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Endocrine Abstracts (2012) 29 S23.2

1University of Mississippi, Jackson, Mississippi, USA; 2G.V. Montgomery VA Medical Center, Jackson, Mississippi, USA.

Aldosterone (aldo) concentrations in the brain and heart are slightly lower, but parallel those in the plasma. Plasma, heart and urine aldosterone continue to be detected in very small amounts in adrenalectomized (ADX) rats, however the concentrations of aldosterone in the brain, though very low, are higher than plasma levels in ADX rats. StAR protein and all of the steroidogenic enzymes necessary for the synthesis of aldosterone are expressed in the central nervous system (CNS) of rats and humans. Brain tissue from ADX rats synthesizes aldo from endogenous substrate and converts 3H-deoxycorticosterone into 3H-aldosterone in vitro. Inappropriately high aldo levels are associated with increased sympathetic drive and hypertension of central origin. Aldo synthesized in the brain appears to play a role in the development of hypertension in the Dahl salt-sensitive rat. Aldo concentration in the hypothalamus of Dahl SS rats is higher than in Sprague-Dawley controls and inhibition of enzymes within the aldosterone biosynthetic pathway, including trilostane, a 3-hydroxysteroid dehydrogenase, and aldosterone synthase, decreases the BP in the Dahl SS rat. Rats in which the aldosterone synthase enzyme cDNA is over-expressed in neurons also have hypertension.

Though most of the aldo in the brain is sequestered from circulating aldo synthesized by the adrenal gland, a small proportion is locally synthesized in the normal rat. As the amount is exceedingly low and number of cells that produce aldo in the brain few, aldo produced in the brain, if relevant, would be expected to have autocrine or paracrine functions. Aldo synthesized in the CNS might have a role in those forms of hypertension and autonomic dysfunction in which circulating aldo is not elevated, but which respond nonetheless to mineralocorticoid receptor antagonists.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details are unavailable.

Volume 29

15th International & 14th European Congress of Endocrinology

European Society of Endocrinology 

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