ABSTRACT
Progesterone receptors (PR) mediate multiple aspects of female reproduction and are
important targets for reagents that can modulate progesterone-dependent events. Many
such reagents have been developed, and they range from full PR antagonists (PAs) to
compounds with mixed agonist/antagonist actions, currently known as selective progesterone
receptor modulators (SPRMs). In women and nonhuman primates, many PR antagonists suppress
estrogen-dependent mitotic activity in the endometrial glands as well as block progestational
development of the endometrium. These latter effects are tissue- and species-specific,
are most dramatic in women and nonhuman primates, and are referred to as endometrial
antiproliferative effects. Recent evidence suggests that the endometrial androgen
receptor plays an important role in these effects. For example, endometrial androgen
receptors are increased by treatment with PAs, and combination treatment with estrogen,
a PA, and an antiandrogen (flutamide) prevents the endometrial antiproliferative effect.
Various PR modulators have great promise as gynecological therapeutics, but additional
research is needed to improve our understanding of their endometrial effects.
KEYWORDS
Progesterone receptor - antagonist - agonist - endometrium - androgen receptor - endometrial
antiproliferative effect
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Robert M BrennerPh.D.
Division of Reproductive Sciences, Oregon National Primate Research Center, Oregon
Health & Sciences University
505 NW 185th Ave, Beaverton, OR 97006
Email: brennerr@ohsu.edu
