title: Testosterone infusion reduces nocturnal luteinizing hormone pulse frequency in pubertal boys.
abstract: Administration of testosterone (T) can inhibit LH secretion in early pubertal boys. However, the GnRH pulse generator is relatively resistant to the effects of T, since T infusion beginning at 2100 h, 3 h before the usual nighttime increase in T, does not suppress the characteristic increase in LH pulse frequency or amplitude associated with the onset of sleep in early pubertal boys. To test the hypothesis that the hypothalamic-pituitary axis must be exposed to T for a longer duration to suppress the nocturnal rise in LH pulse frequency and amplitude, we infused saline or T at one third the adult male production rate (320 nmol/h), beginning at 1200 h on two consecutive weekends in each of eight early to midpubertal boys. Blood was obtained from 2000-0800 h every 10 min for LH and every 30 min for T measurements. T infusion increased the mean plasma T concentration from 6.9 +/- 1.7 to 11.8 +/- 1.4 nmol/L (P less than 0.01) between 2000-0800 h. Despite the T infusion, the nocturnal rise in mean LH concentration and LH pulse frequency persisted, suggesting that the nocturnal amplification of LH, and by inference GnRH, secretion is resistant to the negative feedback effects of T. A higher dose of T, approximating the adult male production rate (960 nmol/h), was given to eight additional boys beginning at 1200 h. The mean T concentration increased from 4.2 +/- 1.7 to 20.8 +/- 3.1 (P less than 0.001) nmol/L between 2000-0800 h. The mean plasma LH concentration was suppressed by T infusion from 5.2 +/- 0.5 to 2.9 +/- 0.4 IU/L, and LH pulse frequency decreased from 0.50 +/- 0.04 to 0.27 +/- 0.11 pulses/boy/h (P less than 0.01). There was no nocturnal amplification of LH secretion, but high amplitude LH pulses did occur during the night in six of the eight boys. The low dose T infusion had no effect on pituitary LH release by exogenous GnRH. With the high dose T infusion, however, the ability of GnRH, at 25 ng/kg but not at 250 ng/kg, to release pituitary LH was amplified. Thus, T supplementation at one third the adult male production rate does not blunt the sleep-associated nighttime rise in LH pulse frequency or LH concentration. T infusion approximating the adult male production rate suppresses the nocturnal increase in LH pulse frequency and mean LH concentration, and high amplitude, slow frequency LH pulses similar to patterns seen in adult men persist.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Pediatrics, University of Michigan Medical School, Ann Arbor 48109.
authors.forename: C M
authors.initials: CM
authors.lastname: Foster
authors.forename: J M
authors.initials: JM
authors.lastname: Hassing
authors.forename: T M
authors.initials: TM
authors.lastname: Mendes
authors.forename: P M
authors.initials: PM
authors.lastname: Hale
authors.forename: V
authors.initials: V
authors.lastname: Padmanabhan
authors.forename: N J
authors.initials: NJ
authors.lastname: Hopwood
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: D000293:Adolescent; D002940:Circadian Rhythm / Q000187:drug effects*; D007987:Gonadotropin-Releasing Hormone; D006801:Humans; D007262:Infusions, Intravenous; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D008297:Male; D011628:Puberty, Delayed / Q000097:blood / Q000503:physiopathology*; D013739:Testosterone / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone