Somatostatin receptor subtype 2 knockout mice are refractory to growth hormone-negative feedback on arcuate neurons

Mol Endocrinol. 1997 Oct;11(11):1709-17. doi: 10.1210/mend.11.11.0016.


The pulsatile nature of GH release is apparently regulated by alternating sequential changes in two hypothalamic hormones, GH releasing hormone (GHRH) and somatostatin. Entrainment of this pulsatility appears to involve GH-mediated negative feedback. Recently a new receptor involved in GH release was cloned. Activation of this receptor by GH-releasing peptides and MK-0677 initiates and amplifies GH pulsatility and is associated with increased Fos immunoreactivity and electrical activity in GHRH containing arcuate neurons. We show that pretreating mice with GH blocks activation of these neurons by MK-0677. Similarly, octreotide inhibited the action of MK-0677. To determine whether this GH-mediated negative feedback on GHRH neurons was direct, or by GH stimulation of somatostatin release from periventricular neurons, we selectively inactivated the gene for one of the five specific somatostatin receptor subtypes (subtype 2). In the knockout mice, both GH and octreotide failed to inhibit MK-0677 activation of arcuate neurons. GH did, however, increase Fos immunoreactivity in the periventricular nucleus, consistent with GH stimulation of somatostatin release from periventricular neurons. Thus, GH-mediated negative feedback involves signaling between periventricular and arcuate neurons with the signal being transduced specifically through somatostatin subtype 2 receptors.

MeSH terms

  • Animals
  • Arcuate Nucleus of Hypothalamus / drug effects
  • Arcuate Nucleus of Hypothalamus / metabolism*
  • Feedback
  • Gene Expression Regulation / drug effects
  • Growth Hormone / metabolism*
  • Growth Hormone-Releasing Hormone / pharmacology*
  • Growth Hormone-Releasing Hormone / physiology
  • Hypothalamus, Posterior / drug effects
  • Hypothalamus, Posterior / metabolism
  • Indoles / pharmacology
  • Mice
  • Mice, Knockout
  • Octreotide / pharmacology
  • Proto-Oncogene Proteins c-fos / biosynthesis
  • Proto-Oncogene Proteins c-fos / genetics
  • Receptors, Somatostatin / deficiency
  • Receptors, Somatostatin / drug effects
  • Receptors, Somatostatin / genetics
  • Receptors, Somatostatin / physiology*
  • Secretory Rate / drug effects
  • Secretory Rate / physiology
  • Signal Transduction
  • Somatostatin / pharmacology
  • Somatostatin / physiology*
  • Spiro Compounds / pharmacology


  • Indoles
  • Proto-Oncogene Proteins c-fos
  • Receptors, Somatostatin
  • Spiro Compounds
  • Somatostatin
  • Growth Hormone
  • Growth Hormone-Releasing Hormone
  • somatostatin receptor 2
  • ibutamoren mesylate
  • Octreotide