Ring A reductions of progestins are not essential for estrous behavior facilitation in estrogen-primed rats

In Experiment 1 six dose levels (range 0.66-2000 microg) of progesterone (P) and two synthetic progestins with a double bond at C6: megestrol acetate (MA) and chlormadinone acetate (CA), which cannot be reduced at C5, were injected to estrogen-primed (2 microg estradiol benzoate 42 h earlier) ovariectomized (ovx) rats. The three progestins elicited significant lordosis and proceptive behaviors. Potency analysis showed that MA was the most potent progestin for stimulating estrous behavior, followed by P and CA. These results suggest that ring A reduction of progestins to 5alpha/5beta metabolites is not essential for the facilitation of estrous behavior in ovx estrogen-primed rats. Progestins with the 3-ketone group and a double bond at C4 can also be reduced at C3 to yield 3alpha-hydroxysteroid metabolites potentially capable of stimulating estrous behavior. In Experiment 2, the relevance of the formation of 3alpha-hydroxysteroid metabolites for estrous behavior facilitation was tested by concurrently injecting indomethacin (1.5 mg), a blocker of 3alpha-hydroxysteroid oxidoreductase, with 400 microg of P, MA, or CA to ovx estrogen-primed rats. Indomethacin failed to block the stimulatory effect of these progestins on estrous behavior. These results suggest that 3-ketosteroid reduction is also not essential for estrous behavior facilitation by progestins.