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Administration of growth hormone and nandrolone decanoate alters mRNA expression of the GABAB receptor subunits as well as GH receptor, IGF-1, and IGF-2 in rat brain
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
(English)Article in journal (Refereed) Submitted
Abstract [en]

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 GABAB receptors in the brain. Our aim was to examine the impact of a combined administration of AAS and GH on expression of GABAB receptors and important GH mediators in rat brain

Design: 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 GABAB receptor subunits was affected differently by the steroid treatment; the GABAB1 mRNA expression was decreased whereas a distinct elevation of the GABAB2 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 GABAB2 expression but increased the GABAB1 gene expression in the hypothalamus as compared 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 GABAB receptor expression. The physiological significance of the observed effects of these hormones is discussed.

National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-205916OAI: oai:DiVA.org:uu-205916DiVA: diva2:643366
Available from: 2013-08-27 Created: 2013-08-25 Last updated: 2014-01-22Bibliographically approved
In thesis
1. Growth Hormone and Anabolic Androgenic Steroids: Effects on Neurochemistry and Cognition
Open this publication in new window or tab >>Growth Hormone and Anabolic Androgenic Steroids: Effects on Neurochemistry and Cognition
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Growth hormone (GH) stimulates growth and metabolism but also displays profound effects on the central nervous system (CNS). GH affects neurogenesis and neuroprotection, and has been shown to counteract drug-induced apoptosis in the brain. Anabolic androgenic steroids (AAS), mainly abused for their anabolic and performance-enhancing properties, can cause several adverse effects, such as cardiovascular complications, sterility, depression, and aggression. GH and AAS are both believed to interact with several signaling systems in the CNS. The aim of this thesis was to further investigate the impact of GH and AAS on neurochemistry and cognitive functions. Recombinant human GH (rhGH) and the steroid nandrolone decanoate (ND) were administered, separately and in combination with each other, to male rats.

The results demonstrated that administration of GH improved spatial memory, assessed in a water maze test. Furthermore, GH induced alterations of the GABAB receptor mRNA expression, density, and functionality in the brain, for example in regions associated with cognition. GH also altered the mu opioid peptide (MOP) receptor, but not the delta opioid peptide (DOP) receptor functionality in the brain. Thus, some of the GH effects on cognition may involve effects on the GABAB receptors and MOP receptors. ND, on the contrary, seemed to induce impairments of memory and also altered the GABAB receptor mRNA expression in the brain. Furthermore, ND lowered the IGF-1 plasma concentrations and attenuated the IGF-1, IGF-2, and GHR mRNA expression in the pituitary. In addition, significant effects of GH and ND were found on plasma steroid concentrations, organ weight, as well as body weight.

In conclusion, this thesis contributes with further knowledge on the cognitive and neurochemical consequences of GH and ND use. The findings regarding ND are worrying considering the common use of AAS among adolescents. GH improves memory functions and affects signaling systems in the brain associated with cognition, hence the hypothesis that GH can reverse drug-induced impairments is further strengthened.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 73 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 175
Keyword
Growth hormone, anabolic androgenic steroids, nandrolone decanoate, insulin-like growth factor, GABAB, opioids, memory, water maze, autoradiography, central nervous system, rats
National Category
Pharmaceutical Sciences
Research subject
Biological Research on Drug Dependence
Identifiers
urn:nbn:se:uu:diva-206069 (URN)978-91-554-8732-4 (ISBN)
Public defence
2013-10-11, B21, Biomedical center, Husargatan 3, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2013-09-20 Created: 2013-08-27 Last updated: 2014-01-22

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