TY - JOUR
T1 - Interaction of cycloalkanoprogesterones with mammalian progesterone receptor
T2 - binding of pregna-D'-pentaranes in the calf uterine cytosol
AU - Bhakta, Amrita
AU - Herman, Michelle
AU - Levina, Inna S.
AU - Moudgil, V. K.
PY - 1993/8
Y1 - 1993/8
N2 - Pregna-D'-pentaranes (pentaranes) are modified progesterones with demonstrable progestational activity and contraceptive effect. We have examined the steroid binding characteristics of the two newly synthesized progesterone analogs, Pentarane A (16α, 17α-cyclohexanoprogesterone) and Pentarane B (6α-methyl, 16α, 17α-cyclohexanoprogesterone), and studied the nature of their interaction with progesterone receptor (PR) from the chicken oviduct and the calf uterine cytosols. Pregna-D'-pentaranes exhibited no affinity for the chick PR but interacted with the calf uterine PR as did R5020. The pentaranes, however, bound PR less tightly. R5020- or pentarane-bound PR sedimented as an 8S moiety in 8-30% linear glycerol gradients. Thermal transformation of receptor resulted in the reduction of the 8S form, and caused an increase in the binding of R5020-and progesterone-bound PR complexes to DNA-cellulose. The pentarane-bound PR bound poorly, if at all, to DNA-cellulose. Our data suggest that pentaranes exhibit both similarities and differences with natural and synthetic progestins with respect to their interaction with calf uterine PR. The lack of pentarane binding to chicken PR is reminiscent of the general phenomenon that antiprogestins (RU486, ZK98299, and Org 31710 and Org 31806) do not interact with chicken PR. Pentaranes, therefore, represent unique steroid analogs to investigate the molecular mechanism of steroid hormone action.
AB - Pregna-D'-pentaranes (pentaranes) are modified progesterones with demonstrable progestational activity and contraceptive effect. We have examined the steroid binding characteristics of the two newly synthesized progesterone analogs, Pentarane A (16α, 17α-cyclohexanoprogesterone) and Pentarane B (6α-methyl, 16α, 17α-cyclohexanoprogesterone), and studied the nature of their interaction with progesterone receptor (PR) from the chicken oviduct and the calf uterine cytosols. Pregna-D'-pentaranes exhibited no affinity for the chick PR but interacted with the calf uterine PR as did R5020. The pentaranes, however, bound PR less tightly. R5020- or pentarane-bound PR sedimented as an 8S moiety in 8-30% linear glycerol gradients. Thermal transformation of receptor resulted in the reduction of the 8S form, and caused an increase in the binding of R5020-and progesterone-bound PR complexes to DNA-cellulose. The pentarane-bound PR bound poorly, if at all, to DNA-cellulose. Our data suggest that pentaranes exhibit both similarities and differences with natural and synthetic progestins with respect to their interaction with calf uterine PR. The lack of pentarane binding to chicken PR is reminiscent of the general phenomenon that antiprogestins (RU486, ZK98299, and Org 31710 and Org 31806) do not interact with chicken PR. Pentaranes, therefore, represent unique steroid analogs to investigate the molecular mechanism of steroid hormone action.
KW - DNA binding
KW - progesterone
KW - receptors
KW - steroid analogues
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U2 - 10.1007/BF00936444
DO - 10.1007/BF00936444
M3 - Article
C2 - 8283970
AN - SCOPUS:0027380782
SN - 0300-8177
VL - 125
SP - 153
EP - 161
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
IS - 2
ER -