(note Leydig cell aging changes can be blocked by testosterone
supplementation - Proc Natl Acad Sci USA 96(26): 14877-14881 Dec 21,1999)
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From: pekka <ppekkaNOppSPAM@hotmail.com.invalid>
Newsgroups: misc.fitness.weights
Eur J Endocrinol 1999 Sep;141(3):257-66
Two-week pulsatile gonadotropin releasing hormone infusion
unmasks dual (hypothalamic and Leydig cell) defects in the
healthy aging male gonadotropic axis.
Mulligan T, Iranmanesh A, Kerzner R, Demers LW, Veldhuis JD
McGuire VA Medical Center, Richmond, Virginia, USA.
Mulligan.Thomas_M@Richmond.VA.GOV
OBJECTIVE: To examine the possibility that lower serum
bioavailable testosterone concentrations, without increased LH
release, in healthy older men, reflects hypothalamic GnRH
deficiency. DESIGN: We used a randomized, double-blind, placebo-
controlled design. METHODS: We treated each of five young (ages
20-34 years) and five older (ages 60-78 years) men with 2 weeks
of randomized infusions of saline or pulsatile GnRH (100 ng/kg
i.v. every 90 min). RESULTS: At baseline (saline infusion),
older men had more LH pulses (young compared with old, 10 +/-
0.6 compared with 15 +/- 1, P = 0.0026) per 24h, reduced
fractional LH pulse amplitude (219 +/- 17% compared with 167 +/-
40%, P = 0.0376), and more disorderly hormone release as judged
by approximate entropy (ApEn) (LH, P < or = 0.0001;
testosterone, P < or = 0.0047). In response to pulsatile i.v.
GnRH infusions, serum 24-h LH concentrations (measured by
immunoradiometric assay (IRMA)), increased equivalently in young
and older men (to 7.3 +/- 1.2 and 7.2 +/- 1.8 IU/l
respectively). GnRH treatment also normalized LH pulse frequency
and amplitude, ApEn, and plasma biologically active LH (pooled)
concentrations. In contrast, 24-h testosterone concentrations
failed to increase equivalently in older men (young compared
with old, 869 +/- 88 compared with 517 +/- 38 ng/dl, P =
0.0061), reflecting lower testosterone peak maxima (995 +/- 108
compared with 583 +/- 48 ng/dl, P = 0.0083) and interpeak nadirs
(750 +/- 87 compared with 427 +/- 26 ng/dl, P = 0.0073).
CONCLUSIONS: We have demonstrated that, in older men, successful
reconstitution of 24-h pituitary (bioactive) LH output and
pulsatile (IRMA) LH release patterns could be achieved by a
fixed exogenous GnRH pulse signal, thereby implicating altered
endogenous hypothalamic GnRH release in the relative
hypogonadotropism of aging. The failure of testosterone
concentrations to increase concomitantly points to a
simultaneous Leydig cell defect. We conclude that aging in men
is marked by a dual defect in the central nervous system-
pituitary-Leydig cell axis.
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