Structural requirements for steroid inhibition of sheep lymphocyte mitogenesis in vitro |
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Authors: | L D Staples R B Heap D Brown R W Marrs |
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Affiliation: | 1. AFRC Institute of Animal Physiology, Babraham, Cambridge CB2 4AT, U.K.;3. AFRC Statistics Group, Department of Applied Biology, Pembroke Street, Cambridge CB2 3DX, U.K. |
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Abstract: | The inhibitory effects of different steroids and related compounds on sheep peripheral blood lymphocytes (PBL) during exposure to the mitogen, phytohemagglutinin (PHA), have been measured by the reduction of [3H]thymidine incorporation into DNA. Dose-response curves showed that a maximum (or near maximum effect) was achieved at a steroid concentration of 12.5 microM. At this dose 19 of 41 compounds significantly reduced thymidine incorporation by activated PBL (P less than 0.01 to P less than 0.001). The greatest reduction was observed with 17-hydroxyprogesterone (-59%, i.e. reduced by 59% compared with vehicle control, 100%) greater than androstenedione greater than epitestosterone greater than estradiol-3-methyl ether greater than 20 alpha-dihydroprogesterone greater than medroxyprogesterone acetate greater than 5 beta-pregnane-3,20-dione greater than 5 alpha-pregnane-3,20-dione (-24%). Among the steroids which showed the greatest inhibitory effect, 6 had a 4-en-3-one group in ring A, 4 had a saturated ring A (pregnane or androstane) and one had a 3-methyl ether group and a phenolic ring A. The wide range of structures represented by these inhibitory steroids suggests that inhibition of lymphocyte mitogenesis involves more than one mechanism. |
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