Adrenals

Abstract

This year we have moved from Reproductive Endocrinology to the Adrenals. As always, we have tried to focus on papers that are clinically relevant or at least herald concepts and mechanisms that might be relevant to pediatric endocrinology in the future. As is often the case, pediatric research -especially in the field of therapeutics -tends to lag behind adult medicine. However, increasing evidence suggests that many aspects of adrenal function can be programmed in early life and many 'longterm' consequences of adrenal disease have their roots in childhood or adolescence. Therefore, we are in a prime position to try to relate new concepts and mechanisms to the pediatric population with potentially long-term benefits for individual and population health. Mechanisms of the year: a new task for the adrenall TASK channel deletion in mice causes primary hyperaldosteronismDavies LA, Hu C, Guagliardo NA, Sen N, Chen X, Talley EM, Carey RM, Bayliss DA, Barrett PQ Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, Va., USA Proc Natl Acad Sci USA 2008;105:2203-2208 Background: Inappropriate, autonomous overproduction of aldosterone from the adrenal gland is the most frequent cause of secondary hypertension. However, the etiology of most forms of bilateral idiopathic hyperaldosteronism is unknown. TWIK-related acid-sensitive K (TASK)-1 or TASK-3 channels may play an important role in regulating potassium currents and polarization of the zona glomerulosa cell membrane. Modulation of this system may affect aldosterone release. Methods: TASK-1-and TASK-3-deleted mice were generated and adrenal function was studied. Results: Although TASK channel-deleted mice (TASKϪրϪ) were able to adjust urinary sodium excretion and aldosterone production to match sodium intake, these animals produced more aldosterone than control mice across the whole range of Na intake. Aldosterone overproduction was largely independent of renin-angiotensin activity, as renin levels were normal or lower in knockout animals. In addition, TASKϪրϪ deleted mice failed to suppress aldosterone production in response to dietary Na loading and did not normalize aldosterone following candesartan blockade of the angiotensin type 1 receptor. Conclusion(s): TASKϪրϪ channel knockout mice exhibit a phenotype of primary hyperaldosteronism and represent a novel animal model of nontumorigenic primary hyperaldosteronism. Consequently, TASK channels are potential therapeutic targets for treating primary hyperaldosteronism and for preventing hyperaldosterone-related cardiac and renal damage in the future.Our traditional view of the hypothalamic-pituitary-adrenal (HPA) axis is of a hierarchical system with integrated feedback loops at different levels. However, it is emerging that local factors such as paracrine influences and ultrashort feedback loops may be important in establishing the 'set point' for responsiveness at the different levels of the axis. It is likely that other mechanisms exist that make the adrenal more or less likely to r...

Adrenals

“…Indeed, the mouse model reported by Benigni et al shows that disruption of the angiotensin 1A receptor in mice results in quite markedly increased longevity. This is in line with a mouse model of a gain-of-function mutation of AT 1 showing progressive cardiac fibrosis with increased expression of collagen. These studies offer a rationale for exploring the possibility that AT 1 antagonists will prolong life in humans.…”

“…Whenever possible we have avoided subjects which have been discussed in detail in the Yearbook 2008, unless progress in the field has been incremental [1]. Some emerging themes include modulators of steroidogenesis as a cause of variant phenotypes or new monogenic disorders; peripheral circadian regulation within the adrenal itself; DHEA and adrenarche; and potential cancer therapies developed from studying the molecular pathophysiology of adrenal tumor tissues and cells.…”