Influence of certain steroids on lymphocyte transformation in sheep and goats studied in vitro.

The effect of various steroids on lymphocyte transformation was tested with peripheral blood lymphocytes (PBL) from sheep and goats. Transformation was induced with phytohaemagglutinin, pokeweed mitogen and Concanavalin A, and by allogeneic lymphocytes (mixed lymphocyte culture). Progestagens, androgens and corticosteroids inhibited mitogen-induced transformation of lymphocytes from both species. With sheep PBL, progestagens and androgens inhibited transformation at high concentrations. Progesterone and its less active metabolites 5 alpha-pregnanedione and 20 alpha-dihydro-progesterone were equally inhibitory. Corticosteroids were more effective than other steroids at concentrations of less than 1 mumol/l. Oestrogens had relatively little effect with the exception of diethylstilboestrol which markedly enhanced sheep PBL responses to mitogen. Structural comparisons suggested that the most suppressive C-19 and C-21 steroids possessed 4-en-3-one configuration in ring A, and that inhibitory activity was enhanced by C-17 alpha substitution as in 17 alpha-hydroxyprogesterone. The steroid effects on PBL were largely unaffected by the reproductive status of the donor, were exerted during the early pre-replicative phase rather than at the time of new DNA synthesis, and were not attributable to cytoxicity nor to changes in intracellular thymidine pools. An exception was found with the non-steroidal oestrogen, diethylstilboestrol, which enhanced the response to mitogen-treated cultures of sheep lymphocytes at both early and late phases of the cell cycle. It is concluded that several naturally occurring steroids affect the responsiveness of PBL to mitogenic stimuli, and that progesterone and/or certain of its metabolites may be effective in vivo when present at the high concentrations found in the utero-ovarian lymphatic network draining the gravid uterus or at the trophoblast-maternal interface in the sheep and goat.