Chronic administration of anabolic steroids disrupts pubertal onset and estrous cyclicity in rats.

Use of anabolic-androgenic steroids (AASs) is becoming increasingly popular among adolescent girls, yet the effects of AASs on female physiology and development are not well understood. The present study compared the effects of chronic exposure to three individual AASs, stanozolol (0.05-5 mg/kg), 17alpha-methyltestosterone (0.5-5 mg/kg), and methandrostenolone (0.5-5 mg/kg) on the onset of puberty and estrous cyclicity in the rat. Female rats received daily injections of AASs for 30 days (Postnatal Day [PN] 21-51). Rats receiving the highest dose of each of the AASs (5 mg/kg) displayed vaginal opening at a younger age than rats receiving the oil vehicle. The day of first vaginal estrus was delayed in rats receiving stanozolol (5 mg/kg) or 17alpha-methyltestosterone (0.5-5 mg/kg) but not in rats receiving methandrostenolone. At the highest dose (5 mg/kg), each of the AASs reduced the incidence of regular estrous cyclicity during the treatment period. Concurrent administration (on PN21-51) of the androgen receptor antagonist, flutamide (10 mg/kg, twice daily), reversed the effects of 17alpha-methyltestosterone (5 mg/kg) on vaginal opening. Flutamide administration also eliminated the effects of stanozolol (5 mg/kg) and 17alpha-methyltestosterone (5 mg/kg) on the day of first vaginal estrus. In contrast, rats receiving flutamide and methandrostenolone (5 mg/kg) exhibited first vaginal estrus earlier than controls. The present results indicate that chronic exposure to AASs during development has deleterious effects on the female neuroendocrine axis and that these effects appear be mediated via multiple mechanisms.

Serotonin modulates offensive attack in adolescent anabolic steroid-treated hamsters.

Chronic anabolic-androgenic steroid (AAS) treatment during adolescence facilitates offensive aggression in male Syrian hamsters (Mesocricetus auratus). The current study assessed whether adolescent AAS-facilitated offensive attack was modulated by serotonin (5-HT) and if AAS exposure during this developmental period influenced 5-HT innervation to areas of hamster brain implicated in aggressive behavior. In a first experiment, hamsters were administered high-dose AAS throughout adolescence, and then scored for offensive attack following the systemic administration of saline or fluoxetine, a selective 5-HT reuptake inhibitor. Saline-treated hamsters showed high levels of offensive attack, while treatment with fluoxetine attenuated the AAS-facilitated aggressive response. In a second experiment,were administered high-dose AAS or sesame oil throughout adolescence, tested for offensive attack and then examined for differences in 5-HT innervation to areas of the hamster brain important for aggression. Aggressive AAS-treated hamsters showed significant reductions in the number of 5-HT immunoreactive (5-HT-ir) varicosities and fibers in several of these areas, most notably the anterior hypothalamus (AH), ventrolateral hypothalamus (VLH) and medial amygdala (MeA). However, no differences in 5-HT afferent innervation were found in other aggression areas, such as the bed nucleus of the stria terminalis (BNST) and lateral septum (LS). Together, these results support a role for altered 5-HT innervation and function in adolescent AAS-facilitated offensive aggression.

Glucocorticoid antagonism by exercise and androgenic-anabolic steroids.

This work evaluated the anticatabolic capacity of androgenic-anabolic steroids and exercise (contractile activity) in inhibiting skeletal muscle atrophy associated with excessive levels of circulating glucocorticoids. With androgenic-anabolic steroids, most binding studies indicate that they have very low binding specificity for the glucocorticoid receptor. Androgens may interact through their own receptor to interfere with glucocorticoid functioning at the gene level, but this remains unproven. Current literature suggests that androgens do not prevent atrophy but may retard growth suppression accompanying glucocorticoid treatment. With exercise, functional overload, resistance, and endurance types of training are capable of preventing muscle atrophy from glucocorticoids. Androgen and glucocorticoid-receptor binding and glucocorticoid-receptor activation studies have, thus far, not established that atrophy prevention is mediated through the receptor. In conclusion, the role of androgenic-anabolic steroids as glucocorticoid antagonists requires further study. Study of the effects of exercise on muscle gene expression of glucocorticoid-inducible proteins is needed to gain additional understanding of this mechanism of atrophy prevention.