Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8967261 | Domestic Animal Endocrinology | 2005 | 15 Pages |
Abstract
To provide insight into potential mechanisms contributing to the various biological responses of cattle to treatment with progesterone, norgestomet, and melengestrol acetate (MGA), MCF-7 cells were utilized to determine the relative binding affinity of the progesterone receptor for MGA, norgestomet, progesterone, and a progesterone agonist (R5020), and to determine if progesterone, MGA, or norgestomet have estrogenic and/or anti-estrogenic activities. The progesterone receptor had greater affinity (P < 0.05) for MGA, R5020, and norgestomet than for progesterone; and the affinity for norgestomet exceeded (P < 0.05) that of MGA and R5020. Estrogen stimulates proliferation of MCF-7 cells; therefore these cells have been utilized as a bioassay to detect estrogenic and anti-estrogenic activity. Progesterone (10â11 to 10â5Â M) did not promote cellular proliferation. However, MGA (10â8, 10â7, and 10â6Â M) increased (P < 0.05) cell proliferation compared to the control group (10â11 to 10â9 and 10â5Â M MGA did not stimulate cell proliferation), and MGA-induced cell proliferation (10â8Â M) was reduced (P = 0.095) by an estradiol antagonist (ICI 182,780; ICI). Cellular proliferation increased (P < 0.05) with norgestomet (10â5Â M) compared to the control group (10â11 to 10â6Â M norgestomet did not stimulate cell proliferation) and the increased proliferation was decreased (P < 0.05) by ICI. Neither progesterone nor MGA demonstrated anti-estrogenic activity. Norgestomet (10â10 to 10â6Â M) did reduce (P < 0.05) maximal estrogen-stimulated cell proliferation, but not to basal levels. In summary, the affinities of the progesterone receptor for norgestomet, MGA, and progesterone are consistent with their effective dose to inhibit ovulation in vivo, but their progestin and their estrogenic/anti-estrogenic activities cannot fully explain why progesterone and norgestomet are more capable of reprogramming the reproductive axis in anestrous postpartum cows compared to MGA.
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Authors
George A. Perry, Wade V. Welshons, Rebecca C. Bott, Michael F. Smith,