Differential age-related changes of hypothalamus pituitary adrenal axis hormones in healthy women and men - Role of interleukin 6

Aging is accompanied by marked changes of steroid hormone levels which vary among women and men. The age-related increase of cytokines such as interle ukin (IL)- 6 may modulate the endocrine system. We aimed to investigate the role of IL-6 for the gender-specific changes of acrophase steroid hormone secretion in healthy subjects during aging. Out of 120 healthy subjects, 60 men and 48 women (non luteal phase) were recruited (age: 18 to 75 years). Age was positively correlated with IL-6 (female and male: p<0.001) and adre nocorticotropic hormone (ACTH) in women only (p<0.001). Age was negatively correlated with progesterone (female and male: p<0.001), cortisol (only fem ale: p=0.003), androstenedione (female and male: p<0.001), but not 17OH pro gesterone. After correction for IL-6, the age related decrease of steroid h ormones was blunted in both gender groups except for androstenedione (femal e and male: p<0.005). Furthermore, the ratio of serum cortisol to plasma AC TH decreased with age only in women but not in men (female: pi 0.001). Corr ection for IL 6 did not markedly change the negative interrelationship betw een age and the mentioned ratio in these women. However, a linear regressio n analysis revealed that the increase of ACTH in relation to cortisol depen ds on serum free testosterone in men (p=0.042) End on serum free 17<beta>-e stradiol (p<0.001) together with serum IL-6 in women (p=0.021). In conclusi on, IL-6 plays an important role for acrophase pituitary and peripheral hor mone secretion in women only. The gender-specific changes of cortisol in re lation to ACTH depend on the age-related decrease of the respective sex hor mone in both gender groups and the increase of IL-6 in women. This study un derlines the hormone-like role of IL-6 in the aging process of the endocrin e system in women.