Endocrine Abstracts

Dehydroepiandrosterone is the most abundant steroid hormone circulating in the human body, we focused on its 7-hydroxylated derivatives. Many observations in rodents have demonstrated the anti-inflammatory and immune modulating activity of 7β-hydroxy-androst-5-enes, and on the basis of these experiments androst-5-ene-3β,7β,17β-triol is considered as a potential agent in the treatment of autoimmune diseases. In contrast to the fairly abundant information on the levels and effects of androst-5-ene-triols in experimental animals and of their the pharmacological perspective, little is known about androst-5-ene-3β,7α/β,17β-triols circulating in human blood, their regulation by hypothalamo-pituitary-adrenal axis, or their daily concentration variability. All data measured by GC/MS from our laboratory of androst-5-ene-3β,7β,17β-triol (β-AET) and androst-5-ene-3β,7α,17β-triol (α-AET) were analysed firstly basal levels from healthy men and women, concentrations during the daytime and also the physiological response to ACTH and hypoglycemia. Finally, the results from various groups of patients (schizophrenia, depression and anxiety, IgA nephropathy, tinnitus, epilepsy, multiple sclerosis, male and female smokers, women at delivery and with postpartum depression, women with Alzheimeĺs disease) compared to healthy control were compared. The local ethical committee approved the study. The range for α-AET was 0.009–0.180 nmol/l in females and 0.090–0.364 nmol/l in males; and 0.009–0.149 nmol/l for β-AET in females and 0.025–0.435 nmol/l in males. The levels in the healthy people were slightly lower for females than for males; the difference was not significant. The daily profiles showed the decrease from the morning hours to 10 pm, with small temporal increases associated with food consumption. After ACTH stimulation, the 7α-epimer concentration increased within 90 min by nearly 100% in men and about 30% in women. Whereas for the 7β-epimer no significant increase was found. Neither of the triols showed any significant stimulation by ITT. The ratios of the 7α-epimer to 7β-epimer concentrations were mostly near 1.0, slightly exceeding 2.0 only in women and in men with psychiatric diagnoses of schizophrenia or depression. We summarize some data on androst-5-ene-3β,7α/β,17β-triol concentrations under various conditions, which could help understanding impact of these hormones in human physiology and also in the development of several diseases. This study was supported by the project MHCZ–DRO (Institute of Endocrinology – EU, 00023761).