Chronic treatment with sildenafil stimulates Leydig cell and testosterone secretion

Authors: Saraiva, Karina Lidianne Alcântara; Silva, Amanda Karolina Soares E.¹; Wanderley, Maria Inês²; De Araújo, Araken Almeida³; De Souza, José Roberto Botelho⁴; Peixoto, Christina Alves

Source: International Journal of Experimental Pathology, Volume 90, Number 4, August 2009 , pp. 454-462(9)

Publisher: Wiley-Blackwell

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Abstract:

Summary

The phosphodiesterase type 5 (PDE5) inhibitor, Sildenafil, is a novel, oral treatment approach for pulmonary hypertension. As Leydig cells present PDE5, this study was conducted to investigate the effects of the chronic treatment with Sildenafil (25 mg/kg) on male Swiss Webster mice steroidogenesis. After a 4-week long experimental design, Leydig cells were analysed by morphological and immunocytochemical procedures. Serum testosterone was assayed by radioimmunoassay. Leydig cells presented noteworthy ultrastructural alterations, such as a vesicular smooth endoplasmic reticulum, large vacuoles scattered through the cytoplasm, enlarged mitochondria with discontinue cristaes and whorle membranes with vesicles at the periphery, which are typical characteristics of an activated steroid-secreting cell. Important immunocytochemical labelling for steroidogenic acute regulatory protein, cytochrome P450 side-chain cleavage enzyme and testosterone were detected in isolated Leydig cells. In addition, Sildenafil-treated mice showed significant increased levels of total testosterone. The results obtained in the present study are consistent with the hypothesis that the accumulation of cyclic guanosine monophosphate by PDE5 inhibition could be involved in the androgen biosynthesis stimulation. Important clinical implications of hormonal disorders should be taken into account for patients with pulmonary hypertension.

Keywords: Leydig cells; P450scc; sildenafil; StAR; steroidogenesis; testosterone

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2613.2009.00660.x

Affiliations: 1: Laboratório de Ultraestrutura do Centro de Pesquisas Aggeu Magalhães (FIOCRUZ) 2: Departamento de Fisiologia e Farmacologia da Universidade Federal de Pernambuco 3: Faculdade de Ciências Médicas da Universidade de Pernambuco 4: Departamento de Zoologia da Universidade Federal de Pernambuco, Recife, Brazil

Publication date: 2009-08-01

Chronic treatment with sildenafil stimulates Leydig cell and testosterone secretion

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