Chronic growth hormone excess is associated with increased aldosterone: a study in patients with acromegaly and in growth hormone transgenic mice.
Acromegaly is a disease characterized by chronic growth hormone (GH) excess. Since hypertension is a common finding in patients with acromegaly, interactions between GH and the renin-angiotensin-aldosterone system (RAAS) are under controversial debate. We examined GH, IGF-I, aldosterone, and renin in a well-defined group of acromegalic patients before and after cure by surgery. In addition, we analyzed the impact of chronic GH excess on the RAAS in mouse models over-expressing GH alone (G) or in combination with insulin-like growth factor-binding protein-2 (IGFBP-2; GB). Normalization of GH secretion after cure by surgery was accompanied by significant decreases of serum aldosterone in acromegalic patients (pre-op: 96.5 +/- 37.1 pg/mL, post-op: 41.3 +/- 28.2 pg/ mL; P < 0.001; n = 13), but renin concentrations were unaffected. In addition, aldosterone concentrations were positively correlated to GH levels (Spearman r = 0.39; P = 0.025; n = 26). To further study this association, we analysed two transgenic mouse models and found a similar relationship between GH and aldosterone in G mice, which showed about 3-fold elevated serum aldosterone levels in comparison to non-transgenic controls (males: 442 +/- 331 pg/mL vs. 151 +/- 84 pg/mL; P = 0.002; n > or = 12; females: 488 +/- 161 pg/mL vs. 108 +/- 125 pg/mL; P = 0.05; n > or = 4). Expression of aldosterone synthase was similar in adrenal glands of C and G mice. Aldosterone levels in G and GB mice of both genders were not different, indicating that the elevated aldosterone was due to GH excess and not caused by elevated IGF-I, which is known to be blocked by IGFBP-2 overexpression. Also in the mouse models, changes in aldosterone were independent from renin. In summary, we show that chronic GH excess is associated with increased aldosterone in humans and mice. GH-induced increases of aldosterone potentially contribute to the increased cardiovascular risk in acromegalic patients. The underlying mechanism is likely to be independent of renin, excess IGF-I, or adrenal aldosterone synthase expression.
Bielohuby
Maximilian
M
Medizinische Klinik - Innenstadt Klinikum der Universität, Ziemssenstr. 1, 80336 Munich, Germany.
Roemmler
Josefine
J
Manolopoulou
Jenny
J
Johnsen
Inga
I
Sawitzky
Mandy
M
Schopohl
Jochen
J
Reincke
Martin
M
Wolf
Eckhard
E
Hoeflich
Andreas
A
Bidlingmaier
Martin
M
D000172:Acromegaly / Q000097:blood* / Q000601:surgery; D000311:Adrenal Glands / Q000201:enzymology / Q000473:pathology; D000450:Aldosterone / Q000097:blood*; D000818:Animals; D002417:Cattle; D019405:Cytochrome P-450 CYP11B2; D005260:Female; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D009929:Organ Size
D019382:Human Growth Hormone; D000450:Aldosterone; D007334:Insulin-Like Growth Factor I; D019405:Cytochrome P-450 CYP11B2