TY - JOUR
T1 - Age or factors associated with aging attenuate testosterone's concentration-dependent enhancement of the regularity of luteinizing hormone secretion in healthy men
AU - Liu, Peter Y.
AU - Takahashi, Paul Y.
AU - Roebuck, Pamela D.
AU - Veldhuis, Johannes D.
N1 - Funding Information:
This work was supported in part by the National Center for Research Resources (Rockville, MD) Grant M01 RR00585 to the General Clinical Research Center of the Mayo Clinic and Foundation, the National Institutes of Health (Bethesda, MD) Grants RO1 AG23133 and DK60717. P.Y.L. was supported by fellowships from the National Health and Medical Research Council of Australia (Grant 262025) and the American Australian Association. P.Y.T. was supported by a Mayo Institutional Medicine Innovation Development and Advancement System Award.
PY - 2006/10
Y1 - 2006/10
N2 - Background: Healthy older men have reduced testosterone (Te) production and frequent, small irregular LH pulses. Which is cause and which is effect are not known. Rationale: In model systems, frequent and irregular LH pulses reflect attenuated feedback inhibition by Te. Hypothesis: Factors associated with aging impair negative feedback by Te. Subjects and Setting: Healthy men at an academic medical center were studied. Methods: The study used quantification of the regularity of LH release patterns during blockade of gonadal steroidogenesis and graded transdermal Te addback in 18 healthy men aged 18-65 yr. Results: In the cohort as a whole, stepwise Te repletion repressed LH concentrations (P = 0.001) and enhanced the quantifiable orderliness of LH release patterns (P < 0.001). By regression analysis, age attenuated the capability of increasing Te concentrations to regularize LH secretion patterns (P = 0.019). However, after a fixed GnRH stimulus, the effect of Te on LH regularity was invariant of the age factor (P = 0.16), thus pointing to a hypothalamic locus of impaired Te feedback. Summary: Aging disrupts the capability of systemic Te concentrations to maintain orderly LH secretion under endogenous, but not exogenous, GnRH drive. Conclusions: Age or factors associated with increased age reduce negative feedback by any given total Te concentration on hypothalamopituitary GnRH-LH outflow, thus contributing to disorderly LH secretion.
AB - Background: Healthy older men have reduced testosterone (Te) production and frequent, small irregular LH pulses. Which is cause and which is effect are not known. Rationale: In model systems, frequent and irregular LH pulses reflect attenuated feedback inhibition by Te. Hypothesis: Factors associated with aging impair negative feedback by Te. Subjects and Setting: Healthy men at an academic medical center were studied. Methods: The study used quantification of the regularity of LH release patterns during blockade of gonadal steroidogenesis and graded transdermal Te addback in 18 healthy men aged 18-65 yr. Results: In the cohort as a whole, stepwise Te repletion repressed LH concentrations (P = 0.001) and enhanced the quantifiable orderliness of LH release patterns (P < 0.001). By regression analysis, age attenuated the capability of increasing Te concentrations to regularize LH secretion patterns (P = 0.019). However, after a fixed GnRH stimulus, the effect of Te on LH regularity was invariant of the age factor (P = 0.16), thus pointing to a hypothalamic locus of impaired Te feedback. Summary: Aging disrupts the capability of systemic Te concentrations to maintain orderly LH secretion under endogenous, but not exogenous, GnRH drive. Conclusions: Age or factors associated with increased age reduce negative feedback by any given total Te concentration on hypothalamopituitary GnRH-LH outflow, thus contributing to disorderly LH secretion.
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U2 - 10.1210/jc.2005-2811
DO - 10.1210/jc.2005-2811
M3 - Article
C2 - 16868060
AN - SCOPUS:33749561819
SN - 0021-972X
VL - 91
SP - 4077
EP - 4084
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 10
ER -