ACUTE EFFECTS OF ESTRADIOL INFUSION AND NALOXONE ON LUTEINIZING-HORMONE SECRETION IN PUBERTAL BOYS

We have shown previously in pubertal boys that testosterone (T) suppre sses the nocturnal augmentation of luteinizing hormone (LH) secretion principally by decreasing LH pulse frequency. As T can be aromatised t o estradiol (E-2), and E-2 effects on LH secretory dynamics may be sep arate from those of T, we examined the effects of acute E-2 infusion o n LH secretion in pubertal boys. Opioid receptor blockade has been rep orted to increase LH secretion after estradiol suppression in adult me n, so we also examined whether naloxone might augment LH secretion dur ing E-2 treatment in pubertal boys. Starting at 1000 h, eight pubertal boys were given a 33 h saline infusion, followed 1 week later by an E -2 infusion at 4.6 nmol/m(2)/h. During both infusions, four iv boluses of saline were given hourly beginning at 1200 h on the first day, and four naloxone iv boluses, 0.1 mg/kg each, were given hourly beginning at 1200 h on the second day. Blood was obtained every 15 min for LH, and every 60 min for T and E-2, from 1200 h until the end of the infus ion. Pituitary responsiveness to gonadotropin-releasing hormone (GnRH) was assessed after both infusions by iv administration of 250 ng/kg s ynthetic GnRH. Estradiol infusion increased the mean plasma E-2 concen tration from 23 +/- 4 to 46 +/- 6 pmol/L (P < 0.01) and suppressed mea n plasma T from 4.9 +/- 1.4 to 3.0 +/- 3.5 nmol/L (saline vs. E-2 infu sion, P < 0.05). The overall mean LH was suppressed by E-2 infusion fr om 3.7 +/- 0.5 to 2.2 +/- 0.4 IU/L (saline vs. E-2 infusion, P < 0.01) . LH pulse frequency was suppressed by 50%, whereas mean LH pulse ampl itude was not different between saline and E-2 infusions. Administrati on of naloxone did not alter the mean LH, LH pulse frequency, or ampli tude during either saline or E-2 infusions. Pituitary responsiveness t o exogenous GnRH was similar during both infusions. These studies indi cate that E-2 produces its negative feedback in pubertal boys principa lly by suppression of LH pulse frequency, and naloxone does not revers e these suppressive effects. Thus E-2 suppression of LH secretion is m ediated by a decrease of hypothalamic GnRH secretion that is independe nt of endogenous opioid pathways.