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.
González-Flores
O
O
Centro de Investigación en Reproducción Animal, CINVESTAV-Universidad Autónoma de Tlaxcala, Tlax., Mexico.
Sánchez
N
N
González-Mariscal
G
G
Beyer
C
C
D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D000818:Animals; D002715:Chlormadinone Acetate / Q000494:pharmacology; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives; D004971:Estrus / Q000187:drug effects* / Q000523:psychology; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D019290:Megestrol Acetate / Q000494:pharmacology; D010052:Ovariectomy; D010053:Ovary / Q000502:physiology; D011374:Progesterone / Q000494:pharmacology; D045167:Progesterone Congeners / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012726:Sexual Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D013329:Structure-Activity Relationship
D045167:Progesterone Congeners; D002715:Chlormadinone Acetate; C074283:estradiol 3-benzoate; D011374:Progesterone; D004958:Estradiol; D015096:3-Hydroxysteroid Dehydrogenases; C084724:3 alpha-hydroxysteroid-5 beta-oxidoreductase; D019290:Megestrol Acetate; D007213:Indomethacin