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Chronic treatment with sildenafil stimulates Leydig cell and testosterone secretion
Author(s) -
Saraiva Karina Lidianne Alcântara,
Silva Amanda Karolina Soares E.,
Wanderley Maria Inês,
De Araújo Araken Almeida,
De Souza José Roberto Botelho,
Peixoto Christina Alves
Publication year - 2009
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/j.1365-2613.2009.00660.x
Subject(s) - medicine , leydig cell , endocrinology , cholesterol side chain cleavage enzyme , testosterone (patch) , sildenafil , steroidogenic acute regulatory protein , cyclic guanosine monophosphate , endoplasmic reticulum , cgmp specific phosphodiesterase type 5 , androgen , mitochondrion , vacuole , biology , chemistry , cytoplasm , hormone , luteinizing hormone , microbiology and biotechnology , cytochrome p450 , metabolism , biochemistry , nitric oxide , messenger rna , gene
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.