Pomc knockout mice have secondary hyperaldosteronism despite an absence of adrenocorticotropin.
Aldosterone production is controlled by angiotensin II, potassium, and ACTH. Mice lacking Pomc and its pituitary product ACTH have been reported to have absent or low aldosterone levels, suggesting that ACTH is required for normal aldosterone production. However, this is at odds with the clinical finding that human aldosterone deficiency is not a component of secondary adrenal insufficiency. To resolve this, we measured plasma and urine electrolytes, together with plasma aldosterone and renin activity, in Pomc(-/-) mice. We found that these mice have secondary hyperaldosteronism (elevated aldosterone without suppression of renin activity), indicating that ACTH is not required for aldosterone production or release in vivo. Exogenous ACTH stimulates a further increase in aldosterone in Pomc(-/-) mice, whereas angiotensin II has no effect, and the combination of angiotensin II and ACTH is no more potent than ACTH alone. These data suggest that aldosterone production and release in vivo do not require the action of ACTH during development or postnatal life and that secondary hyperaldosteronism in Pomc(-/-) mice is a consequence of glucocorticoid deficiency.
Linhart
Kirsten-Berit
KB
Division of Endocrinology, Children's Hospital, Boston, MA 02115, USA.
Majzoub
Joseph A
JA
D000309:Adrenal Insufficiency / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D000324:Adrenocorticotropic Hormone / Q000172:deficiency* / Q000378:metabolism / Q000494:pharmacology; D000450:Aldosterone / Q000097:blood*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D005260:Female; D006929:Hyperaldosteronism / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011188:Potassium / Q000097:blood / Q000652:urine; D011333:Pro-Opiomelanocortin / Q000235:genetics* / Q000378:metabolism; D012083:Renin / Q000097:blood; D012964:Sodium / Q000097:blood / Q000652:urine; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D000450:Aldosterone; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D012964:Sodium; D012083:Renin; D011188:Potassium