Mifepristone and ovarian function.
In summary, RU 486 has been a powerful instrument in delineating progesterone action on the ovary. However, early experiments using RU 486 must be interpreted with the understanding that systemic administration of the antiprogestin may have had extraovarian sites of action, such as at the hypothalamic-pituitary axis or at the adrenal, that in turn led to indirect ovarian responses. Treatment with progesterone, agonist, or antagonist at periods during which the ovary lacks progesterone receptors would further suggest extraovarian sites of action or nongenomic mechanisms of action. Furthermore, the dose of ligand or antagonist administered and the hormonal milieu at the time of administration may dictate the ovarian response (Espey L, personal communication). For example, low doses of exogenous progesterone may elicit a biologic response, whereas high doses are without effect or may inhibit the biologic effect observed at lower doses. Although RU 486 is classically described as an antiprogestin, agonist actions have been observed in addition to its the well documented antiglucocorticoid effects. All of these variables may contribute to the confounding observations of progesterone and RU 486 action on the ovary. Regardless of these caveats, experimental paradigms have demonstrated that RU 486, either indirectly or directly, regulates ovarian folliculogenesis, stimulates and/or inhibits steroidogenesis depending on the species and time of RU 486 administration, inhibits ovulation, and modulates luteal function. These findings supports a progesterone-dependent mechanism in these varied aspects of ovarian function.
Curry
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University of Kentucky, Lexington 40536, USA.
Nothnick
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WB
D000818:Animals; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology*; D006080:Ovarian Follicle / Q000187:drug effects / Q000254:growth & development; D010053:Ovary / Q000187:drug effects* / Q000502:physiology; D010060:Ovulation / Q000187:drug effects; D011374:Progesterone / Q000502:physiology*; D051381:Rats; D011980:Receptors, Progesterone / Q000187:drug effects / Q000378:metabolism
D006727:Hormone Antagonists; D011980:Receptors, Progesterone; D015735:Mifepristone; D011374:Progesterone