S-Nitrosoglutathione Reductase (GSNOR) Deficiency Results in Secondary Hypogonadism

Thomas A. Masterson, Himanshu Arora, Shathiyah Kulandavelu, Rona S. Carroll, Ursula B. Kaiser, Sakir H. Gultekin, Joshua M. Hare, Ranjith Ramasamy

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Background: Excess reactive oxygen species and reactive nitrogen species are implicated in male infertility and impaired spermatogenesis. Aim: To investigate the effect of excess reactive nitrogen species and nitrosative stress on testicular function and the hypothalamic-pituitary-gonadal axis using the S-nitrosoglutathione reductase-null (Gsnor−/−) mouse model. Methods: Testis size, pup number, and epididymal sperm concentration and motility of Gsnor−/− mice were compared with those of age-matched wild-type (WT) mice. Reproductive hormones testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone were compared in Gsnor−/− and WT mice. Immunofluorescence for Gsnor−/− and WT testis was performed for 3β-hydroxysteroid dehydrogenase and luteinizing hormone receptor (LHR) and compared. Human chorionic gonadotropin and gonadotropin-releasing hormone stimulation tests were performed to assess and compare testicular and pituitary functions of Gsnor−/− and WT mice. Outcomes: Evaluation of fertility and reproductive hormones in Gsnor−/− vs WT mice. Response of Gsnor−/− and WT mice to human chorionic gonadotropin and gonadotropin-releasing hormone to evaluate LH and T production. Results: Gsnor−/− mice had smaller litters (4.2 vs 8.0 pups per litter; P <.01), smaller testes (0.08 vs 0.09 g; P <.01), and decreased epididymal sperm concentration (69 vs 98 × 106; P <.05) and motility (39% vs 65%; P <.05) compared with WT mice. Serum T (44.8 vs 292.2 ng/dL; P <.05) and LH (0.03 vs 0.74 ng/mL; P =.04) were lower in Gsnor−/− than in WT mice despite similar follicle-stimulating hormone levels (63.98 vs 77.93 ng/mL; P =.20). Immunofluorescence of Gsnor−/− and WT testes showed similar staining of 3β-hydroxysteroid dehydrogenase and LHR. Human chorionic gonadotropin stimulation of Gsnor−/− mice increased serum T (>1,680 vs >1,680 ng/dL) and gonadotropin-releasing hormone stimulation increased serum LH (6.3 vs 8.9 ng/mL; P =.20) similar to WT mice. Clinical Translation: These findings provide novel insight to a possible mechanism of secondary hypogonadism from increased reactive nitrogen species and excess nitrosative stress. Strengths and Limitations: Limitations of this study are its small samples and variability in hormone levels. Conclusion: Deficiency of S-nitrosoglutathione reductase results in secondary hypogonadism, suggesting that excess nitrosative stress can affect LH production from the pituitary gland. Masterson TA, Arora H, Kulandavelu S, et al. S-Nitrosoglutathione Reductase (GSNOR) Deficiency Results in Secondary Hypogonadism. J Sex Med 2018;15:654–661.

Original languageEnglish (US)
Pages (from-to)654-661
Number of pages8
JournalJournal of Sexual Medicine
Volume15
Issue number5
DOIs
StatePublished - May 2018

Keywords

  • Nitrosative Stress
  • Reactive Nitrogen Species
  • Secondary Hypogonadism

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology
  • Urology

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