Sex Hormone-Dependent Regulation of Rat Hepatic Monocarboxylate Transporters Expression
Poster Number
41
Introduction/Abstract
Proton-dependent monocarboxylate transporters (MCTs) are involved in monocarboxylate uptake and efflux in a range of biologically important tissues and barriers, including the liver, kidney, and blood-brain barrier (BBB) (1). MCTs are involved in the transport of L-lactate and monocarboxylate drugs, including gamma-hydroxybutyrate, valproic acid, gabapentin enacarbil, non-steroidal anti-inflammatories, and β-lactam antibiotics (1). In our laboratory, we have published data demonstrating sex hormone-dependent regulation of hepatic MCT1, MCT4, and CD147 in intact male and female rats (3). These data support sex hormone-dependent regulation of the underlying physiological processes governing the distribution and clearance of MCT substrates.
Purpose
The purpose of this project is to quantify hepatic MCT1, MCT4, and CD147 membrane protein expression in rats treated with sex and cross-sex hormone therapy.
Method
Male and female Sprague Dawley (SD) rats, ovariectomized (OVX) females and castrated (CST) males were obtained from Charles River at 8 weeks of age and were housed in a temperature-controlled room with a 12-hour day/night lighting cycle. At 10 weeks of age, OVX female and CST male SD rats were implanted subcutaneously with 60-day release pellets containing 1.5 mg estrogen and/or 50 mg progesterone or 7.5mg testosterone or their corresponding control pellets (Innovative Research of America) (N = 6/treatment group). Following euthanasia, livers were harvested. Membrane-bound protein was extracted from the liver using a ProteoExtract Native Membrane Extraction kit. Na+/K+ ATPase expression was evaluated by western blot to verify membrane isolation. MCT1, MCT4, and CD147 protein expression levels were quantified by western blot and normalized to total lane expression.
Significance
Results from this project will advance our fundamental knowledge of sex hormone regulation of drug transporters. Understanding the gender-specific drug transporter variation is particularly important for designing safe and effective treatments. Characterization of these regulatory pathways has broad-based application in other clinical research areas where monocarboxylate transporters have been identified as putative therapeutic targets.
Location
Library and Learning Center, 3601 Pacific Ave., Stockton, CA 95211
Format
Poster Presentation
Sex Hormone-Dependent Regulation of Rat Hepatic Monocarboxylate Transporters Expression
Library and Learning Center, 3601 Pacific Ave., Stockton, CA 95211
Proton-dependent monocarboxylate transporters (MCTs) are involved in monocarboxylate uptake and efflux in a range of biologically important tissues and barriers, including the liver, kidney, and blood-brain barrier (BBB) (1). MCTs are involved in the transport of L-lactate and monocarboxylate drugs, including gamma-hydroxybutyrate, valproic acid, gabapentin enacarbil, non-steroidal anti-inflammatories, and β-lactam antibiotics (1). In our laboratory, we have published data demonstrating sex hormone-dependent regulation of hepatic MCT1, MCT4, and CD147 in intact male and female rats (3). These data support sex hormone-dependent regulation of the underlying physiological processes governing the distribution and clearance of MCT substrates.
