In:
Andrology, Wiley, Vol. 5, No. 3 ( 2017-05), p. 486-494
Abstract:
Estradiol (E 2 ) is normally metabolized to hydroxyestradiols and methoxyestradiols by CYP 1A1, CYP 1B1 and COMT . However, an altered production of these metabolites by a disturbed expression of these enzymes is associated with reproductive and non‐reproductive pathologies. In vitro studies suggest that increased hydroxyestradiols and methoxyestradiols intratesticular generation is related to male infertility, but no studies have explored whether infertile men have a disturbed testicular expression of the enzymes that generate these E 2 metabolites. The aim of this study was to assess CYP 1A1, CYP 1B1 and COMT testicular expression at m RNA and protein level in men with spermatogenic impairment. Seventeen men with primary spermatogenic failure (13 with Sertoli cell‐only syndrome and four with maturation arrest) and nine controls with normal spermatogenesis were subjected to testicular biopsy. m RNA was quantified using real‐time RT ‐ PCR and protein expression was evaluated using western blot and immunohistochemistry followed by integrated optic density analysis. Besides, the effects of hydroxyestradiols and methoxyestradiols on testosterone‐induced transcriptional activity were evaluated in TM 4 cells using a luciferase reporter assay system. Our results show that patients with Sertoli cell‐only syndrome had significantly elevated COMT expression at the m RNA level, higher COMT immunoreactivity in their seminiferous tubules and increased protein expression of the soluble COMT isoform (S‐ COMT ), whereas patients with maturation arrest had significantly elevated CYP 1A1 m RNA levels and higher CYP 1A1 immunoreactivity in interstitial space. Finally, 2‐hydroxyestradiol decreased testosterone‐induced transcriptional activity in Sertoli cells in vitro. In conclusion, male infertility is related to disturbed testicular expression of the enzymes responsible for producing hydroxyestradiols and/or methoxyestradiols. If these changes are related with increased intratesticular hydroxyestradiols and methoxyestradiols concentrations, they could elicit an impaired Sertoli cell function. Our results suggest CYP 1A1 and COMT as new potential targets in treating male infertility.
Type of Medium:
Online Resource
ISSN:
2047-2919
,
2047-2927
DOI:
10.1111/andr.2017.5.issue-3
Language:
English
Publisher:
Wiley
Publication Date:
2017
detail.hit.zdb_id:
2693844-3
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