The antiovulatory potential of progesterone antagonists correlates with a down-regulation of progesterone receptors in the hypothalamus, pituitary and ovaries
| Autor: | H. Michna, T. Schulz, Yukishige Dr Nishino, J. Donath |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
medicine.medical_specialty
Gonadotropins Equine media_common.quotation_subject Hypothalamus Down-Regulation Ovary Gonanes Biology Chorionic Gonadotropin Progesterone Antagonist Hormone Antagonists Anterior pituitary Internal medicine Progesterone receptor medicine Animals Rats Wistar Receptor Ovulation Progesterone media_common Estradiol Antagonist General Medicine Immunohistochemistry Rats medicine.anatomical_structure Endocrinology Pituitary Gland Female Anatomy Receptors Progesterone Developmental Biology |
| Zdroj: | Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft. 182(2) |
| ISSN: | 0940-9602 |
| Popis: | Summary These studies analyze the regulation of progesterone receptors (PRs) in central and peripheral tissues with the aim of further understanding mechanistically the inhibition of ovulation by progesterone antagonists (PA). Therefore, it was of interest to investigate the influence of the progesterone receptor antagonist, Onapristone (ON), on PRs in the ovary, pituitary (PT), and hypothalamus (HYP), since ON effectively inhibits ovulation in rats. For this study PMSG/hCG-primed immature and adult female rats were treated with ON. Immunohistochemistry was used for the detection of PRs. Progesterone (P 4 ) and estradiol (E 2 ) levels were determined by RIA. PR expression in the ovaries of immature rats was not detectable until after hCG administration. In these animals, ON caused a reduction in the staining intensity of PR in the tertiary follicles at the time when the preovulatory P 4 -surge was inhibited (6 h post hCG). Adult rats treated for 15 days with ON showed a decreased PR expression in PT and HYP. At this time (proestrus, 7 p.m.) the P 4 and E 2 levels are significantly lowered. These results suggest that after treatment with ON the expression of PR is reduced in the ovary, PT and HYP. The regulation of PR in the ovary seems to be less dependent on estrogens than on LH. Thus, it is conceivable that the reduced PR expression after ON treatment may be a result of decreased LH sensitivity in the ovary. In the pituitary and hypothalamus, PR expression is stimulated by estrogens and progesterone, and therefore the fall in the P 4 and E 2 levels in ON-treated animals may be responsible for the reduced PR expression in PT and HYP, and may contribute to the antiovulatory effect of ON. We therefore conclude that the mechanism of the antiovulatory potency of progesterone antagonists is based on a reduced preovulatory P 4 -production and PR expression in the ovary and also on the down-regulation of PR in the anterior pituitary and hypothalamus. |
| Databáze: | OpenAIRE |
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