Cyproterone acetate affects protamine gene expression in the testis of adult male rat.
The temporal effects of oral administration of cyproterone acetate (CPA), a progestational androgen receptor blocker, were studied on the fertility of adult male rat sires, at a dose of 20 mg kg-1 day-1 after 15 days of gavage. The treatment reduced the fertility and weights of accessory sex glands, without altering the serum levels of luteinizing hormone, follicle-stimulating hormone (FSH) and testosterone (T). Sperm counts were significantly reduced after treatment. Several changes were evident in caput epididymal sperm chromatin in treated rats. The in vitro decondensation rates of sperm chromatin and total fluorescent acridine orange (AO) dye uptake were enhanced. The fluorescent AO dye uptake by the double- and single-stranded sperm chromatin increased. The uptake of thiol-specific monobromobimane fluorescent dye by sperm chromatin was significantly reduced. Sperm of treated rats exhibited hypoprotamination. Protamine levels in the testis were significantly reduced after treatment. Androgen-binding protein (ABP) expression was significantly reduced in testis after treatment. A slight but significant increase was observed in cyclic AMP immunoexpression in testis after treatment. The expression and levels of transition proteins 1 (TP1) and 2 (TP2) as well as cyclic AMP response element modulator protein-tau were maintained at control levels in the testis of treated rats. The present study reports that androgen receptor occupation by CPA preferentially reduces the levels of spermatidal protamine in testis and spermatozoa involved in nuclear chromatin condensation. It is inferred that ABP could be mediating the effects of T in modulating the sequential expression of TPs and protamines during nuclear chromatin condensation. It is likely that indirect effects of T involve its aromatization in spermatids.
Aleem
Mukhtar
M
Department of Neuroendocrinology, National Institute for Research in Reproductive Health (ICMR), Mumbai 400 012, India.
Padwal
Varsha
V
Choudhari
Jyoti
J
Balasinor
Nafisa
N
Parte
Priyanka
P
Gill-Sharma
Manjeet
M
D000726:Androgen Antagonists / Q000494:pharmacology*; D000818:Animals; D003272:Contraceptive Agents, Male / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D051786:Cyclic AMP Response Element Modulator; D017373:Cyproterone Acetate / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D015870:Gene Expression; D008297:Male; D011479:Protamines / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012728:Sex Chromatin / Q000378:metabolism*; D013076:Sperm Count; D013091:Spermatogenesis / Q000502:physiology; D013094:Spermatozoa / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000502:physiology
D000726:Androgen Antagonists; D003272:Contraceptive Agents, Male; D004268:DNA-Binding Proteins; D011479:Protamines; D051786:Cyclic AMP Response Element Modulator; D013739:Testosterone; D017373:Cyproterone Acetate; D000242:Cyclic AMP