Skip to main content
SpringerLink
Log in

Age-related changes in the blood concentrations of the hypothalamic-pituitary-adrenal axis hormones in healthy men: Relations with other hormonal axes

  • Published:
Human Physiology Aims and scope Submit manuscript

Abstract

The concentrations of cortisol, its precursors, and its active form in human blood, as well as its relationship to changes in the concentration of central and peripheral hormonal regulators (a total of 36 parameters), were studied in healthy male volunteers aged 18–72 years. The study demonstrated a significant decrease in the blood concentrations of unutilized cortisol precursors (pregnenolone and progesterone) with age accompanied by the maintenance of constant total and free cortisol concentrations. We found an age-related decrease in the adrenocorticotropic hormone (ACTH) level that is a well-known pituitary stimulant of cortisol and cortisol precursor synthesis in the adrenal glands. The cortisol and ACTH levels in the age interval studied exhibited different correlations with the central and peripheral regulators of the hormonal axes. The conclusion was drawn that the cortisol level remains stable with increasing age in men, despite the decrease in the steroidogenic activity and blood ACTH level. This may be due to the imbalance in the regulation of cortisol and ACTH production by the central and peripheral regulators, especially by the hormones of the reproductive and somatotrophic axes.

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

Similar content being viewed by others

References

  1. Papadimitriou, A. and Priftis, K., Regulation of the Hypothalamic-Pituitary-Adrenal Axis, Neuroimmunomodulation, 2009, vol.16, p. 265.

    Article  CAS  PubMed  Google Scholar 

  2. Veldhuis, J., Roelfsema, F., Iranmanesh, A., et al., Basal, Pulsatile, Entropic (Patterned), and Spiky (Staccato-Like) Properties of ACTH Secretion: Impact of Age, Gender, and Body Mass Index, J. Clin. Endocr. Metab., 2009, vol. 10, p. 4045.

    Article  Google Scholar 

  3. Ferrary, M. and Mantero, F., Male Aging and Hormones: Adrenal Cortex, J. Endocr. Invest., 2005, vol. 28, p. 92.

    Google Scholar 

  4. Buford, T. and Willoughby, D., Impact of DHEA(S) and Cortisol on Immune Function in Aging: a Brief Review, Appl. Physiol. Nutr. Metab., 2008, vol. 33, p. 429.

    Article  CAS  PubMed  Google Scholar 

  5. Guazzo, E., Kirkpatrick, P., Goodyer, I., et al., Cortisol, Dehydroepiandrosterone (DHEA), and DHEA Sulfate in the Cerebrospinal Fluid of Man: Relation to Blood Levels and the Effects of Age, J. Clin Endocr. Metab., 1996, vol. 81, p. 3951.

    Article  CAS  PubMed  Google Scholar 

  6. Bergendahl, M., Iranmanesh, A., Mulligan, T., and Veldhuis, J., Impact of Age on Cortisol Secretory Dynamics Basally and as Driven by Nutrient-Withdrawal Stress, J. Clin. Endocr. Metab., p. 2000, vol. 85, p. 2203.

  7. McCann, S., Antunes-Rodrigues, J., Franci, C., et al., Role of the Hypothalamic Pituitary Adrenal Axis in the Control of the Response to Stress and Infection, Braz. J. Med. Biol. Res., 2000, vol. 33, p. 1121.

    Article  CAS  PubMed  Google Scholar 

  8. Engelmann, M., Landgraf, R., and Wotjak, C., The Hypothalamic-Neurohypophysial System Regulates the Hypothalamic-Pituitary-Adrenal Axis Under Stress: An Old Concept Revisited, Front. Neuroend., 2004, vol. 25, p. 132.

    Article  CAS  Google Scholar 

  9. Uvnas-Moberg, K. and Peterson, M., Oxitocin, a Mediator of Anti-Stress, Well-Being, Social Interaction, Growth and Healing, Z. Psyh. Med. Psychother., 2005, vol. 51, p. 57.

    Google Scholar 

  10. Ruginsk, S., da Silva, A., Ventura, R., et al., Central Actions of Glucocorticoids in the Control of Body Fluid Homeostasis: Review, Braz. J. Med. Biol. Res.-, 2009, vol. 42, p. 61.

    CAS  PubMed  Google Scholar 

  11. Bao, A., Meynen, G., and Swaab, D., The Stress System in Depression and Neurodegeneration: Focus on the Human Hypothalamus, Brain Res. Rev., 2008, vol. 57, p. 531.

