Dehydroepiandrosterone and 7-oxo-dehydroepiandrosterone in male reproductive health: Implications of differential regulation of human Sertoli cells metabolic profile

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Dias, TR (Author) Other; Alves, MG (Author) Other; Almeida, SP (Author) Other; Silva, J (Author) Other; barros, a (Author) FMUP; sousa, m (Author) ICBAS; Silva, BM (Author) Other; Silvestre, SM (Author) Other; Oliveira, PF (Author) ICBAS

Journal

Title: Journal of Steroid Biochemistry and Molecular Biology

Vol. 154

Pages: 1-11

ISSN: 0960-0760

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 13 Citations

Scopus - 13 Citations

Other information

Authenticus ID: P-00G-CJR

DOI: 10.1016/j.jsbmb.2015.06.004

Abstract (EN): Dehydroepiandrosterone (DHEA) is a precursor of androgen synthesis whose action is partially exerted through its metabolites. 7-Oxo-dehydroepiandrosterone (7-oxo-DHEA) is a common DHEA metabolite, non-convertible to androgens, which constitutes a promising therapeutic strategy for multiple conditions. Sertoli cells (SCs) are responsible for the support of spermatogenesis, having unique metabolic characteristics strongly modulated by androgens. Consequently, disruptions in androgen synthesis compromise SCs function and hence male fertility. We aimed to evaluate the effects of DHEA and 7-oxo-DHEA in human SCs (hSCs) metabolism and oxidative profile. To do so, hSCs were exposed to increasing concentrations of DHEA and 7-oxo-DHEA (0.025, 1 and 50 mu M) that revealed to be non-cytotoxic in these experimental conditions. We measured hSCs metabolites consumption/production by H-1 NMR, the protein expression levels of key players of the glycolytic pathway by Western blot as well as the levels of carbonyl groups, nitration and lipid peroxidation by Slot blot. The obtained data demonstrated that 7-oxo-DHEA is a more potent metabolic modulator than DHEA since it increased hSCs glycolytic flux. DHEA seem to redirect hSCs metabolism to the Krebs cycle, while 7-oxo-DHEA has some inhibitory effect in this path. The highest 7-oxo-DHEA concentrations (1 and 50 mu M) also increased lactate production, which is of extreme relevance for the successful progression of spermatogenesis in vivo. None of these steroids altered the intracellular oxidative profile of hSCs, illustrating that, at the concentrations used they do not have pro- nor antioxidant actions in hSCs. Our study represents a further step in the establishment of safe doses of DHEA and 7-oxo-DHEA to hSCs, supporting its possible use in hormonal and non-hormonal therapies against male reproductive problems.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11