RU 486 blocks inhibitory effect of neonatal corticosterone administration on sertoli cell proliferation in mice

Cortisol/corticosterone (CORT) are typical glucocorticoids and exert an anti-stress function. p27, a cyclin-dependent kinase inhibitor, acts as a terminal factor for Sertoli cell proliferation at the prepubescent stage. Our previous study showed neonatal CORT administration increased p27-positive Sertoli cells followed by decreasing Sertoli cells in mice. The present study evaluated the effects of CORT and/or RU 486, a glucocorticoid receptor antagonist, on Sertoli cells in early life stages. CORT and/or RU 486 were subcutaneously injected to ICR mice, from postnatal days (PNDs) 1 to 10, at doses of 0.36 and 0.0006 mg/kg body weight, respectively. Testes from control, CORT-, RU 486 + CORT-, and RU 486-administered mice were evaluated on PNDs 4, 10, and 16. RU 486 administration blocked CORT-induced increase of relative p27-positive Sertoli cells, with the resultant recovery of Sertoli cell numbers to control level. RU 486 administration alone unexpectedly caused decreases in Sertoli cells. The present study is the first to reveal that activation of glucocorticoid receptors following CORT administration in early life stages is involved in p27-positive Sertoli cell and total Sertoli cell number in vivo, suggesting that appropriate glucocorticoid signaling in early life stages is required for the intact proliferation and maturation of Sertoli cells.