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Acute Effects of Estradiol Infusion and Naloxone on Luteinizing Hormone Secretion in Pubertal Boys¹

Department of Pediatrics (G.B.K., V.P., I.Z.B., R.P.K., C.M.F.) of the University of Michigan, Ann Arbor, Michigan 48105; Department of Medicine (J.C.M.), University of Virginia Health Sciences Center, Charlottsville, Virginia 22908

Address all correspondence and requests for reprints to: Gad B. Kletter, M.D., Division of Pediatric Endocrinology, Children’s Hospital of Seattle, P.O. Box 5371, Mail Stop CH-92, 4800 Sand Point Way, Seattle, Washington 98105-5371.

We have shown previously in pubertal boys that testosterone (T) suppresses the nocturnal augmentation of luteinizing hormone (LH) secretion principally by decreasing LH pulse frequency. As T can be aromatised to estradiol (E₂), and E₂ effects on LH secretory dynamics may be separate from those of T, we examined the effects of acute E₂ infusion on LH secretion in pubertal boys. Opioid receptor blockade has been reported to increase LH secretion after estradiol suppression in adult men, so we also examined whether naloxone might augment LH secretion during E₂ treatment in pubertal boys. Starting at 1000 h, eight pubertal boys were given a 33 h saline infusion, followed 1 week later by an E₂ infusion at 4.6 nmol/m²/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 E₂, from 1200 h until the end of the infusion. Pituitary responsiveness to gonadotropin-releasing hormone (GnRH) was assessed after both infusions by iv administration of 250 ng/kg synthetic GnRH. Estradiol infusion increased the mean plasma E₂ concentration from 23 ± 4 to 46 ± 6 pmol/L (P < 0.01) and suppressed mean plasma T from 4.9 ± 1.4 to 3.0 ± 3.5 nmol/L (saline vs. E₂ infusion, P < 0.05). The overall mean LH was suppressed by E₂ infusion from 3.7 ± 0.5 to 2.2 ± 0.4 IU/L (saline vs. E₂ infusion, P < 0.01). LH pulse frequency was suppressed by 50%, whereas mean LH pulse amplitude was not different between saline and E₂ infusions. Administration of naloxone did not alter the mean LH, LH pulse frequency, or amplitude during either saline or E₂ infusions. Pituitary responsiveness to exogenous GnRH was similar during both infusions. These studies indicate that E₂ produces its negative feedback in pubertal boys principally by suppression of LH pulse frequency, and naloxone does not reverse these suppressive effects. Thus E₂ suppression of LH secretion is mediated by a decrease of hypothalamic GnRH secretion that is independent of endogenous opioid pathways.

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