Testosterone regulates granzyme K expression in rat testes

Objective. Testosterone depletion induces increased germ cell apoptosis in testes. However, limited studies exist on genes that regulate the germ cell apoptosis. Granzymes (GZM) are serine proteases that induce apoptosis in various tissues. Multiple granzymes, including GZMA, GZMB and GZMN, are pres...

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Autores principales: Dutta Dibyendu, Park In, Guililat Hiwot, Sang Samuel, Talapatra Arpita, Singhal Barkha, Mills Nathaniel C.
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Publicado: Sciendo 2017
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spelling oai:doaj.org-article:cd61b658639f4044b21c620afe217f1c2021-12-02T19:10:31ZTestosterone regulates granzyme K expression in rat testes1336-032910.1515/enr-2017-0020https://doaj.org/article/cd61b658639f4044b21c620afe217f1c2017-10-01T00:00:00Zhttps://doi.org/10.1515/enr-2017-0020https://doaj.org/toc/1336-0329Objective. Testosterone depletion induces increased germ cell apoptosis in testes. However, limited studies exist on genes that regulate the germ cell apoptosis. Granzymes (GZM) are serine proteases that induce apoptosis in various tissues. Multiple granzymes, including GZMA, GZMB and GZMN, are present in testes. Th us, we investigated which granzyme may be testosterone responsive and possibly may have a role in germ cell apoptosis aft er testosterone depletion. Methods. Ethylene dimethane sulfonate (EDS), a toxicant that selectively ablates the Leydig cells, was injected into rats to withdraw the testosterone. The testosterone depletion effects after 7 days post-EDS were verified by replacing the testosterone exogenously into EDS-treated rats. Serum or testicular testosterone was measured by radioimmunoassay. Using qPCR, mRNAs of granzyme variants in testes were quantified. The germ cell apoptosis was identified by TUNEL assay and the localization of GZMK was by immunohistochemistry. Results. EDS treatment eliminated the Leydig cells and depleted serum and testicular testosterone. At 7 days post-EDS, testis weights were reduced 18% with increased germ cell apoptosis plus elevation GZMK expression. GZMK was not associated with TUNEL-positive cells, but was localized to stripped cytoplasm of spermatids. In addition, apoptotic round spermatids were observed in the caput epididymis. Conclusions. GZMK expression in testes is testosterone dependent. GZMK is located adjacent to germ cells in seminiferous tubules and the presence of apoptotic round spermatids in the epididymis suggest its role in the degradation of microtubules in ectoplasmic specializations. Thus, overexpression of GZMK may indirectly regulate germ cell apoptosis by premature release of round spermatids from seminiferous tubule lumen.Dutta DibyenduPark InGuililat HiwotSang SamuelTalapatra ArpitaSinghal BarkhaMills Nathaniel C.Sciendoarticleapoptosisethylene dimethane sulfonateepididymisblood-testis barrierround spermatidstransition protein 1Diseases of the endocrine glands. Clinical endocrinologyRC648-665ENEndocrine Regulations, Vol 51, Iss 4, Pp 193-204 (2017)
institution DOAJ
collection DOAJ
language EN
topic apoptosis
ethylene dimethane sulfonate
epididymis
blood-testis barrier
round spermatids
transition protein 1
Diseases of the endocrine glands. Clinical endocrinology
RC648-665
spellingShingle apoptosis
ethylene dimethane sulfonate
epididymis
blood-testis barrier
round spermatids
transition protein 1
Diseases of the endocrine glands. Clinical endocrinology
RC648-665
Dutta Dibyendu
Park In
Guililat Hiwot
Sang Samuel
Talapatra Arpita
Singhal Barkha
Mills Nathaniel C.
Testosterone regulates granzyme K expression in rat testes
description Objective. Testosterone depletion induces increased germ cell apoptosis in testes. However, limited studies exist on genes that regulate the germ cell apoptosis. Granzymes (GZM) are serine proteases that induce apoptosis in various tissues. Multiple granzymes, including GZMA, GZMB and GZMN, are present in testes. Th us, we investigated which granzyme may be testosterone responsive and possibly may have a role in germ cell apoptosis aft er testosterone depletion. Methods. Ethylene dimethane sulfonate (EDS), a toxicant that selectively ablates the Leydig cells, was injected into rats to withdraw the testosterone. The testosterone depletion effects after 7 days post-EDS were verified by replacing the testosterone exogenously into EDS-treated rats. Serum or testicular testosterone was measured by radioimmunoassay. Using qPCR, mRNAs of granzyme variants in testes were quantified. The germ cell apoptosis was identified by TUNEL assay and the localization of GZMK was by immunohistochemistry. Results. EDS treatment eliminated the Leydig cells and depleted serum and testicular testosterone. At 7 days post-EDS, testis weights were reduced 18% with increased germ cell apoptosis plus elevation GZMK expression. GZMK was not associated with TUNEL-positive cells, but was localized to stripped cytoplasm of spermatids. In addition, apoptotic round spermatids were observed in the caput epididymis. Conclusions. GZMK expression in testes is testosterone dependent. GZMK is located adjacent to germ cells in seminiferous tubules and the presence of apoptotic round spermatids in the epididymis suggest its role in the degradation of microtubules in ectoplasmic specializations. Thus, overexpression of GZMK may indirectly regulate germ cell apoptosis by premature release of round spermatids from seminiferous tubule lumen.
format article
author Dutta Dibyendu
Park In
Guililat Hiwot
Sang Samuel
Talapatra Arpita
Singhal Barkha
Mills Nathaniel C.
author_facet Dutta Dibyendu
Park In
Guililat Hiwot
Sang Samuel
Talapatra Arpita
Singhal Barkha
Mills Nathaniel C.
author_sort Dutta Dibyendu
title Testosterone regulates granzyme K expression in rat testes
title_short Testosterone regulates granzyme K expression in rat testes
title_full Testosterone regulates granzyme K expression in rat testes
title_fullStr Testosterone regulates granzyme K expression in rat testes
title_full_unstemmed Testosterone regulates granzyme K expression in rat testes
title_sort testosterone regulates granzyme k expression in rat testes
publisher Sciendo
publishDate 2017
url https://doaj.org/article/cd61b658639f4044b21c620afe217f1c
work_keys_str_mv AT duttadibyendu testosteroneregulatesgranzymekexpressioninrattestes
AT parkin testosteroneregulatesgranzymekexpressioninrattestes
AT guililathiwot testosteroneregulatesgranzymekexpressioninrattestes
AT sangsamuel testosteroneregulatesgranzymekexpressioninrattestes
AT talapatraarpita testosteroneregulatesgranzymekexpressioninrattestes
AT singhalbarkha testosteroneregulatesgranzymekexpressioninrattestes
AT millsnathanielc testosteroneregulatesgranzymekexpressioninrattestes
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