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Effects of Bleomycin, Etoposide and Cisplatin Treatment on Leydig Cell Structure and Transcription of Steroidogenic Enzymes in Rat Testis
Author(s) -
Kilarkaje Narayana,
AlBader Maie
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.558.4
Subject(s) - cholesterol side chain cleavage enzyme , steroidogenic acute regulatory protein , etoposide , medicine , leydig cell , endocrinology , bleomycin , cisplatin , chemotherapy , biology , luteinizing hormone , cancer research , hormone , cytochrome p450 , gene expression , gene , biochemistry , metabolism
Anticancer chemotherapy affects pituitary‐testicular hormonal axis in humans and animals. This study investigated the effects on Leydig cells of three cycles of bleomycin, etoposide and cisplatin (0.75, 7.5, and 1.5 mg/kg, respectively; BEP) chemotherapy in rat testis. The chemotherapy has induced hyperplasia of and degenerative changes in Leydig cells at the end of BEP exposure, which remained so even after a recovery time of 63 days. The increased testicular oxidative stress at the end of the chemotherapy returned to the normal level after the recovery time. The chemotherapy has stimulated the transcription of scavenger receptor class type‐B1 ( SCARB1 ), steroidogenic acute‐regulatory protein ( StAR ), cytochrome P450 cholesterol side‐chain cleavage ( CYP11A1 ), CYP17A1, and inhibited that of 17β‐hydroxysteroid dehydrogenase ( HSD17B6 ) and CYP19A1 in association with increased cholesterol and decreased testosterone levels. After the recovery time, the chemotherapy still had inhibitory effects on the transcription of all the above genes and luteinizing hormone receptor and HSD3B1 , but not on the StAR gene. The cholesterol and testosterone levels also did not show any significant changes. The decreased testosterone level at the end of the chemotherapy was probably due to inhibition of HSD3B1 and HSD17B6 genes. In conclusion, the BEP chemotherapy induces Leydig cell hyperplasia and alters testicular steroidogenic pathway in rats (Supported by Kuwait University Grant # MA02/08 and SRUL02/13).