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 interleukin (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 adrenocorticotropic hormone (ACTH) in women only (p<0.001). Age was negatively correlated with progesterone (female and male: p<0.001), cortisol (only female: p=0.003), androstenedione (female and male: p<0.001), but not 17OH progesterone. After correction for IL-6, the age-related decrease of steroid hormones was blunted in both gender groups except for androstenedione (female and male: p<0.005). Furthermore, the ratio of serum cortisol to plasma ACTH decreased with age only in women but not in men (female: p< 0.001). Correction for IL-6 did not markedly change the negative interrelationship between age and the mentioned ratio in these women. However, a linear regression analysis revealed that the increase of ACTH in relation to cortisol depends on serum free testosterone in men (p=0.042) and on serum free 17 beta-estradiol (p<0.001) together with serum IL-6 in women (p=0.021). In conclusion, IL-6 plays an important role for acrophase pituitary and peripheral hormone secretion in women only. The gender-specific changes of cortisol in relation to ACTH depend on the age-related decrease of the respective sex hormone in both gender groups and the increase of IL-6 in women. This study underlines the hormone-like role of IL-6 in the aging process of the endocrine system in women.