Affordable Access

Publisher Website

Indomethacin Inhibits Lordosis Induced by Ring A-Reduced Progestins: Possible Role of 3α-Oxoreduction in Progestin-Facilitated Lordosis

Hormones and Behavior
Publication Date
DOI: 10.1006/hbeh.1998.1457


Abstract Progestins with a δ-4-3-keto configuration bind to the progestin receptor (PR) and facilitate estrous behavior in estrogen-primed rats. Some ring A-reduced progestins [5α-dihydroprogesterone (αDHP), allopregnanolone, and epipregnanolone] are more potent estrus-inducing agents than progesterone when iv injected despite their lower affinity for the PR. Yet the estrus-inducing action of such progestins is reduced by the antiprogestin RU486, suggesting that binding to the PR is required for this effect. Because allo- and epi-pregnanolone are oxidized to α- and βDHP, respectively, by 3α-hydroxysteroid oxo-reductase (3αHSOR), part of their estrus-inducing action may occur through the binding of such DHPs to the PR. Conversely, because 3αHSOR reduces α- and βDHP to allo- or epi-pregnanolone, both of which exert membrane effects, the estrus-inducing effect of DHPs may involve actions independent of the PR. To test these possibilities we assessed the effect of indomethacin, a blocker of 3αHSOR, on the estrus-inducing action of such progestins. Because indomethacin also inhibits cyclooxygenases, we selected a dose and treatment schedule that does not interfere with prostaglandin-mediated brain processes (e.g., LHRH release). Indomethacin did not significantly modify the effect of progesterone or megestrol acetate on lordosis. Yet, it significantly reduced the action of all ring A-reduced progestins. Results suggest that: (a) oxidation is essential for lordosis facilitation by 3α-pregnanolones and (b) reduction of 3-keto progestins generates 3α-hydroxy metabolites which synergize with processes triggered by occupation of the PR by 3-keto progestins. The possible participation in this response of other events influenced by indomethacin (e.g., prostaglandin or melatonin synthesis) is discussed.

There are no comments yet on this publication. Be the first to share your thoughts.


Seen <100 times