Meeting Abstract

P2-17   -   Glucocorticoid receptor signaling controls modulators of salt-water homeostasis in Xenopus tropicalis tadpoles Paul, B*; Buchholz, DR; Department of Biological Sciences, University of Cincinnati, Cincinnati, Ohio, USA; Department of Biological Sciences, University of Cincinnati, Cincinnati, Ohio, USA paulbi@mail.uc.edu https://www.linkedin.com/in/bidishapaul/

Hyperactivity of the HPA axis due to lack of glucocorticoid receptor (GR) signaling significantly alters modulators of salt-water homeostasis which promotes pathogenesis of chronic kidney disease and cardiovascular diseases. We characterized HPA hyperactivity in glucocorticoid receptor knockout (GRKO) tadpoles. GRKO tadpoles have high mRNA expression of genes stimulating HPA activity such as pomc, star, cyp21a2, cyp17a1 and cyp11b2 along with high plasma levels of corticosterone (CORT) and aldosterone (ALDO). We also found high mRNA expression of the mineralocorticoid receptor (MR) in brain, kidney and skin in the GRKO tadpoles. ALDO is a key hormone increasing water absorption in humans and subsequently increasing blood volume and blood pressure, such that treatment of tadpoles with ALDO for 24 hrs leads to elevated water weight. However, despite high endogenous ALDO levels in GRKO tadpoles, water weight in GRKO tadpoles was no different than wild type siblings. As potential compensatory mechanisms, we found that GRKO tadpoles have lower mRNA expression levels of arginine-vasotocin (AVT), which helps in water absorption, and high levels of progesterone, which causes loss of salt and water in tadpoles. Altered levels of AVT and progesterone in GRKO tadpoles might counteract the stimulating effect of high ALDO on water absorption. Thus, GRKO tadpoles can maintain appropriate water content despite high ALDO levels indicates the presence of compensatory mechanisms within HPA axis among vertebrates. However, total water weight does not represent absolute quantification of salt-water homeostasis and does not rule out kidney and heart damage due to high MR and ALDO levels. Hence future studies should focus on examining tissue and/or cell specific effects of ALDO, AVT and progesterone on salt retention.