title: Structural requirements for steroid inhibition of sheep lymphocyte mitogenesis in vitro.
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.
mesh_terms: D019326:17-alpha-Hydroxyprogesterone; D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000735:Androstenedione / Q000494:pharmacology; D000818:Animals; D006908:Hydroxyprogesterones / Q000494:pharmacology; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects*; D010835:Phytohemagglutinins / Q000494:pharmacology; D045167:Progesterone Congeners / Q000494:pharmacology; D012756:Sheep; D013256:Steroids / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000305:Adrenal Cortex Hormones; D006908:Hydroxyprogesterones; D010835:Phytohemagglutinins; D045167:Progesterone Congeners; D013256:Steroids; D000735:Androstenedione; D019326:17-alpha-Hydroxyprogesterone