RU 486: a steroid with antiglucocorticosteroid activity that only disinhibits the human pituitary-adrenal system at a specific time of day

Détails

ID Serval
serval:BIB_CBCB20D85D6B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
RU 486: a steroid with antiglucocorticosteroid activity that only disinhibits the human pituitary-adrenal system at a specific time of day
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur(s)
Gaillard  R. C., Riondel  A., Muller  A. F., Herrmann  W., Baulieu  E. E.
ISSN
0027-8424 (Print)
Statut éditorial
Publié
Date de publication
06/1984
Volume
81
Numéro
12
Pages
3879-82
Notes
Journal Article --- Old month value: Jun
Résumé
RU 486 is a synthetic steroid hormone antagonist which acts at the receptor level. It has both intrinsic anti-progesterone and antiglucocorticosteroid properties in animals. We investigated the antiglucocorticosteroid activity in humans by evaluating the pituitary-adrenal response to RU 486 in men and in pregnant and nonpregnant women. In non-pregnant women, RU 486 (approximately equal to 1 mg/kg of body weight per day) produced an interruption of the luteal phase without affecting the pituitary-adrenal axis, thereby indicating a more potent anti-progesterone than antiglucorticosteroid effect. In the course of pregnancy interruption by RU 486 (approximately equal to 4 mg/kg per day), there was a significant increase in plasma corticotropin, beta-lipotropin, and cortisol concentrations. In normal men, RU 486 administration led to a dose-dependent stimulation of plasma corticotropin, beta-endorphin, and cortisol. This disinhibition of the pituitary-adrenal axis was only observed during the morning hours of the circadian rhythm. When administered concomitantly with 1 mg of dexamethasone at midnight, 6 mg of RU 486 per kg completely suppressed the dexamethasone inhibitory effect on the pituitary-adrenal axis. These results indicate that RU 486 is an antiglucocorticosteroid that disrupts the negative pituitary feedback of both the morning cortisol rise and administered dexamethasone. Furthermore, they demonstrate the possibility of optimizing the anti-progestational effect of the compound and its potential use for human fertility control by modifying the dose and the time of administration of the drug and thereby minimizing the antiglucocorticosteroid effect.
Mots-clé
Abortifacient Agents, Steroidal Adrenocorticotropic Hormone/blood *Circadian Rhythm Dexamethasone/*antagonists & inhibitors Endorphins/blood Estrenes/*pharmacology Female Humans Hydrocortisone/blood Male Menstruation/drug effects Mifepristone Pituitary-Adrenal System/*drug effects receptor level, has both intrinsic antiprogesterone and antiglucocorticosteroid properties in animals The antiglucocorticosteroid activity in humans was investigated by evaluating the pituitary-adrenal response to RU 486 in men and in pregnant and nonpregnant women. In nonpregnant women, RU 486 (approximately 1 mg/kg of body weight/day) produced an interrpution of the luteal phase without affecting the pituitary-adrenal axis, thereby indicating a more potent antiprogesterone than antiglucocorticosteroid effect. In the course of pregnancy interruption by RU 486 (approximately 4 mg/kg/day), there was s significant increase in plasma corticotropin, beta-lipotropin, and cortisol concentrations. In normal men, RU 486 administration led to a dose-dependent stimulation of plasma corticotropin, beta-endorphin, and cortisol. This disinhibition of the pituitary-adrenal axis was only observed during the morning hours of the circadian rhythm. When administered concomitantly with 1 mg dexamethasone at midnight, 6 mg of RU 486/kg completely suppressed the dexamethasone inhibitory effect on the pituitary-adrenal axis. These results indicated that RU 486 is an antiglucocorticosteroid that disrupts the negative pituitary feedback of both the morning cortisol rise and administered dexamethasone. Furthermore, they demonstrate the possibility of optimizing the antiprogestational effect of the compound and its potential use for human fertility control by modifying the dose and time of administration of the drug and thereby minimizing the antiglucocorticosteroid effect.
Pubmed
Web of science
Open Access
Oui
Création de la notice
15/02/2008 17:57
Dernière modification de la notice
09/05/2019 1:19
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