TY - JOUR
T1 - Hypothesis testing of the aging male gonadal axis via a biomathematical construct
AU - Keenan, Daniel M.
AU - Veldhuis, Johannes D.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - Neuroendocrine axes are feedback- and feedforward-coupled dynamic ensembles. Disruption of selected pathways in such networklike organizations may explicate loss of orderly hormonal output as observed in aging. To test this notion more explicitly, we implemented an earlier computer-assisted biomathematical model of the interlinked male hypothalamo [gonadotropin-releasing hormone (GnRH)]-pituitary [luteinizing hormone, (LH)]-testicular [Leydig cell testosterone (Te)] axis (Am J Physiol Endocrinol Metab Physiol 275: E157-E176, 1988; Keenan D., W. Sun, and J. D. Veldhuis, SIAM J Appl Math 61: 934-965, 2000). Thereby, we appraise mechanistic hypotheses for more disorderly LH and Te secretion in aging men. We compare model predictions with monitored abnormalities in the older male, namely, irregular patterns of individual and synchronous LH and Te release, reduced 24-h rhythmic Te output, and variably elevated LH secretion. Among the mechanisms examined, the most parsimonious aging hypothesis would entail impaired LH feedforward on Te without or with attenuated Te feedback on GnRH/LH secretion. This investigative strategy should aid in exploring new postulates of disrupted feedback networks in pathophysiology.
AB - Neuroendocrine axes are feedback- and feedforward-coupled dynamic ensembles. Disruption of selected pathways in such networklike organizations may explicate loss of orderly hormonal output as observed in aging. To test this notion more explicitly, we implemented an earlier computer-assisted biomathematical model of the interlinked male hypothalamo [gonadotropin-releasing hormone (GnRH)]-pituitary [luteinizing hormone, (LH)]-testicular [Leydig cell testosterone (Te)] axis (Am J Physiol Endocrinol Metab Physiol 275: E157-E176, 1988; Keenan D., W. Sun, and J. D. Veldhuis, SIAM J Appl Math 61: 934-965, 2000). Thereby, we appraise mechanistic hypotheses for more disorderly LH and Te secretion in aging men. We compare model predictions with monitored abnormalities in the older male, namely, irregular patterns of individual and synchronous LH and Te release, reduced 24-h rhythmic Te output, and variably elevated LH secretion. Among the mechanisms examined, the most parsimonious aging hypothesis would entail impaired LH feedforward on Te without or with attenuated Te feedback on GnRH/LH secretion. This investigative strategy should aid in exploring new postulates of disrupted feedback networks in pathophysiology.
KW - Gonadotropin-releasing hormone
KW - Leydig cell testosterone
KW - Luteinizing hormone
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U2 - 10.1152/ajpregu.2001.280.6.r1755
DO - 10.1152/ajpregu.2001.280.6.r1755
M3 - Article
C2 - 11353681
AN - SCOPUS:0034968016
SN - 0363-6119
VL - 280
SP - R1755-R1771
JO - American Journal of Physiology
JF - American Journal of Physiology
IS - 6 49-6
ER -