Endocrine Abstracts

Identification of pure neural androgenic effects is difficult due to 1) regional distribution of androgen receptors (AR) in the CNS; 2) cross-talk between molecular pathways of steroid hormone signalling, and 3) chemical nature and biotransformation of androgens in the CNS. Testosterone is transformed in the CNS by 5α-reductase and aromatase to the pure AR-agonist dihydrotestosterone (DHT) and the estrogen receptor-agonist estradiol, respectively. Decreased sexual activity is a symptom of hypogonadism, whereas anxiety and poor control of pituitary-adrenal responsiveness to stress are hallmarks of affective disorders (e.g. major depression). Age-related androgen deficiency has been associated with affective disorders, and androgens have been sporadically used as treatment. Three androgens with different pharmacological profiles were investigated in rats to elucidate whether 1) biotransformation to estrogens and 2) pronounced anabolic properties differentially contribute to behavioural and neuroendocrine actions. We used the aromatizable and 5α-reducible testosterone and the non-aromatizable dihydrotestosterone as well as the synthetic steroid anadrol (oxymetholone), a 5α-reduced androgen with pronounced anabolic properties. By chronic administration in castrated rats only testosterone was able to fully restore mounting activity to the level seen in intact rats, the non-aromatizable AR-agonist DHT showed merely a trend towards induction of sexual behaviour, while anadrol failed to induce male sexual activity. Anadrol displayed significant anxiolytic effects, whereas testosterone was effective only at higher doses; DHT failed to produce anxiolysis. Stress-induced cortico-sterone secretion was suppressed in all treatment groups, but most pronounced under testosterone. The results of this comparative examination of pure AR-agonists (DHT), aromatizable androgens (testosterone) and androgenic-anabolic steroids (anadrol) indicate differential neurotropic profiles and, consecutively, applicability to defined neurological symptoms (e.g. sexual dysfunction, anxiety or inadequate responsiveness to emotional stress).