DOPİNG AGENTS: MOLECULAR UNDERSTANDİNG OF THE İMMUNOMODULATORY EFFECTS OF ANABOLİC STEROİDS

Year 2017, Volume: Volume 2 Issue: İssue 1 (1) - 2.İnternational Congress Of Forensic Toxicology, 100 - 100, 16.02.2017

Emanuela Corsını Marco Racchı

Abstract

Anabolic
drugs or anabolic steroids are molecules chemically related to testosterone,
and with similar effects in the body. Hormones have an important role in
homeostasis and function of the immune system, including sex hormones, which
appear to have distinctive and exclusive roles in the development of the immune
system and in shaping the immune responses. Evidence is accumulating on the
existence of bidirectional interactions among oxidative stress, immune and
endocrine systems and concern is warranted.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

RACK1 is the acronym for receptor for
activated C kinase 1, encoded by a gene known as GNB2L1, guanine
nucleotide-binding protein subunit beta-2-like-1. RACK1 is involved in
embryonic development, immune response, neuronal activity and addiction, and in
circadian rhythm. At the cellular level, RACK1 is involved in a variety of
signaling pathways and different aspects of cell regulation. Due to its
plethora of interaction partners, RACK1 appears to be the fulcrum of cellular
homeostasis, controlling essential cellular processes such as transcription,
epigenetics and translation, cell proliferation and growth as well as cell
spreading and cell-cell interactions. We previously demonstrated that RACK1 gene
expression is negatively regulated by glucocorticoids, and
dehydroepiandrosterone (DHEA, an endogenous anabolic androgenic steroid) has
opposite effects on RACK1 expression and on the regulation of protein kinase C
(PKC) activity involved in immune cells activation.

DHEA seems
to antagonize the effect of glucocorticoids by inducing a dose-related
up-regulation of the negative dominant glucocorticoid receptor-β (GRβ). More
recently (manuscript submitted), we demonstrated that androstenedione, testosterone,
dihydrotestosterone (DHT), in analogy to DHEA, induced an increase in RACK1
expression (both mRNA and protein) and in LPS-induced IL-8 and TNF-α
production. Furthermore, we demonstrated that by blocking the androgen receptor
(AR), DHEA-induced GRβ and RACK1 expression could be completely prevented,
posing AR at the center of the action of DHEA, further supporting the ability
of steroid hormones to modulate RACK1 expression and immune cell activation.

We suggest that any changes in steroid hormones ratio may lead to an
imbalance between the actions of these hormones, which eventually become
relevant for the expression of proteins in the signal transduction machinery
involved in key elements of the immune response. This evidence will be used to
highlights the immunomodulatory effects of anabolic drugs.

Keywords

DOPİNG AGENTS: MOLECULAR UNDERSTANDİNG OF THE İMMUNOMODULATORY EFFECTS OF ANABOLİC STEROİDS

References

• Emanuela CORSINI, Marco RACCHI Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy. Department of Drug Sciences - Pharmacology Unit, University of Pavia, Viale Taramelli 14, 27100, Pavia Italy.