Skip to main content

Advertisement

SpringerLink
Log in

Female baboon adrenal zona fasciculata and zona reticularis regulatory and functional proteins decrease across the life course

  • ORIGINAL ARTICLE
  • Published:
GeroScience Aims and scope Submit manuscript

Abstract

Debate exists on life-course adrenocortical zonal function trajectories. Rapid, phasic blood steroid concentration changes, such as circadian rhythms and acute stress responses, complicate quantification. To avoid pitfalls and account for life-stage changes in adrenocortical activity indices, we quantified zonae fasciculata (ZF) and reticularis (ZR) across the life-course, by immunohistochemistry of key regulatory and functional proteins. In 28 female baboon adrenals (7.5–22.1 years), we quantified 12 key proteins involved in cell metabolism, division, proliferation, steroidogenesis (including steroid acute regulatory protein, StAR), oxidative stress, and glucocorticoid and mitochondrial function. Life-course abundance of ten ZF proteins decreased with age. Cell cycle inhibitor and oxidative stress markers increased. Seven of the 12 proteins changed in the same direction for ZR and ZF. Importantly, ZF StAR decreased, while ZR StAR was unchanged. Findings indicate ZF function decreased, and less markedly ZR function, with age. Causes and aging consequences of these changes remain to be determined.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data Availability

The data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request. Data are located in controlled access data storage at Texas Biomedical Research Institute.

References

  1. Clegg A, Hassan-Smith Z. Frailty and the endocrine system. Lancet Diabetes Endocrinol. 2018;6(9):743–52. https://doi.org/10.1016/S2213-8587(18)30110-4.

    Article  CAS  PubMed  Google Scholar 

  2. Adekunbi DA, Li C, Nathanielsz PW, Salmon AB. Age and sex modify cellular proliferation responses to oxidative stress and glucocorticoid challenges in baboon cells. Geroscience. 2021. https://doi.org/10.1007/s11357-021-00395-1.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Zambrano E, Reyes-Castro LA, Nathanielsz PW. Aging, glucocorticoids and developmental programming. Age (Dordrecht, Netherlands). 2015;37(3):9774. https://doi.org/10.1007/s11357-015-9774-0.

    Article  CAS  PubMed  Google Scholar 

  4. Honnebier MB, Jenkins SL, Nathanielsz PW. Circadian timekeeping during pregnancy: endogenous phase relationships between maternal plasma hormones and the maternal body temperature rhythm in pregnant rhesus monkeys. Endocrinology. 1992;131(5):2051–8. https://doi.org/10.1210/endo.131.5.1330486.

    Article  CAS  PubMed  Google Scholar 

  5. Nathanielsz PW, Huber HF, Li C, Clarke GD, Kuo AH, Zambrano E. The nonhuman primate hypothalamo-pituitary-adrenal axis is an orchestrator of programming-aging interactions: role of nutrition. Nutr Rev. 2020;78(Supplement 2):48–61. https://doi.org/10.1093/nutrit/nuaa018.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Magyar DM, et al. Time-trend analysis of plasma cortisol concentrations in the fetal sheep in relation to parturition. Endocrinology. 1980;107(1):155–9. https://doi.org/10.1210/endo-107-1-155.

    Article  CAS  PubMed  Google Scholar 

  7. Downs JL, Mattison JA, Ingram DK, Urbanski HF. Effect of age and caloric restriction on circadian adrenal steroid rhythms in rhesus macaques. Neurobiol Aging. 2008;29(9):1412–22. https://doi.org/10.1016/j.neurobiolaging.2007.03.011.

    Article  CAS  PubMed  Google Scholar 

  8. Zambrano E, et al. Developmental programming-aging interactions have sex-specific and developmental stage of exposure outcomes on life course circulating corticosterone and dehydroepiandrosterone (DHEA) concentrations in rats exposed to maternal protein-restricted diets. Nutrients. 2023;15(5):1239. https://doi.org/10.3390/nu15051239.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Yang S, et al. A decline in female baboon hypothalamo-pituitary-adrenal axis activity anticipates aging. Aging (Albany NY). 2017;9(5):1375–85. https://doi.org/10.18632/aging.101235.

    Article  CAS  PubMed  Google Scholar 

  10. Willis EL, Wolf RF, White GL, McFarlane D. Age- and gender-associated changes in the concentrations of serum TGF-1β, DHEA-S and IGF-1 in healthy captive baboons (Papio hamadryas anubis). Gen Comp Endocrinol. 2014;195:21–7. https://doi.org/10.1016/j.ygcen.2013.10.004.

