Evaluation of Cortisol Resistance in Young Endurance-trained and Elderly Men
- The adrenal glands, located above the kidneys, produce hormones called glucocorticoids and mineralocorticoids. Glucocorticoids, especially the hormone cortisol, act on nearly all cells in the body with effects that are especially important to the body's stress response. They maintain heart function, blood pressure, and proper blood sugar levels, and help regulate the body's responses to infections and injury. Mineralocorticoids help to regulate salt and water levels in the body.
- Blood levels of cortisol have a natural day-to-night pattern: the highest levels occur in the morning and the lowest levels occur at night. This pattern is regulated by the hormone ACTH, which is made by the pituitary gland, and causes increased or decreased cortisol levels in response to the levels in the blood. Research has shown that older men have higher ACTH and cortisol levels than younger men, and that endurance-trained athletes have different cortisol levels than more sedentary individuals. Researchers are interested in studying these differences in cortisol levels and their potential effects on health.
- To compare cortisol levels and responses in sedentary young men and endurance-trained male athletes and elderly men.
- Healthy men between 18 and 30 years of age who have exercised less than 1 hour each week for the past 3 years.
- Healthy men between 18 and 30 years of age who have regularly run more than 45 km (28 miles) per week for at least 3 months.
- Healthy men between 65 and 80 years of age who have exercised less than 1 hour each week for the past 3 years.
- Participants will be screened with a full medical history and physical examination, as well as blood and urine samples.
- Participants will collect saliva and urine samples at home, both for cortisol measurements. Saliva samples should be collected in the evening on 2 separate days, and urine samples should be collected continuously for 12-hour intervals (7 AM to 7 PM and 7 PM to 7 AM) over a single 24-hour period. Participants will provide baseline blood samples at the National Institutes of Health when they drop off the saliva and urine samples.
- Participants will have four separate evening/overnight tests at the National Institutes of Health. At these tests, participants will take study drugs or a look-alike capsule to block the effects of only glucocorticoid, only mineralocorticoid, both glucocorticoid and mineralocorticoid, or neither. Blood, saliva, and urine samples will be collected regularly from 7 PM to 7 AM the next morning.
- Participants will have a final clinic test in which they will take dexamethasone late in the evening (11 PM to midnight) and visit the National Institutes of Health by 8 AM the next morning to provide a blood sample.
|Study Design:||Time Perspective: Prospective|
|Official Title:||Evaluation of Cortisol Resistance in Young Endurance-Trained and Elderly Men|
|Study Start Date:||January 2011|
Adrenocorticotropin (ACTH) secretion is normally exquisitely regulated through endogenous stimulation by corticotrophin-releasing hormone (CRH) and negative feedback inhibition by cortisol, resulting in a circadian rhythm of cortisol. Recent evidence suggests that older men and younger men who are endurance-trained athletes both have reduced sensitivity to negative feedback, and perhaps increased basal levels of cortisol and ACTH. To investigate these possibilities, we propose to examine multiple aspects of the hypothalamic-pituitary-adrenal axis in younger endurance trained and sedentary men, and in older sedentary men.
Subjects will collect saliva during two evenings before additional testing, and will on the same evening collect urine for twelve hours, both for cortisol measurements. Blood samples will be collected to evaluate the function of white blood cells and their responses to dexamethasone. We also will assess ACTH and cortisol responses to medications that reduce negative inhibition of ACTH. This testing will occur in the evening and will include administration of the glucocorticoid antagonist mifepristone, the mineralocorticoid antagonist spironolactone, and/or a look-alike tablet, on four occasions.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Lynnette K Nieman, M.D.||Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)|