Impact of nandrolone decanoate on gene expression in endocrine systems related to the adverse effects of anabolic androgenic steroids.
Elite athletes, body builders and adolescents misuse anabolic-androgenic steroids (AAS) in order to increase muscle mass or to enhance physical endurance and braveness. The high doses misused are associated with numerous adverse effects. The purpose of this study was to evaluate the impact of chronic supratherapeutic AAS treatment on circulating hormones and gene expression in peripheral tissues related to such adverse effects. Quantitative real-time PCR was used to measure expression levels of in total 37 genes (including peptide hormones, cell membrane receptors, nuclear receptors, steroid synthesising enzymes and other enzymes) in the pituitary, testes, adrenals, adipose tissue, kidneys and liver of male Sprague-Dawley rats after 14-day administration of the AAS nandrolone decanoate, 3 or 15 mg/kg. Plasma glucose and levels of adrenocorticotropic hormone (ACTH), adiponectin, corticosterone, ghrelin, insulin and leptin were also measured. We found several expected effects on the hypothalamic-pituitary-gonadal axis, while the treatment also caused a number of other not previously identified changes in circulating factors and gene transcription levels such as the dose-dependent reduction of the beta(3)-adrenergic receptor in adipose tissue, reduction of both circulating and mRNA levels of adiponectin, up-regulation of both hydroxymethylglutaryl-CoA-reductase, the rate-limiting enzyme in de novo synthesis of cholesterol, and the receptor for ACTH in the adrenals. The results provide evidence for wide ranging effects of AAS on the hypothalamic-pituitary-adrenal axis, adipose tissue and substrates of the renal control of blood pressure.
Alsiö
Johan
J
Department of Neuroscience, Functional Pharmacology, Uppsala University, BMC, Uppsala, Sweden. johan.alsio@neuro.uu.se
Birgner
Carolina
C
Björkblom
Lars
L
Isaksson
Pernilla
P
Bergström
Lena
L
Schiöth
Helgi B
HB
Lindblom
Jonas
J
D045930:Anabolic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004703:Endocrine System / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D008297:Male; D009277:Nandrolone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077603:Nandrolone Decanoate; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D045930:Anabolic Agents; D009277:Nandrolone; D000077603:Nandrolone Decanoate