title: Acute effects of testosterone infusion and naloxone on luteinizing hormone secretion in normal men.
abstract: To evaluate the role of endogenous opioid pathways in the acute suppression of LH secretion by testosterone (T) infusion in men, we studied eight normal healthy volunteers who received a saline infusion, followed 1 week later by a T infusion (960 nmol/h) starting at 1000 h and lasting for 33 h. After 2 h of infusion (both saline and T), four iv boluses of saline were given hourly, and after 26 h of infusion, four hourly iv boluses of naloxone were given. Blood was obtained every 15 min for LH and every 30 min for T. T infusion increased the mean plasma T concentration 2.1-fold (18.7 +/- 2.1 to 39.5 +/- 3.5 nmol/L, saline vs. T infusion, P < 0.01). The mean plasma LH concentration was 7.9 +/- 0.5 IU/L during the saline control study and was decreased to 6.9 +/- 0.6 IU/L by the infusion of T (P < 0.05). LH pulse frequency was similar during both saline and T infusions (0.48 +/- 0.02 vs. 0.43 +/- 0.04 pulses/man.h, saline vs. T infusion). The mean LH pulse amplitude decreased from 4.3 +/- 0.4 IU/L during saline infusion to 3.3 +/- 0.2 IU/L during T infusion (P < 0.05). The administration of naloxone increased the mean plasma LH concentration significantly during saline infusion (7.6 +/- 0.4 to 10.0 +/- 0.9 IU/L, saline vs. naloxone boluses, P < 0.01), but not during T infusion (6.9 +/- 0.6 vs. 7.3 +/- 0.6 IU/L). LH pulse frequency increased significantly after the administration of naloxone during both saline and T infusions (0.54 +/- 0.04 to 0.71 +/- 0.08 pulses/man.h, saline vs. naloxone boluses during saline infusion, and 0.46 +/- 0.08 to 0.60 +/- 0.07 pulses/man.h during T infusion; P < 0.05). LH pulse amplitude was suppressed by T infusion, but administration of naloxone did not reverse this suppression. The mean amplitude of the LH response to exogenous GnRH (250 ng/kg) was decreased by T infusion from 48 +/- 13.5 to 31.2 +/- 8.5 IU/L (P < 0.01). Therefore, in men, the administration of naloxone increases LH pulse frequency during both saline and T infusions, but the acute suppression of LH pulse amplitude seen with T infusion was not reversed by naloxone. This pattern contrasts sharply with the effects of T infusion in pubertal boys, as elucidated by our earlier studies. The negative feedback effects of T on LH secretion are primarily hypothalamic in early pubertal boys and change to pituitary suppression in men.
authors.affiliation: Department of Pediatrics, University of Michigan, Ann Arbor 48109-0718.
authors.forename: G B
authors.initials: GB
authors.lastname: Kletter
authors.forename: C M
authors.initials: CM
authors.lastname: Foster
authors.forename: I Z
authors.initials: IZ
authors.lastname: Beitins
authors.forename: J C
authors.initials: JC
authors.lastname: Marshall
authors.forename: R P
authors.initials: RP
authors.lastname: Kelch
mesh_terms: D000328:Adult; D004958:Estradiol / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D006801:Humans; D007262:Infusions, Intravenous; D007986:Luteinizing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D010902:Pituitary Gland / Q000187:drug effects; D012016:Reference Values; D013739:Testosterone / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D007987:Gonadotropin-Releasing Hormone; D009270:Naloxone; D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone