Administration of growth hormone and nandrolone decanoate alters mRNA expression of the GABA(B) receptor subunits as well as of the GH receptor, IGF-1, and IGF-2 in rat brain

作者：Gronbladh Alfhild^*; Johansson Jenny; Nyberg Fred; Hallberg Mathias

来源：Growth Hormone & IGF Research, 2014, 24(2-3): 60-66.

DOI：10.1016/j.ghir.2014.01.002

• Nandrolone decanoate
• Growth hormone
• Pituitary
• Hypothalamus
• GABA(B) receptors
• Insulin-like growth factors
• Growth hormone receptor
• Anabolic androgenic steroids

Objective: The illicit use of anabolic androgenic steroids (AAS), especially among young adults, is of major concern. Among AAS users it is common to combine the AAS nandrolone decanoate (ND), with intake of growth hormone (GH) and a connection between gonadal steroids and the GH system has been suggested. Both AAS and GH affect functions in the brain, for example those associated with the hypothalamus and pituitary, and several GH actions are mediated by growth factors such as insulin-like growth factor 1 (IGF-1) and insulin-like growth factor 2 (IGF-2). The GABAergic system is implicated in actions induced by AAS and previous studies have provided evidence for a link between GH and GABA(B) receptors in the brain. Our aim was to examine the impact of AAS administration and a subsequent administration of GH, on the expression of GABA(B) receptors and important GH mediators in rat brain.
Design: The aim was to investigate the CNS effects of a high-dose ND, and to study if a low, but physiological relevant, dose of GH could reverse the ND-induced effects. In the present study, male rats were administered a high dose of ND every third day during three weeks, and subsequently the rats were given recombinant human GH (rhGH) during ten days. Quantitative PCR (qPCR) was used to analyze gene expression in hypothalamus, anterior pituitary, caudate putamen, nucleus accumbens, and amygdala.
Results: In the pituitary gland, the expression of GABA(B) receptor subunits was affected differently by the steroid treatment; the GABA(B1) mRNA expression was decreased whereas a distinct elevation of the GABA(B2) expression was found. Administration of ND also caused a decrease of GHR, IGF-1, and IGF-2 mRNA expression in the pituitary while the corresponding expression in the hypothalamus, caudate putamen, nucleus accumbens, and amygdala was unaffected. The rhGH administration did not alter the GABA(B2) expression but increased the GABA(B1) gene expression in the hypothalamus as compared to the AAS treated group.
Conclusions: These results provide new insights on the impact of ND and GH on the brain and highlight the interaction of these hormones with systems influencing GABA(B) receptor expression. The physiological significance of the observed effects of these hormones is discussed.

• 出版日期2014-6