    Article  CAS  PubMed  Google Scholar 

  11. Willis EL, Eberle R, Wolf RF, White GL, McFarlane D. The effects of age and cytomegalovirus on markers of inflammation and lymphocyte populations in captive baboons. PLoS ONE. 2014;9(9):e107167. https://doi.org/10.1371/journal.pone.0107167.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Cox LA, et al. Baboons as a model to study genetics and epigenetics of human disease. ILAR J. 2013;54(2):106–21. https://doi.org/10.1093/ilar/ilt038.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Choi J, Li C, McDonald TJ, Comuzzie A, Mattern V, Nathanielsz PW. Emergence of insulin resistance in juvenile baboon offspring of mothers exposed to moderate maternal nutrient reduction. Am J Physiol Regul Integr Comp Physiol. 2011;301(3):R757–62. https://doi.org/10.1152/ajpregu.00051.2011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Huber HF, Nathanielsz PW, Clarke GD. Summary and assessment of studies on cardiac aging in nonhuman primates. Comp Med. 2021;71(6):460–5. https://doi.org/10.30802/AALAS-CM-21-000038.

    Article  CAS  PubMed  Google Scholar 

  15. Kuo AH, Li C, Li J, Huber HF, Nathanielsz PW, Clarke GD. Cardiac remodelling in a baboon model of intrauterine growth restriction mimics accelerated ageing. J Physiol (Lond). 2017;595(4):1093–110. https://doi.org/10.1113/JP272908.

    Article  CAS  PubMed  Google Scholar 

  16. Bronikowski AM, Alberts SC, Altmann J, Packer C, Carey KD, Tatar M. The aging baboon: comparative demography in a non-human primate. PNAS. 2002;99(14):9591–5. https://doi.org/10.1073/pnas.142675599.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Grieves JL, et al. Barbiturate euthanasia solution-induced tissue artifact in nonhuman primates. J Med Primatol. 2008;37(3):154–61. https://doi.org/10.1111/j.1600-0684.2007.00271.x.

    Article  CAS  PubMed  Google Scholar 

  18. Saxton RA, Sabatini DM. mTOR signaling in growth, metabolism, and disease. Cell. 2017;168(6):960–76. https://doi.org/10.1016/j.cell.2017.02.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hu Q, Huang T. Regulation of the cell cycle by ncRNAs affects the efficiency of CDK4/6 inhibition. Int J Mol Sci. 2023;24(10):8939. https://doi.org/10.3390/ijms24108939.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Juríková M, Danihel Ľ, Polák Š, Varga I. Ki67, PCNA, and MCM proteins: markers of proliferation in the diagnosis of breast cancer. Acta Histochem. 2016;118(5):544–52. https://doi.org/10.1016/j.acthis.2016.05.002.

    Article  CAS  PubMed  Google Scholar 

  21. Galano M, Venugopal S, Papadopoulos V. Role of STAR and SCP2/SCPx in the transport of cholesterol and other lipids. Int J Mol Sci. 2022;23(20):12115. https://doi.org/10.3390/ijms232012115.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Auchus RJ. Overview of dehydroepiandrosterone biosynthesis. Semin Reprod Med. 2004;22(4):281–8. https://doi.org/10.1055/s-2004-861545.

    Article  CAS  PubMed  Google Scholar 

  23. Fadel L, et al. Modulating glucocorticoid receptor actions in physiology and pathology: insights from coregulators. Pharmacol Ther. 2023;251:108531. https://doi.org/10.1016/j.pharmthera.2023.108531.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Brand MD, Orr AL, Perevoshchikova IV, Quinlan CL. The role of mitochondrial function and cellular bioenergetics in ageing and disease. Br J Dermatol. 2013;169 Suppl 2(0 2):1–8. https://doi.org/10.1111/bjd.12208.

    Article  CAS  PubMed  Google Scholar 

  25. Zhou S, Yu Q, Zhang L, Jiang Z. Cyclophilin D-mediated mitochondrial permeability transition regulates mitochondrial function. Curr Pharm Des. 2023;29(8):620–9. https://doi.org/10.2174/1381612829666230313111314.

    Article  CAS  PubMed  Google Scholar 

  26. Shahab M, Jamesdaniel S. Nitrative stress and auditory dysfunction. Pharmaceuticals (Basel). 2022;15(6):649. https://doi.org/10.3390/ph15060649.

