Mineralocorticoid Resistance

David S. Geller

Disclosures

Clin Endocrinol. 2005;62(5):513-520. 

In This Article

Mineralocorticoid Resistance: Role of SGK1?

As the above examples show, mineralocorticoid resistance can be caused by the loss of function of any gene product involved in the MR effector pathway. Work in recent years has identified the serum- and glucocorticoid-regulated kinase (sgk1) as a gene activated by aldosterone that, in turn, may upregulate heterologously expressed epithelial sodium channels.[50] To investigate the potential role of sgk1 mutations in mediating mineralocorticoid resistance, Wulff et al . generated a mouse genetically deficient in sgk1.[51] Although a variety of preliminary studies suggested an important role of SGK1 in aldosterone action, mice deficient in SGK1 are able to maintain normal sodium homeostasis on a standard NaCl intake. However, they are unable to appropriately decrease urinary sodium excretion in response to a low-salt diet and similarly demonstrate a defect in renal potassium excretion. These data confirm that sgk1 plays a role in the aldosterone signalling pathway. However, in contrast to the necessary roles of the MR and ENaC in aldosterone function, sgk1 appears to play only a modulatory role necessary for fine-tuning of salt and potassium homeostasis, at least in mice. Importantly, this implies that there are other crucial regulatory pathways in the aldosterone signalling cascade that remain to be described, each of which could provide a useful pharmaceutical target.

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