The Age-Dependent Changes of the Human Adrenal Cortical Zones Are Not Congruent

Abstract

Background: 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).

Objectives: To investigate the morphological and functional changes of the adrenal cortex across adulthood, with emphasis on (i) the understudied ZF and (ii) sexual dimorphisms.

Methods: 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.

Results: 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).

Conclusion: 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.

Keywords: adrenal; adrenal cortex; aging; zona fasciculata; zona glomerulosa; zona reticularis.

Figure 1.

Representative adrenal images from young and old individuals. Adrenal images of an 18-year-old man (A-F) and a 61-year-old man (G-L), respectively are shown: hematoxylin and eosin staining (H&E, A and F), and immunohistochemistry staining for aldosterone synthase (CYP11B2, B and H); visinin-like 1 (VSNL1, C and I); 3β-hydroxysteroid dehydrogenase type II (HSD3B2, D and J); 11β-hydroxylase (CYP11B1, E and K); and cytochrome b₅ type A (CYB5A, F and L). Scale bars indicate 200 μm.

Figure 2.

Morning serum steroid concentrations across ages. Associations between morning serum steroid concentrations and age are shown in 248 patients: 149 of each sex, matched by age and body mass index. Closed circles represent men and open circles represent women. r represents the Pearson correlation coefficient. Abbreviations: 11dF, 11-deoxycortisol; 17OHP4, 17α-hydroxyprogesterone; A4, androstenedione; DOC, 11-deoxycorticosterone.