    Article  CAS  PubMed  Google Scholar 

  27. Li C, et al. Effects of maternal global nutrient restriction on fetal baboon hepatic insulin-like growth factor system genes and gene products. Endocrinology. 2009;150(10):4634–42. https://doi.org/10.1210/en.2008-1648.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Li C, et al. Up-regulation of the fetal baboon hypothalamo-pituitary-adrenal axis in intrauterine growth restriction: coincidence with hypothalamic glucocorticoid receptor insensitivity and leptin receptor down-regulation. Endocrinology. 2013;154(7):2365–73. https://doi.org/10.1210/en.2012-2111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Dodds RM, et al. Grip strength across the life course: normative data from twelve British studies. PLoS ONE. 2014;9(12):e113637. https://doi.org/10.1371/journal.pone.0113637.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Coelho AM. Baboon dimorphism: growth in weight, length and adiposity from birth to 8 years of age. In: Watts ES, editor. Nonhuman primate models for human growth and development. New York: Alan R. Liss; 1985. p. 125–59.

    Google Scholar 

  31. Sharma M, et al. Circadian rhythms of melatonin and cortisol in aging. Biol Psychiatry. 1989;25(3):305–19. https://doi.org/10.1016/0006-3223(89)90178-9.

    Article  CAS  PubMed  Google Scholar 

  32. Masoro EJ. Glucocorticoids and aging. Aging (Milano). 1995;7(6):407–13. https://doi.org/10.1007/BF03324354.

    Article  CAS  PubMed  Google Scholar 

  33. Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 2009;9(3):153–66. https://doi.org/10.1038/nrc2602.

    Article  CAS  PubMed  Google Scholar 

  34. Shivji KK, Kenny MK, Wood RD. Proliferating cell nuclear antigen is required for DNA excision repair. Cell. 1992;69(2):367–74. https://doi.org/10.1016/0092-8674(92)90416-a.

    Article  CAS  PubMed  Google Scholar 

  35. Barr AR, et al. DNA damage during S-phase mediates the proliferation-quiescence decision in the subsequent G1 via p21 expression. Nat Commun. 2017;8:14728. https://doi.org/10.1038/ncomms14728.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Arakane F, Kallen CB, Watari H, Stayrook SE, Lewis M, Strauss JF. Steroidogenic acute regulatory protein (StAR) acts on the outside of mitochondria to stimulate steroidogenesis. Endocr Res. 1998;24(3–4):463–8. https://doi.org/10.3109/07435809809032634.

    Article  CAS  PubMed  Google Scholar 

  37. Miller WL, Auchus RJ. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocr Rev. 2011;32(1):81–151. https://doi.org/10.1210/er.2010-0013.

    Article  PubMed  Google Scholar 

  38. Djikić D, et al. Ethanol and nitric oxide modulate expression of glucocorticoid receptor in the rat adrenal cortex. Pharmacol Rep. 2012;64(4):896–901. https://doi.org/10.1016/s1734-1140(12)70884-8.

    Article  PubMed  Google Scholar 

  39. Paust H-J, et al. Expression of the glucocorticoid receptor in the human adrenal cortex. Exp Clin Endocrinol Diabetes. 2006;114(1):6–10. https://doi.org/10.1055/s-2005-873007.

    Article  CAS  PubMed  Google Scholar 

  40. Myers DA, Robertshaw D, Nathanielsz PW. Effect of bilateral splanchnic nerve section on adrenal function in the ovine fetus. Endocrinology. 1990;127(5):2328–35. https://doi.org/10.1210/endo-127-5-2328.

    Article  CAS  PubMed  Google Scholar 

  41. de Picciotto NE, et al. Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice. Aging Cell. 2016;15(3):522–30. https://doi.org/10.1111/acel.12461.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Gillen JB, Martin BJ, MacInnis MJ, Skelly LE, Tarnopolsky MA, Gibala MJ. Twelve weeks of sprint interval training improves indices of cardiometabolic health similar to traditional endurance training despite a five-fold lower exercise volume and time commitment. PLoS ONE. 2016;11(4):e0154075. https://doi.org/10.1371/journal.pone.0154075.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Rooyackers OE, Adey DB, Ades PA, Nair KS. Effect of age on in vivo rates of mitochondrial protein synthesis in human skeletal muscle. Proc Natl Acad Sci U S A. 1996;93(26):15364–9. https://doi.org/10.1073/pnas.93.26.15364.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Amato R, Gardin JF, Tooze JA, Cline JM (2022) Organ weights in relation to age and sex in cynomolgus monkeys (Macaca fascicularis). Toxicol Pathol:1926233221088283. https://doi.org/10.1177/01926233221088283.

  45. Nonaka K, et al. Correlation between telomere attrition of zona fasciculata and adrenal weight reduction in older men. J Clin Endocrinol Metab. 2020;105(3):dgz214. https://doi.org/10.1210/clinem/dgz214.

