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

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

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;XX:XXX–XXX.

Original languageEnglish (US)
JournalJournal of Sexual Medicine
DOIs
StateAccepted/In press - Jan 1 2018
Externally publishedYes

Fingerprint

glutathione-independent formaldehyde dehydrogenase
Hypogonadism
Luteinizing Hormone
Reactive Nitrogen Species
Gonadotropin-Releasing Hormone
Hormones
Chorionic Gonadotropin
Testis
3-Hydroxysteroid Dehydrogenases
LH Receptors
Sperm Motility
Male Infertility
Follicle Stimulating Hormone
Pituitary Gland
Spermatogenesis

Keywords

  • Nitrosative Stress
  • Reactive Nitrogen Species
  • Secondary Hypogonadism

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology
  • Urology

Cite this

Masterson, T. A., Arora, H., Kulandavelu, S., Carroll, R. S., Kaiser, U. B., Gultekin, S., ... Ramasamy, R. (Accepted/In press). S-Nitrosoglutathione Reductase (GSNOR) Deficiency Results in Secondary Hypogonadism. Journal of Sexual Medicine. https://doi.org/10.1016/j.jsxm.2018.03.002

S-Nitrosoglutathione Reductase (GSNOR) Deficiency Results in Secondary Hypogonadism. / Masterson, Thomas A.; Arora, Himanshu; Kulandavelu, Shathiyah; Carroll, Rona S.; Kaiser, Ursula B.; Gultekin, Sakir; Hare, Joshua M.; Ramasamy, Ranjith.

In: Journal of Sexual Medicine, 01.01.2018.

Research output: Contribution to journalArticle

Masterson, TA, Arora, H, Kulandavelu, S, Carroll, RS, Kaiser, UB, Gultekin, S, Hare, JM & Ramasamy, R 2018, 'S-Nitrosoglutathione Reductase (GSNOR) Deficiency Results in Secondary Hypogonadism', Journal of Sexual Medicine. https://doi.org/10.1016/j.jsxm.2018.03.002
Masterson, Thomas A. ; Arora, Himanshu ; Kulandavelu, Shathiyah ; Carroll, Rona S. ; Kaiser, Ursula B. ; Gultekin, Sakir ; Hare, Joshua M. ; Ramasamy, Ranjith. / S-Nitrosoglutathione Reductase (GSNOR) Deficiency Results in Secondary Hypogonadism. In: Journal of Sexual Medicine. 2018.
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AU - Arora, Himanshu

AU - Kulandavelu, Shathiyah

AU - Carroll, Rona S.

AU - Kaiser, Ursula B.

AU - Gultekin, Sakir

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N2 - 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;XX:XXX–XXX.

AB - 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;XX:XXX–XXX.

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