Effects of dexamethasone and dexamethasone plus naltrexone on pituitary response to GnRH and TRH in normal women

The hypothesis that glucocorticoids have a direct central inhibitory effect on the reproductive axis is sutained by the identification of glucocortico id receptors on GnRH-secreting neurons and gonadotropic pituitary cells. It has been proposed that glucocorticoids and opioids interact centrally in t he regulation of the GnRH-LH axis. The inhibitory effect of glucocorticoids may manifest not only directly through the hormone-receptor link, but also indirectly through an increase in opioid tone. The aim of this study was t o evaluate the role of glucocorticoids a nd glucocorticoids combined with a n opioid antagonist, in the regulation of basal and GnRH- and TRH-stimulate d secretion of LH, FSH and Prl in 7 women with normal menstrual cycles. Blo od samples were obtained every 10 min for an hour. GnRH (50 mu g) and TRH ( 200 mu g) were administered and blood sampling was continued every 15 min f or 2 h (day 1). At 5 a.m. the next day, naltrexone (50 mg) was given and at 8 a.m. the GnRH-TRH test was repeated (day 2). At 5 a.m. on day 3, the pat ients took 2 mg oral dexamethasone and the test was repeated. At 5 a.m. on day 4, the patients took naltrexone and dexamethasone and at 8 a.m. the GnR H-TRH test was repeated. Administration of naltrexone did not cause signifi cant changes in basal concentrations of LH and FSH and their response to Gn RH. The area under the curve of the LH response to GnRH on day 3 was signif icantly less than an clays 1, 2 and 4. Administration of naltrexone (day 2) did not cause any significant increase in basal and TRH-stimulated levels of Prl with respect to day 1. On day 3, dexamethasone caused a reduced resp onse of Prl to TRH. Pretreatment: with naltrexone (day 4) prevented this re duction. These results suggest that suppression of the response of LH to Gn RH induced by dexamethasone may be partly mediated by endogenous opioids. D examethasone led to a reduction in the response of Prl to TRH, and naltrexo ne blocked this suppression. Hence the suppression of Prl and LH by dexamet hasone must be partly mediated by endogenous opioids, which must therefore inhibit pituitary secretion of Prl.