Abstract
It is unknown whether and how osmoregulation is controlled by corticosteroid signaling in the phylogenetically basal vertebrate group Agnatha, including lampreys and hagfishes. It is known that a truncated steroid biosynthetic pathway in lampreys produces two predominant circulating corticosteroids, 11-deoxycortisol (S) and 11-deoxycorticosterone (DOC). Furthermore, lampreys express only a single, ancestral corticosteroid receptor (CR). Whether S and/or DOC interact with the CR to control osmoregulation in lampreys is still unknown. We examined the role of the endogenous corticosteroids in vivo and ex vivo in sea lamprey (Petromyzon marinus) during the critical metamorphic period during which sea lamprey increase osmoregulatory capacity and acquire seawater (SW) tolerance. We demonstrate in vivo that increases in circulating [S] and gill CR abundance are associated with increases in osmoregulatory capacity during metamorphosis. We further show that in vivo and ex vivo treatment with S increases activity and expression of gill active ion transporters and improves SW tolerance, and that only S (and not DOC) has regulatory control over active ion transport in the gills. Lastly, we show that the lamprey CR expresses an ancestral, spironolactone-as-agonist structural motif and that spironolactone treatment in vivo increases osmoregulatory capacity. Together, these results demonstrate that S is an osmoregulatory hormone in lamprey and that receptor-mediated discriminative corticosteroid regulation of hydromineral balance is an evolutionarily basal trait among vertebrates.
Highlights
It is unknown whether and how osmoregulation is controlled by corticosteroid signaling in the phylogenetically basal vertebrate group Agnatha, including lampreys and hagfishes
This work provides several novel lines of evidence that S is the primary corticosteroid hormone that acts through the ancestral corticosteroid receptor (CR) to control osmoregulation in the basal vertebrate, sea lamprey: (i) plasma [S] and gill CR abundance are upregulated during metamorphosis when endogenous increases in salinity tolerance occur; (ii) plasma [S] is upregulated during SW exposure; (iii) ex vivo and in vivo treatment with S upregulates expression of critical active gill ion transporters and increases SW tolerance; (iv) in vivo treatment with the other known circulating corticosteroid in lamprey, DOC, does not upregulate such transcellular ionoregulatory machinery; and (v) treatment with a pharmacological agonist of the lamprey CR, spironolactone, is effective in stimulating lamprey gill ion transporter activity similar to the effects of S
To understand how corticosteroids control osmoregulation in lamprey, it is necessary to observe the nature of endogenous osmoregulatory and endocrine changes that occur naturally during metamorphosis and SW acclimation
Summary
It is unknown whether and how osmoregulation is controlled by corticosteroid signaling in the phylogenetically basal vertebrate group Agnatha, including lampreys and hagfishes. One approach using classical ex vivo receptor binding studies demonstrated that the lamprey CR only had affinity for S 1, yet a different approach expressing the ligand binding domain of the lamprey CR in mammalian cells in vitro demonstrated the lamprey CR can be activated by several corticosteroids including both endogenous terminal corticosteroids in lamprey, S and DOC2 This raises the question of whether S or DOC or both act as a hormone in the basal vertebrate group, and there is a need to better understand the true physiological role of the lamprey CR and its interaction with the endogenous corticosteroids, S and DOC. There is a clear need for more in vivo studies to discern the true physiological role of corticosteroid signaling in controlling hydromineral balance in this basal vertebrate group
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