AJP - Regu Information on EB 2010
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Regul Integr Comp Physiol 282: R753-R764, 2002; doi:10.1152/ajpregu.00407.2001
0363-6119/02 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (36)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Farhy, L. S.
Right arrow Articles by Veldhuis, J. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Farhy, L. S.
Right arrow Articles by Veldhuis, J. D.
Vol. 282, Issue 3, R753-R764, March 2002

Unequal autonegative feedback by GH models the sexual dimorphism in GH secretory dynamics

Leon S. Farhy1, Martin Straume1,2,3, Michael L. Johnson1,2,4, Boris Kovatchev2,5, and Johannes D. Veldhuis1,2,3

1 Division of Endocrinology and Metabolism, Department of Internal Medicine, 5 Departments of Psychiatric Medicine and Health Evaluation Sciences, 4 Department of Pharmacology, The University of Virginia Health System, 2 Center for Biomathematical Technology, and 3 National Science Foundation Center for Biological Timing, University of Virginia, Charlottesville, Virginia 22908

Growth hormone (GH) secretion, controlled principally by a GH-releasing hormone (GHRH) and GH release-inhibiting hormone [somatostatin (SRIF)] displays vivid sexual dimorphism in many species. We hypothesized that relatively small differences within a dynamic core GH network driven by regulatory interactions among GH, GHRH, and SRIF explain the gender contrast. To investigate this notion, we implemented a minimal biomathematical model based on two coupled oscillators: time-delayed reciprocal interactions between GH and GHRH, which endow high-frequency (40-60 min) GH oscillations, and time-lagged bidirectional GH-SRIF interactions, which mediate low-frequency (occurring every 3.3 h) GH volleys. We show that this basic formulation, sufficient to explain GH dynamics in the male rat [Farhy LS, Straume M, Johnson ML, Kovatchev BP, and Veldhuis JD. Am J Physiol Regulatory Integrative Comp Physiol 281: R38-R51, 2001], emulates the female pattern of GH release, if autofeedback of GH on SRIF is relaxed. Relief of GH-stimulated SRIF release damps the slower volleylike oscillator, allowing emergence of the underlying high-frequency oscillations that are sustained by the GH-GHRH interactions. Concurrently, increasing variability of basal somatostatin outflow introduces quantifiable, sex-specific disorderliness of the release process typical of female GH dynamics. Accordingly, modulation of GH autofeedback on SRIF within the interactive GH-GHRH-SRIF ensemble and heightened basal SRIF variability are sufficient to transform the well-ordered, 3.3-h-interval, multiphasic, volleylike male GH pattern into a femalelike profile with irregular pulses of higher frequency.

somatostatin; growth hormone-releasing hormone; hypothalamus; mathematical model; male; female; gender; somatotropic axis


This article has been cited by other articles:


Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
L. S. Farhy, Z. Du, Q. Zeng, P. P. Veldhuis, M. L. Johnson, K. L. Brayman, and A. L. McCall
Amplification of pulsatile glucagon counterregulation by switch-off of {alpha}-cell-suppressing signals in streptozotocin-treated rats
Am J Physiol Endocrinol Metab, September 1, 2008; 295(3): E575 - E585.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
L. S. Farhy, C. Y. Bowers, and J. D. Veldhuis
Model-projected mechanistic bases for sex differences in growth hormone regulation in humans
Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2007; 292(4): R1577 - R1593.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
N. Baccam, G. Alonso, T. Costecalde, P. Fontanaud, F. Molino, I. C. A. F. Robinson, P. Mollard, and P.-F. Mery
Dual-Level Afferent Control of Growth Hormone-Releasing Hormone (GHRH) Neurons in GHRH-Green Fluorescent Protein Transgenic Mice
J. Neurosci., February 14, 2007; 27(7): 1631 - 1641.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
L. S. Farhy and J. D. Veldhuis
Deterministic construct of amplifying actions of ghrelin on pulsatile growth hormone secretion
Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2005; 288(6): R1649 - R1663.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
L. S. Farhy and J. D. Veldhuis
Putative GH pulse renewal: periventricular somatostatinergic control of an arcuate-nuclear somatostatin and GH-releasing hormone oscillator
Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2004; 286(6): R1030 - R1042.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
L. S. Farhy and J. D. Veldhuis
Joint pituitary-hypothalamic and intrahypothalamic autofeedback construct of pulsatile growth hormone secretion
Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2003; 285(5): R1240 - R1249.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online