    Article  CAS  PubMed  Google Scholar 

  12. Hu, G., Lian, Q., Latif, S., et al., Rapid Mechanisms of Glucocorticoid Signaling in the Luydig Cell, Steroids, 2008, vol. 73, p. 1018.

    Article  CAS  PubMed  Google Scholar 

  13. Demura, R., Kubo, O., Suzuki, R., et al., Demonstration of Activin in Normal Pituitary and in Various Human Pituitary Adenomas by Immunohistochemistry, Endocr. J., 1996, vol. 43, p. 429.

    Article  CAS  PubMed  Google Scholar 

  14. Suzuki, J., Otsuka, F., Inagaki, K., et al., Novel Action of Activin and Bone Morphogenetic Protein in Regulation Aldosterone Production by Human Adrenocortical Cells, Endocrinology, 2004, vol. 145, p. 639.

    Article  CAS  PubMed  Google Scholar 

  15. Vanttinen, T., Liu, J., Kuulasmaa, T., et al., Expressiom of Activin/Inhibin Signaling Components in the Human Adrenal Gland and the Effects of Activins and Inhibins on Adrenocortical Steroidogenesis and Apoptosis, J. Endocrinol., 2003, vol. 178, p. 479.

    Article  CAS  PubMed  Google Scholar 

  16. Farnworth, P., Wang, Y., Leembruggen, P., et al., Rodent Adrenocortical Cells Display High Affinity Binding Sites and Proteins for Inhibin A, and Express Components Required for Autocrine Signaling by Activins and Bone Morphogenetic Proteins, J. Endocrinol., 2006, vol. 188, p. 451.

    Article  CAS  PubMed  Google Scholar 

  17. Vogl, J., Hoing, A., Schuze, S., et al., Expression of Inhibins in the Endometrial Carcinoma Cell Line RL-95-2 After Stimulation with Cortisol and Estradiol, Anticancer Rs., 2007, vol. 27, p. 1989.

    CAS  Google Scholar 

  18. Nass, R. and Thorner, M., Impact of the GH-Cortisol Ratio on the Age-Dependent Changes in Body Composition, Growth Hormone and IGF Res., 2002, vol. 12, p. 147.

    Article  CAS  Google Scholar 

  19. Hofland, L., Somatostatin and Somatostatin Receptors in Cushing’s Disease, Mol. Cell. Endocr., 2008, vol. 286, p. 199.

    Article  CAS  Google Scholar 

  20. de Bruin, C., Feelders, R., Lamberts, S., et al., Somatostatin and Dopamine Receptors as Targets for Medical Treatment of Cushing’s Syndrome, Rev. Endocr. Metab. Disord., 2009, vol. 10, p. 91.

    Article  CAS  PubMed  Google Scholar 

  21. Kageyama, K., Kushibiki, M., Hanada, K., et al., Growth Hormone-Releasing Peptide-2 Stimulates Secretion and Synthesis of Adrenocorticotropic Hormone in Mouse Pituitary, Regul. Pept., 2009, vol. 158, p. 116.

    Article  CAS  PubMed  Google Scholar 

  22. Agna, A. and Monson, P., Modulation of Glucocorticoid Metabolism by the Growth Hormone — IGF-1 Axis, Clin. Endocr., 2007, vol. 66, p. 459.

    Google Scholar 

  23. Ceda, G., Dall’Aglio, E., Maggio, M., et al., Clinical Implications of the Reduced Activity of the GH-IGF-I Axis in Older Men, J. Endocr. Invest., 2005, vol. 28, p. 96.

    CAS  PubMed  Google Scholar 

  24. Giovannini, S., Marzetti, E., Borst, S., and Leeuwenburgh, C., Modulation of GH/IGF-1 Axis: Potential Strategies to Counteract Sarcopenia in Older Adults, Mech. Ageing Dev., 2008, vol. 129, p. 593.

    Article  CAS  PubMed  Google Scholar 

  25. Raposinho, P., Broqua, P., Pierroz, D., et al., Evidence That the Inhibition of Luteinizing Hormonr Secretion Exerted by Central Administration of Neuropeptide Y (NPY) in the Rat is Predominantly Mediated by the NPY-5 Receptor Subtype, Endocrinology, 1999, vol. 140, p. 4046.