    Article  PubMed  Google Scholar 

  46. Popplewell PY, Azhar S. Effects of aging on cholesterol content and cholesterol-metabolizing enzymes in the rat adrenal gland. Endocrinology. 1987;121(1):64–73. https://doi.org/10.1210/endo-121-1-64.

    Article  CAS  PubMed  Google Scholar 

  47. Popplewell PY, Tsubokawa M, Ramachandran J, Azhar S. Differential effects of aging on adrenocorticotropin receptors, adenosine 3’5’-monophosphate response, and corticosterone secretion in adrenocortical cells from Sprague-Dawley rats. Endocrinology. 1986;119(5):2206–13. https://doi.org/10.1210/endo-119-5-2206.

    Article  CAS  PubMed  Google Scholar 

  48. Azhar S, Cao L, Reaven E. Alteration of the adrenal antioxidant defense system during aging in rats. J Clin Invest. 1995;96(3):1414–24. https://doi.org/10.1172/JCI118177.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Calabrese V, et al. Analytical approaches to the diagnosis and treatment of aging and aging-related disease: redox status and proteomics. Free Radic Res. 2015;49(5):511–24. https://doi.org/10.3109/10715762.2015.1020799.

    Article  CAS  PubMed  Google Scholar 

  50. Franke K, et al. Premature brain aging in baboons resulting from moderate fetal undernutrition. Front Aging Neurosci. 2017;9:92. https://doi.org/10.3389/fnagi.2017.00092.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Kuo AH, Li C, Huber HF, Nathanielsz PW, Clarke GD. Ageing changes in biventricular cardiac function in male and female baboons (Papio spp.). J Physiol (Lond). 2018;596(21):5083–98. https://doi.org/10.1113/JP276338.

    Article  CAS  PubMed  Google Scholar 

  52. Kuo AH, Li C, Huber HF, Clarke GD, Nathanielsz PW. Intrauterine growth restriction results in persistent vascular mismatch in adulthood. J Physiol. 2018;596(23):5777–90. https://doi.org/10.1113/JP275139.

    Article  CAS  PubMed  Google Scholar 

  53. Kuo AH, Li J, Li C, Huber HF, Nathanielsz PW, Clarke GD. Poor perinatal growth impairs baboon aortic windkessel function. J Dev Orig Health Dis. 2018;9(2):137–42. https://doi.org/10.1017/S2040174417000770.

    Article  CAS  PubMed  Google Scholar 

  54. Lomas-Soria C, et al. Maternal obesity has sex-dependent effects on insulin, glucose and lipid metabolism and the liver transcriptome in young adult rat offspring. J Physiol (Lond). 2018;596(19):4611–28. https://doi.org/10.1113/JP276372.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank Karen Moore for administrative support and to Dr. Edward Dick, Dr. Patrice Frost, Dr. Corinna Ross, and all of the staff of SNPRC for their support in animal care, veterinary procedures, and facility maintenance.

Funding

This study is supported by NIA U19AG057758, NIH P51OD011133.

Author information

Authors and Affiliations

  1. Southwest National Primate Research Center, Texas Biomedical Research Institute, 8715 W. Military, San Antonio, TX, 78227, USA

    Hillary Fries Huber, Laura A. Cox & Peter W. Nathanielsz

  2. Texas Pregnancy & Life-Course Health Research Center, Animal Science, University of Wyoming, Laramie, WY, USA

    Cun Li, Dongbin Xie & Peter W. Nathanielsz

  3. Statistics, University of Wyoming, Laramie, WY, USA

    Kenneth G. Gerow

  4. Pathology-Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA

    Thomas C. Register & Carol A. Shively

  5. Center for Precision Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA

    Laura A. Cox

Authors
  1. Hillary Fries Huber
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cun Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dongbin Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kenneth G. Gerow
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thomas C. Register
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Carol A. Shively
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Laura A. Cox
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Peter W. Nathanielsz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hillary Fries Huber.

Ethics declarations

Ethics approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the institution at which the studies were conducted and ethical approval was obtained from the Texas Biomedical Research Institute Institutional Animal Care and Use Committee (IACUC), Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC) Animal Welfare Assurance Number D16-00048.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Huber, H.F., Li, C., Xie, D. et al. Female baboon adrenal zona fasciculata and zona reticularis regulatory and functional proteins decrease across the life course. GeroScience 46, 3405–3417 (2024). https://doi.org/10.1007/s11357-024-01080-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11357-024-01080-9

Keywords

Search

Navigation