Mechanisms responsible for progesterone's protection against lordosis-inhibiting effects of restraint II. Role of progesterone metabolites.

Abstract

When ovariectomized Fischer female rats are hormonally primed with 10 μg estradiol benzoate, a 5 min restraint experience rapidly inhibits lordosis behavior. Addition of progesterone to the hormonal priming prevents this restraint-induced inhibition. In prior work, we reported evidence that progesterone receptors (PR) may contribute to this protective effect of progesterone. In the current manuscript, we provide evidence that progesterone metabolites may also contribute to progesterone's ability to reduce the effects of restraint. Ovariectomized female rats were hormonally primed with 10 μg estradiol benzoate followed 2 days later with 4.0 mg/kg of the progesterone metabolite, allopregnanolone. Allopregnanolone, administered either 4 h or 2 h before the restraint experience, was as effective as progesterone in reducing the lordosis-inhibitory effects of restraint. In the second experiment, progesterone metabolism was blocked with 50 mg/kg of the 5α-reductase inhibitor, finasteride. Surprisingly, finasteride did not prevent progesterone from reducing the effects of restraint. In a third experiment, we tested the possibility that allopregnanolone acted through metabolism to dihydroprogesterone. Rats were treated with allopregnanolone or with allopregnanolone plus the 3α-hydroxysteroid dehydrogenase inhibitor, indomethacin. Indomethacin did not prevent allopregnanolone from reducing the effects of restraint. Mechanisms are discussed whereby cross-talk between PR-mediated and metabolite-mediated events may converge in producing progesterone's attenuation of the effect of restraint.

• Authors: Chandra Suma Johnson Miryala, James Hassell, Sarah Adams, Cindy Hiegel, Ndidi Uzor, Lynda Uphouse
• Journal: Hormones and behavior (Horm Behav) Vol. 60 Issue 2 Pg. 226-32 (Jul 2011) ISSN: 1095-6867 [Electronic] United States
• PMID: 21621542 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• 5-alpha Reductase Inhibitors
• Cyclooxygenase Inhibitors
• Progestins
• Receptors, Progesterone
• Finasteride
• Pregnanolone
• Indomethacin

Topics

• 5-alpha Reductase Inhibitors (pharmacology)
• Animals
• Cyclooxygenase Inhibitors (pharmacology)
• Female
• Finasteride (pharmacology)
• Indomethacin (pharmacology)
• Ovariectomy
• Posture (physiology)
• Pregnanolone (pharmacology)
• Progestins (pharmacology)
• Rats
• Rats, Inbred F344
• Receptors, Progesterone (metabolism)
• Restraint, Physical
• Sexual Behavior, Animal (drug effects, physiology)