    Article  CAS  PubMed  Google Scholar 

  26. Morgan, C., Rasmusson, M., Wang, S., et al., Neuropeptide-Y, Cortisol, and Subjective Distress in Humans Exposed to Acute Sress: Replication and Extention of Previous Report, Biol. Psychiatry., 2002, vol. 52, p. 136.

    Article  CAS  PubMed  Google Scholar 

  27. Konturek, S., Konturek, T., Pawlik, T., and Brzozowki, T., Brain-Gut Axis and Its Role in the Control of Food Intake, J. Physiol. Pharmacol., 2004, vol. 55, p. 137.

    CAS  PubMed  Google Scholar 

  28. Nissdorfer, G., Spinazzi, R., and Mazzocchi, G., Cholecystokinin and Adrenal-Cortex Secretion, Vitam. Horm., 2005, vol. 71, p. 433.

    Article  Google Scholar 

  29. Aoyadi, T., Kusakawa, S., Sanbe, A., et al., Enhanced Effect of Neuropeptide Y on Food Intake Caused by Blocade of the V(1A) Vasopressin Receptor, Eur. J. Pharmacol., 2009, vol. 622, p. 32.

    Article  Google Scholar 

  30. Swali, A., Walker, E., Lavery, G., et al., 11beta-Hydroxysteroid Dehydrogenase Type 1 Regulates Insulin and Glucagon Secretion in Pancreativ Islets, Diabetologia, 2008, vol. 51, p. 2003.

    Article  CAS  PubMed  Google Scholar 

  31. Wiedemann, K., Jahn, H., and Kellner, M., Effects of Natriuretic Peptides Upon Hypothalamo-Pituitary-Adrenocortical System Activity and Anxiety Behavior, Exp. Clin. Endocr. Diabetes, 2000, vol. 108, p. 5.

    CAS  Google Scholar 

  32. Yamaji, M., Tsutamoto, T., Kawahara, C., et al., Serum Cortisol as a Useful Predictor of Csrdiac Events in Patients with Chronic Heart Failure: the Impact of Oxidative Stress, Circ. Heart Fail., 2009, vol. 2, p. 608.

    Article  CAS  PubMed  Google Scholar 

  33. Auchus, J. and Rainey, W., Adrenarche—Physiology, Biochemistry and Human Disease, Clin. Endocrinol, 2004, vol. 60, p. 288.

    Article  CAS  Google Scholar 

  34. Akhtar, M., Kelly, S., and Kaderbhai, M., Cytochrome B5 Modulation of 17 Hydroxylase and 17–20 Lyase (CYP17) Activities in Steroidogenesis, J. Endocrinol, 2005, vol. 187, p. 267.

    Article  CAS  PubMed  Google Scholar 

  35. Luo, L., Chen, H., and Zirkin, B., Temporal Relationships Among Testosterone Production, Steroidogenic Acute Regulatory Protein (StAR), and P450 Side-Chain Cleavage Enzyme (P450scc) during Leidig Cell Aging, J. Androl., 2005, V. 26, p. 25.

    CAS  PubMed  Google Scholar 

  36. Audige, A., Dick, B., Frey, B., et al., Glucocorticoids and 11 Beta-Hydroxysteroid Dehydrogenase Type 2 Gene Expression in the Aging Kidney, Eur. J. Clin. Invest., 2002, vol. 32, p. 411.

    Article  CAS  PubMed  Google Scholar 

  37. Koeva, Y., Bakalska, M., Atanasova, N., et al., Age-Related Changes in the Expression of 11beta-Hydroxysteroid Dehydrogenase Type 2 in Rat Leydig Cells, Folia Histochem. Cytobiol., 2009, vol. 47, p. 281.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Moscow State University, Moscow, 119991, Russia

    I. N. Kuzina & O. V. Smirnova

  2. Russian State Medical University, Moscow, 117997, Russia

    V. V. Kilikovsky

Authors
  1. I. N. Kuzina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. V. V. Kilikovsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. O. V. Smirnova
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Original Russian Text © I.N. Kuzina, V.V. Kilikovsky, O.V. Smirnova, 2010, published in Fiziologiya Cheloveka, 2010, Vol. 36, No. 5, pp. 101–109.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kuzina, I.N., Kilikovsky, V.V. & Smirnova, O.V. Age-related changes in the blood concentrations of the hypothalamic-pituitary-adrenal axis hormones in healthy men: Relations with other hormonal axes. Hum Physiol 36, 582–589 (2010). https://doi.org/10.1134/S0362119710050105

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0362119710050105

Key words

Search

Navigation