Changes in the Responsiveness of Luteinizing Hormone Secretion to Infusion of the Opioid Antagonist Naloxone Throughout Male Sexual Maturation

Clin Endocrinol (Oxf). 1988 Jul;29(1):17-28. doi: 10.1111/j.1365-2265.1988.tb00245.x.


The present study investigated the time of male sexual maturation during which hypothalamic inhibitory opioid activity can be detected. Normal prepubertal (Tanner stage G 1 (Ts-G1) (n = 4], early pubertal (Ts-G2 (n = 5], pubertal (Ts-G3 (n = 4), and Ts-G4 (n = 2] and adult subjects (Ts-G5 (n = 4] receives a rapid infusion of the selective opiate antagonist nalocone (NAL) (20 mg over 10 min). LH secretion was assessed by frequent (every 10 min for 2 h) venous sampling before and after administration of the opiate blocker, as well as by the LH response to exogenous GnRH. All but one (a Ts-G2 subject) pubertal boys showed aprompt and sustained increase in serum LH concentrations after NAL administration, as disclosed by the areas under the LH curve (aLHc) calculated from samples obtained before and after NAL infusion (aLHc in four Ts-G2 responders, 162 +/- 20 (mean +/- SEM) vs 314 +/- 56 mIU/ml/min before and after NAL respectively, P less than 0.025; Ts-G3, 227 +/- 35 vs 362 +/- 56 mIU/ml/min, P less than 0.025; Ts-G4 and Ts-G5, 432 +/- 77 vs 687 +/- 91 mIU/ml/min, P less than 0.05). In contrast, none of the prepubertal children had significant changes in LH secretion after the NAL challenge (154 +/- 17 vs 154 +/- 9 mIU/ml/min). Although all NAL responders exhibited serum testosterone (T) levels above 5 nmol/l, a positive correlation between individual T values and magnitude of LH responses to NAL was not found. All subjects had significant serum LH increments after GnRH administration. In a second series of studies, additional groups of Ts-G1 subjects were primed during 5 days either with GnRH alone or with GnRH plus sex steroids (ethinyl oestradiol 12.5 micrograms/12 h or testosterone enanthate 1.8 mg/kg body weight (single dose], before NAL administration, to investigate whether hypothalamic opioid activity might be unmasked by additional sex steroids. None of the priming schemes significantly modified the pituitary LH responses to NAL infusion (GnRH-primed group, 145 +/- 48 vs 139 +/- 43 mIU/ml/min before and after NAL, respectively; GnRH plus ethinyl oestradiol-primed group, 124 +/- 42 vs 107 +/- 34 mIU/ml/min; GnRH plus testosterone enanthate-primed group, 64 +/- 10 vs 57 +/- 24 mIU/ml/min). This study suggests that the development and/or maturation of the opioid control of LH secretion is temporally related with the onset of puberty.(ABSTRACT TRUNCATED AT 400 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Ethinyl Estradiol / pharmacology
  • Humans
  • Luteinizing Hormone / metabolism*
  • Male
  • Naloxone / pharmacology*
  • Pituitary Gland / drug effects
  • Pituitary Hormone-Releasing Hormones / pharmacology
  • Sexual Maturation*
  • Testosterone / analogs & derivatives
  • Testosterone / pharmacology


  • Pituitary Hormone-Releasing Hormones
  • Naloxone
  • Testosterone
  • Ethinyl Estradiol
  • testosterone enanthate
  • Luteinizing Hormone