CONICET | Buscador de Institutos y Recursos Humanos

The administration of mifepristone to cycling rats at the day of proestrus induces hypersecretion of prolactin at the following oestrus. We aimed to assess if this effect is due to the antiprogesterone or antiglucocorticoid action of mifepristone, and to help underscore the nature of the circulating hormone/s regulating prolactin secretion at oestrus. Female cycling rats in proestrus were treated with vehicle; the progesterone receptor and glucorticoid receptor antagonists, mifepristone (5 mg/kg) or ORG-33628 (5 mg/kg); the glucocorticoid receptor agonist dexamethasone (27 mg/kg) +/- mifepristone; or the inhibitor of steroid synthesis aminoglutethimide (150mg/kg) +/- mifepristone. The animals were blood-sampled the same day of the treatment at 18.00 h, and at 18.00 h of the following day (oestrus) to assess for prolactin and progesterone levels in circulation. To distinguish antiglucocorticoid from antiprogesterone effects of mifepristone we administered a highly specific neutralizing antibody against progesterone.None of the antagonists modified serum prolactin values at proestrus, but increased prolactin levels at oestrus. Dexamethasone decreased the secretion of prolactin at proestrus, yet the effect was entirely blocked by mifepristone. Furthermore, dexamethasone given at proestrus decreases the secretion of prolactin at oestrus in a mifepristone-reversible manner, suggesting that adrenal corticoids during proestrous may regulate prolactin secretion at oestrus. Inhibition of steroid synthesis with aminoglutethimide led to increased prolactin secretion at oestrus, whereas its association with mifepristone produced an even higher response. Finally, prolactin concentration at oestrus was not modified by the antiprogesterone antibody suggesting that the effect of mifepristone on prolactin secretion is consequence of its antiglucocorticoid effect and not due to its antiprogesterone properties. In conclusion, prolactin secretion in the afternoon of the oestrous day is most likely regulated by glucocorticoids through an inhibitory action.