Hypothesis testing of the aging male gonadal axis via a biomathematical construct

Daniel M. Keenan, Johannes D Veldhuis

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume280
Issue number6 49-6
StatePublished - 2001
Externally publishedYes

Fingerprint

Luteinizing Hormone
Testosterone
Gonadotropin-Releasing Hormone
Pituitary Hormones
Leydig Cells

Keywords

  • Gonadotropin-releasing hormone
  • Leydig cell testosterone
  • Luteinizing hormone

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Hypothesis testing of the aging male gonadal axis via a biomathematical construct. / Keenan, Daniel M.; Veldhuis, Johannes D.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 280, No. 6 49-6, 2001.

Research output: Contribution to journalArticle

@article{28452c320c44469185c156c5c471b7f4,
title = "Hypothesis testing of the aging male gonadal axis via a biomathematical construct",
abstract = "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.",
keywords = "Gonadotropin-releasing hormone, Leydig cell testosterone, Luteinizing hormone",
author = "Keenan, {Daniel M.} and Veldhuis, {Johannes D}",
year = "2001",
language = "English (US)",
volume = "280",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "6 49-6",

}

TY - JOUR

T1 - Hypothesis testing of the aging male gonadal axis via a biomathematical construct

AU - Keenan, Daniel M.

AU - Veldhuis, Johannes D

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

UR - http://www.scopus.com/inward/record.url?scp=0034968016&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034968016&partnerID=8YFLogxK

M3 - Article

C2 - 11353681

AN - SCOPUS:0034968016

VL - 280

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 6 49-6

ER -