Basis of norgestomet action as a progestogen in cattle.
Norgestomet is the progestational component present in Syncro-Mate-B, which is used to synchronize estrus in cattle. In post-partum cows, luteal phases anticipated to be short following first ovulation are of normal length when cows are pretreated with norgestomet. Because Syncro-Mate-B is used experimentally as a progestogen to affect uterine function, these studies were conducted to investigate how norgestomet acts at the level of the uterus. Receptor binding assays and a sensitive estrogen bioassay in tissue culture were used to address the possibility that some effects of norgestomet might be mediated through interaction of this compound with steroid hormone receptors other than the progesterone receptor (rP). The source of receptors was high-speed cytosol, prepared from bovine uterine endometrium, which was obtained from cyclic cows. Results of single-point and complete competition analyses comparing norgestomet and progesterone indicated that norgestomet competed even more effectively than did progesterone for specific binding of [3H]progesterone to rP. Results of similar studies, which compared the abilities of norgestomet and diethylstilbestrol to compete with [3H]estradiol for binding by uterine endometrial estrogen receptors (rE), provided no evidence for norgestomet competitive binding to rE. In MCF-7 breast cancer cell bioassays, norgestomet showed weak estrogenic activity, but only at concentrations greater than 1 micromolar. Finally, norgestomet did not compete with [3H]triamcinolone acetonide when present in an 100-fold excess, and only competed with [3H]dexamethasone for binding by endometrial glucocorticoid receptors (rG) when present in the micromolar range. We conclude that, at the concentrations used in synchronizing estrus, norgestomet interacts with bovine endometrium as a progestogen and that its biological actions occur through binding of this compound to rP present in target tissues.
Moffatt
R J
RJ
Department of Animal Sciences, University of Missouri, Columbia 65211.
Zollers
W G
WG
Welshons
W V
WV
Kieborz
K R
KR
Garverick
H A
HA
Smith
M F
MF
D000818:Animals; D001667:Binding, Competitive; D001943:Breast Neoplasms; D002417:Cattle / Q000502:physiology*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000378:metabolism; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D004973:Estrus Synchronization / Q000187:drug effects*; D005260:Female; D006801:Humans; D011282:Pregnenediones / Q000378:metabolism / Q000494:pharmacology*; D011374:Progesterone / Q000378:metabolism; D045167:Progesterone Congeners / Q000378:metabolism / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology; D014222:Triamcinolone Acetonide / Q000378:metabolism; D014407:Tumor Cells, Cultured
D011282:Pregnenediones; D045167:Progesterone Congeners; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D011987:Receptors, Steroid; D013629:Tamoxifen; C100284:norgestomet; D011374:Progesterone; D004958:Estradiol; D003907:Dexamethasone; D014222:Triamcinolone Acetonide