Glucocorticoid agonistic and antagonistic effects of mifepristone and onapristone on thymocyte subset composition and CD26/dipeptidyl peptidase IV activity in infant male rats.
Antiglucocorticoid activities of two antigestagens-antiglucocorticoids (AGs)-mifepristone and onapristone-were tested in hydrocortisone-treated suckling male rats. Hydrocortisone (HC) treatment in vivo resulted in (1) reduction of the relative thymus weight and absolute thymocyte counts; (2) relative decrease of the CD4(+)CD8(+) thymocyte proportion accompanied by an increase of single-positive and double negative thymocyte populations, the latter of which contained large CD3-negative cells expressing a high level of CD26 on their surface; (3) increase of specific dipeptidyl peptidase IV (DPP IV) activity in thymocyte homogenates. Both AGs suppressed the systems (1) and (2) to a comparable extent. When administered alone, mifepristone and onapristone at higher doses exhibited a slight thymolytic effect as revealed by the reduction of the relative thymus weight and thymocyte counts, accompanied by some reduction of the numbers of cycling thymocytes. These effects were limited to the early postnatal period (days 12-17). A comparable agonistic effect of AGs was not observed in systems (2) and (3). Neither HC nor AGs influenced the sialylation pattern of thymocyte membrane bound CD26/DPP IV, which was exclusively of alpha2,6-type, as demonstrated by analytical isoelectric focusing (IEF) and PAGE analysis in combination with the application of neuraminidases, specific lectins and histochemical staining for DPP IV activity in the gels.
Kraml
Jirí
J
Institute of Medical Biochemistry, First Faculty of Medicine, Charles University, Kateøinská 32, 121 08 Prague 2, Czech Republic. kraml@cesnet.cz
Kolínská
Jirina
J
Sinkora
Jirí
J
Zákostelecká
Marie
M
Kadlecová
Libuse
L
Hirsová
Dana
D
Nosková
Lenka
L
D000818:Animals; D000831:Animals, Newborn; D015704:CD4 Antigens / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D016827:CD8 Antigens / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002452:Cell Count; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D005938:Glucocorticoids / Q000819:agonists* / Q000037:antagonists & inhibitors*; D006067:Gonanes / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology; D008297:Male; D015735:Mifepristone / Q000494:pharmacology*; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology
D015704:CD4 Antigens; D016827:CD8 Antigens; D005938:Glucocorticoids; D006067:Gonanes; D015735:Mifepristone; D018819:Dipeptidyl Peptidase 4; C053238:onapristone; D006854:Hydrocortisone