the expression of the rat pregnenolone sulfotransferase (rSLUT2B1a) in the testis of rats. This suggests that rSULT2B1b and rSULT2B1a may be involved in the expression change of estrogens and testosterone in the ovary and testis of rats caused by METH treatment. Sex–dependent sex hormone levels may serve as one of the reasons for the different METH–induced neurotoxicity in female and male individuals.