Yuta Tezuka1,2, Nanako Atsumi1,3, Amy R Blinder4, Juilee Rege4, Thomas J Giordano5, William E Rainey1,4, Adina F Turcu1. 1. Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA. 2. Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. 3. Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. 4. Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA. 5. Department of Pathology and Clinical Laboratories, University of Michigan, Ann Arbor, MI, USA.
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.
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.
Authors: Tsjitske J Toering; Christina M Gant; Folkert W Visser; Anne Marijn van der Graaf; Gozewijn D Laverman; A H Jan Danser; Marijke M Faas; Gerjan Navis; A Titia Lely Journal: Am J Physiol Renal Physiol Date: 2017-06-07
Authors: I J Heuser; U Gotthardt; U Schweiger; J Schmider; C H Lammers; M Dettling; F Holsboer Journal: Neurobiol Aging Date: 1994 Mar-Apr Impact factor: 4.673
Authors: Na Sun; Yin Wu; Kazutaka Nanba; Silviu Sbiera; Stefan Kircher; Thomas Kunzke; Michaela Aichler; Sabina Berezowska; Joachim Reibetanz; William E Rainey; Martin Fassnacht; Axel Walch; Matthias Kroiss Journal: Endocrinology Date: 2018-03-01 Impact factor: 4.736
Authors: Yuta Tezuka; Nanako Atsumi; Amy R Blinder; Juilee Rege; Thomas J Giordano; William E Rainey; Adina F Turcu Journal: J Clin Endocrinol Metab Date: 2021-04-23 Impact factor: 5.958
Authors: Yuta Tezuka; Nanako Atsumi; Amy R Blinder; Juilee Rege; Thomas J Giordano; William E Rainey; Adina F Turcu Journal: J Clin Endocrinol Metab Date: 2021-04-23 Impact factor: 5.958
Authors: Jessica E Baker; Samuel W Plaska; Zhaoping Qin; Chia-Jen Liu; Juilee Rege; William E Rainey; Aaron M Udager Journal: Mol Cell Endocrinol Date: 2021-04-26 Impact factor: 4.369