Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
J Clin Endocrinol Metab. 2021 Apr 23;106(5):1389-1397. doi: 10.1210/clinem/dgab007.
While previous studies indicate that the zonae reticularis (ZR) and glomerulosa (ZG) diminish with aging, little is known about age-related transformations of the zona fasciculata (ZF).
To investigate the morphological and functional changes of the adrenal cortex across adulthood, with emphasis on (i) the understudied ZF and (ii) sexual dimorphisms.
We used immunohistochemistry to evaluate the expression of aldosterone synthase (CYP11B2), visinin-like protein 1 (VSNL1), 3β-hydroxysteroid dehydrogenase type II (HSD3B2), 11β-hydroxylase (CYP11B1), and cytochrome b5 type A (CYB5A) in adrenal glands from 60 adults (30 men), aged 18 to 86. Additionally, we employed mass spectrometry to quantify the morning serum concentrations of cortisol, 11-deoxycortisol (11dF), 17α-hydroxyprogesterone, 11-deoxycorticosterone, corticosterone, and androstenedione in 149 pairs of age- and body mass index-matched men and women, age 21 to 95 years.
The total cortical area was positively correlated with age (r = 0.34, P = 0.008). Both the total (VSNL1-positive) and functional ZG (CYP11B2-positive) areas declined with aging in men (r = -0.57 and -0.67, P < 0.01), but not in women. The CYB5A-positive area declined with age in both sexes (r = -0.76, P < 0.0001). In contrast, the estimated ZF area correlated positively with age in men (r = 0.59, P = 0.0006) and women (r = 0.49, P = 0.007), while CYP11B1-positive area remained unchanged across ages. Serum cortisol, corticosterone, and 11-deoxycorticosterone levels were stable across ages, while 11dF levels increased slightly with age (r = 0.16, P = 0.007).
Unlike the ZG and ZR, the ZF and the total adrenal cortex areas enlarge with aging. An abrupt decline of the ZG occurs with age in men only, possibly contributing to sexual dimorphism in cardiovascular risk.
虽然先前的研究表明，网状带（ZR）和球状带（ZG）随年龄增长而减少，但关于束状带（ZF）与年龄相关的变化知之甚少。
研究成年期肾上腺皮质的形态和功能变化，重点关注（i）研究较少的 ZF 和（ii）性别二态性。
我们使用免疫组织化学方法评估醛固酮合酶（CYP11B2）、类视黄醇蛋白 1（VSNL1）、3β-羟类固醇脱氢酶 2 型（HSD3B2）、11β-羟化酶（CYP11B1）和细胞色素 b5 型 A（CYB5A）在 60 名成年人（30 名男性）肾上腺中的表达，年龄为 18 至 86 岁。此外，我们采用质谱法对 149 对年龄和体重指数匹配的 21 至 95 岁男性和女性的清晨血清皮质醇、11-脱氧皮质醇（11dF）、17α-羟孕酮、11-脱氧皮质酮、皮质酮和雄烯二酮的浓度进行了定量分析。
总皮质面积与年龄呈正相关（r = 0.34，P = 0.008）。男性的总（VSNL1 阳性）和功能性 ZG（CYP11B2 阳性）面积均随年龄增长而下降（r = -0.57 和 -0.67，P <0.01），但女性则不然。CYB5A 阳性面积在两性中均随年龄增长而下降（r = -0.76，P <0.0001）。相比之下，男性（r = 0.59，P = 0.0006）和女性（r = 0.49，P = 0.007）的估计 ZF 面积与年龄呈正相关，而 CYP11B1 阳性面积在整个年龄段保持不变。血清皮质醇、皮质酮和 11-脱氧皮质酮水平在整个年龄段保持稳定，而 11dF 水平随年龄略有增加（r = 0.16，P = 0.007）。
与 ZG 和 ZR 不同，ZF 和整个肾上腺皮质面积随年龄增长而增大。只有男性的 ZG 随年龄急剧下降，这可能导致心血管风险的性别二态性。
