Evidence against the involvement of opiate neurons in mediating the effect of clomiphene citrate on gonadotropin-releasing hormone neurons

This study was designed to assess whether the hypothalamic action of clomiphene citrate (CC) on gonadotropin-releasing hormone (GnRH) neurons required activity of opiate neurons. Ten women were studied in two successive cycles. In the first cycle they received infusion of saline or naloxone (2 mg intravenous bolus followed by 1.6 mg/hour) for 9 hours, in random order on days 5 and 6 of the cycle. In the second cycle each women was treated with CC (100 mg) for 5 days before study on day 6. In each study, blood samples were collected at 15-minute intervals for 9 hours; during the last hour 10 μg GnRH was given to test the pituitary response. After CC, luteinizing hormone (LH) pulse frequency was accelerated, and mean serum LH, serum follicle-stimulating hormone, and estradiol increased, but the pituitary response to GnRH was unchanged. These changes are best explained by an increase in activity of GnRH neurons. Conversely, naloxone had no effect on LH pulsatility or the pituitary response to GnRH. This indicates that the action of CC at least during the early follicular phase is exerted primarily at the levels of the hypothalamic GnRH pulse generator and does not depend on the activity of opiate neurons.