Hypothalamus/Pituitary/Interrenal Axis in Rainbow Trout: Projecting a Role for the  Melanocortin-5 Receptor Following Interactions with MRAP1 and MRAP2

Presentation Number: MON 372
Date of Presentation: April 3rd, 2017

Alexa L Thomas*1, Robert M Dores1, Perry V Davis1, Erin Faught2 and Mathilakath Vijayan3
1University of Denver, Denver, CO, 2University of Calgary, Calgary, AB, 3University of Calgary, Galgary, AB

Abstract

The obligate interaction between the melanocortin-2 receptor (MC2R) and the accessory protein, MRAP1 on adrenal cortex cells and interrenal cells is essential to promote glucocorticoid synthesis and release to HPA/HPI axes activation in bony fishes, amphibians, reptiles, birds, and mammals is now well established (1). However the role that other melanocortin receptor receptors may play in this process is more obscure. For example mc5R mRNA has been detected in extracts of the adrenal cortex of rodents, but it appears that this receptor is present on zona glomerulosa cells, not zona fasciculata cells (2). In non-mammalian vertebrates that utilize interrenal cells for glucocorticoid synthesis, including the rainbow trout (a modern bony fish; 3) or the Japanese stingray ( a cartilaginous fish; 4) both mc2R and mc5r mRNA has been detected in the interrenal tissue (3,6). With respect to the rainbow trout (rt) interrenal tissue, we have also detected mrap1 and mrap2 mRNA in this tissue. To determine whether there is an interaction between rtMC5R and rtMRAP1 or rtMRAP2, CHO cells were either transiently transfected with rtMC5R + rtMRAP1 or rtMC5R + rtMRAP2 and stimulated with hACTH(1-24). The EC50 value for cells transfected with rtMC5R/rtMRAP1 was nearly 10 fold more sensitive than cells transfected with only rtMC5R. However, the EC50 value for cells transfected with rtMC5R + rtMRAP2 was over 100 fold more sensitive than cells transfected with rtMC5R alone. Interestingly, co-expression of rtMC5R with either rtMRAP1 or rtMRAP2 had no effect, positive or negative, on sensitivity to NDP-MSH. Also, heterodimer formation between either rtMCRAP1/rtMRAP2 or rtMC5R/rtMC2R did not reveal any negative effects on ligand sensitivity. Thus it appears that at least for some non-mammalian vertebrates both MC2R and MC5R may have a role in stress-mediated glucocorticoid biosynthesis. These results for rainbow trout interrenal tissues will be compared to analyses of Japanese stingray interrenal tissue. In addition, the possible role of MC2R and MC5R in glucocorticoid synthesis will be discussed in light of the hypothesis that the mc2r and mc5r genes arose as a result of a local gene duplication event.

 

Nothing to Disclose: ALT, RMD, PVD, EF, MV