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

Leon S. Farhy, Martin Straume, Michael L. Johnson, Boris Kovatchev, Johannes D. Veldhuis

Research output: Contribution to journalArticlepeer-review

49 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)R753-R764
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number3 51-3
StatePublished - 2002


  • Female
  • Gender
  • Growth hormone-releasing hormone
  • Hypothalamus
  • Male
  • Mathematical model
  • Somatostatin
  • Somatotropic axis

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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