Nocturnal naloxone fails to reverse the suppressive effects of testosterone infusion on luteinizing hormone secretion in pubertal boys.
LH secretion is maximal during the night in pubertal boys, and testosterone (T) administration blunts this nocturnal rise of LH. We have previously shown that in pubertal boys, the acute negative feedback effects of T infusion on LH secretion during the daytime cannot be reversed by opioid receptor blockade. To determine whether the nocturnal secretion of LH in early puberty is regulated by endogenous opioid pathways, we determined whether naloxone during the night affected LH secretion or T-mediated suppression of LH secretion. Seven pubertal boys (bone age, 11-13.5 yr) were given a control infusion of saline, followed 1 week later by an infusion of T at 960 nmol/m2.h for 41 h starting at 2000 h. During both saline and T infusions, six iv boluses of saline were given hourly beginning at 2400 h on the first day, and six iv boluses of naloxone (0.1 mg/kg each) were given hourly beginning at 2400 h on the second day. Starting at 2200 h, blood was obtained every 15 min for LH and every 30 min for T determinations for 14 h each night. Pituitary responsiveness was assessed at the end of each study night by i.v. bolus administration of 250 ng/kg synthetic GnRH. T infusion increased the mean T concentration 6-fold (P < 0.0001) and suppressed the mean plasma LH concentrations from 5.6 +/- 0.6 to 3.8 +/- 0.6 IU/L (P < 0.01). The nocturnal augmentation of LH secretion was suppressed by the infusion of T, and this suppression was not reversed by naloxone. The mean nighttime plasma LH (2400-0600 h) was 8.1 +/- 1.1 IU/L during the control saline infusion and 5.1 +/- 0.6 IU/L during the T infusion (P < 0.01). The mean LH level was 4.0 +/- 0.7 IU/L during the administration of naloxone boluses concomitantly with the T infusion, not significantly different from that during the T infusion. Likewise, LH pulse frequency during the same time period was decreased by T infusion from 0.6 +/- 0.1 to 0.36 +/- 0.04 pulses/boy.h (P < 0.05), and it was unaltered by coadministration of naloxone (0.38 +/- 0.12 pulses/boy.h). Naloxone administration during the saline infusion did not increase either the mean plasma LH concentration (7.5 +/- 0.7 IU/L; P = NS vs. saline control) or the LH pulse frequency (0.69 +/- 0.1 pulses/boy.h; P = NS vs. saline control). Pituitary responsiveness to GnRH was similar on each of the 4 nights during either saline or T infusions.(ABSTRACT TRUNCATED AT 400 WORDS)
Kletter
G B
GB
Department of Pediatrics, University of Michigan, Ann Arbor 48109.
Foster
C M
CM
Brown
M B
MB
Beitins
I Z
IZ
Marshall
J C
JC
Kelch
R P
RP
D000293:Adolescent; D002940:Circadian Rhythm; D004334:Drug Administration Schedule; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D006801:Humans; D007986:Luteinizing Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D009270:Naloxone / Q000008:administration & dosage* / Q000494:pharmacology; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011627:Puberty / Q000502:physiology*; D011673:Pulsatile Flow; D012965:Sodium Chloride / Q000494:pharmacology; D013739:Testosterone / Q000494:pharmacology*
D009270:Naloxone; D013739:Testosterone; D012965:Sodium Chloride; D007986:Luteinizing Hormone; D013007:Growth Hormone-Releasing Hormone