Caspase-3 and caspase-activated deoxyribonuclease are associated with testicular germ cell apoptosis resulting from reduced intratesticular testosterone

Jong Min Kim, Shampa R. Ghosh, Alexander C P Weil, Barry R Zirkin

Research output: Contribution to journalArticle

Abstract

The purpose of the present study was to examine the possible involvement of caspase-3 and caspase-activated deoxyribonuclease in rat testicular germ cell apoptosis resulting from reduced intratesticular testosterone concentration. Adult Sprague Dawley rats received LH-suppressive testosterone-and estradiol-filled SILASTIC capsules of 2.5 and 0.1 cm, respectively, a regimen known to rapidly reduce testosterone production by the testes and to produce azoospermia within 8 wk. Germ cell internucleosomal DNA cleavage increased compared with control levels by 1 wk postimplantation and increased further through 4 wk. In situ terminal deoxynucleotidyltransferase-mediated deoxy-UTP nick end labeling revealed that spermatocytes represented the predominant apoptotic cell type. Modest immunoreactivity for active caspase-3 was localized to the cytoplasm or perinuclear region of the germ cells of control testes. After testosterone and estradiol administration, however, intense staining for caspase-3 was localized to the nuclei of spermatocytes. Western blotting revealed significantly increased caspase-3 cleavage (activation) in nuclei isolated from germ cells after rats were administered testosterone and estradiol. Cleavage of the caspase-3 substrate protein, poly(ADP-ribose) polymerase, was seen after testosterone and estradiol treatment. Additionally, the caspase-activated deoxyribonuclease protein content was significantly increased in germ cells after rats were administered testosterone and estradiol, and caspase-activated deoxyribonuclease immunoreactivity was localized to the nuclei of apoptotic spermatocytes. Taken together, these results indicate that germ cell apoptosis resulting from a reduced intratesticular testosterone concentration is caspase-3 activation dependent and suggest that the translocation of active caspase-3 and caspase-activated deoxyribonuclease to the nucleus may be involved in the induction of germ cell apoptosis.

Original languageEnglish (US)
Pages (from-to)3809-3816
Number of pages8
JournalEndocrinology
Volume142
Issue number9
DOIs
StatePublished - 2001

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Germ Cells
Caspase 3
Testosterone
Apoptosis
Estradiol
Spermatocytes
Testis
Azoospermia
DNA Cleavage
DNA Nucleotidylexotransferase
Poly(ADP-ribose) Polymerases
caspase-activated deoxyribonuclease
Capsules
Sprague Dawley Rats
Cytoplasm
Proteins
Western Blotting
Staining and Labeling

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Caspase-3 and caspase-activated deoxyribonuclease are associated with testicular germ cell apoptosis resulting from reduced intratesticular testosterone. / Kim, Jong Min; Ghosh, Shampa R.; Weil, Alexander C P; Zirkin, Barry R.

In: Endocrinology, Vol. 142, No. 9, 2001, p. 3809-3816.

Research output: Contribution to journalArticle

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