(T1230-05-33) Renal Monocarboxylate Transporter Expression in Response to Female Sex and Cross-Sex Hormone Treatment

Purpose: The kidney plays an important role in maintaining body homeostasis through filtration, reabsorption, secretion and urinary excretion of endogenous and exogenous compounds. Monocarboxylate transporters are one of the membrane transporter families that participate in renal tubule function. Both proton (MCT) and sodium (SMCT) dependent monocarboxylate transporters are expressed in the proximal renal tubules. Monocarboxylate transporters are involved in reabsorption of short chain fatty acids, ketone bodies and monocarboxylate drugs. Our lab previously demonstrated the hepatic and renal MCTs/SMCTs varied between the sexes, over the estrous cycle, in the absence of male and female sex hormone, which indicated that MCT/SMCT expression can be altered by changes in sex hormone level. However, there is a lack of data on renal MCTs/SMCT expression in response to exogenous female sex hormones in the cis- and trans-gender population. Therefore, the objective of current study is to investigate sex and cross-sex hormone-dependent regulation of renal MCTs and SMCTs.

Methods: MCT1, MCT4, CD147 and SMCT1expression were evaluated in male, female, ovariectomized (OVX) females and castrated (CST) male Sprague-Dawley rats treated. OVX or CST surgery was performed at 8 weeks of age. At 10 weeks of age, OVX females and CST males were treated with 60-day release pellets of 17β-estradiol (1.5 mg) and/or progesterone (50 mg) or corresponding placebo for 21 days (N = 5 – 6 per group) when kidney samples were collected. Membrane bound protein samples were isolated from kidney tissues and western blot was performed to evaluate transporter membrane protein expression.

Results: CST estrogen showed significantly lower MCT1 membrane expression than intact males. MCT1 membrane expression of OVX combo was significantly lower than OVX combo placebo. MCT4 has significantly higher membrane expression in intact males when compared to OVX estrogen placebo, CST estrogen, OVX progesterone, CST progesterone placebo/progesterone and CST combo. CST progesterone also showed significantly lower MCT4 membrane expression than females. CST combo also varied significantly lower than CST combo placebo. Similar to MCT1 and MCT4, CD147 membrane expression in CST estrogen was significantly lower than intact males. SMCT1 membrane expression was significantly lower in OVX estrogen placebo, CST estrogen placebo, OVX progesterone placebo /progesterone, CST progesterone placebo/progesterone, when compared to intact females had significantly higher CST estrogen and CST combo showed significantly higher SMCT1 membrane expression when compared to their corresponding controls.

Conclusion: Our results demonstrate that MCT1, MCT4, CD147 and SMCT1 renal expression are significantly altered in response to female sex hormones in both OVX and CST rats, which may indicate the same effect on corresponding cis-gender and trans-gender populations. The mechanisms underlying MCT/SMT regulation by female sex hormones appear to vary based on the specific transporter. Future studies will investigate the role of sex hormone receptors in MCT/SMCT regulation.

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Acknowledgements: Funding for this project was provided by NIDA/NIGMS DA052120.