Somatostatin receptor subtype 2 knockout mice are refractory to growth hormone-negative feedback on arcuate neurons.
Open accessAbstract
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.
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- Authors
- Zheng, H., Bailey, A., Jiang, M.-H., Honda, K., Chen, H. Y., Trumbauer, M. E., Van der Ploeg, L. H. T., Schaeffer, J. M., Leng, G., & Smith, R. G.
- Affiliations
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- University of Edinburgh (GB)
- Venue
- Molecular Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1997-10
- Volume
- 11
- Issue
- 11
- Pages
- 1709-1717
- ISSN
- 0888-8809 (ISSN-L)
- 1944-9917
- OpenAlex
- W2036239129
- Semantic Scholar
- a3cb0d5444d5295da89c93a95ccdf0ac5396679b
- Cited by
- 169
- References
- 35
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 2 · 2022: 1 · 2021: 1 · 2019: 4 · 2018: 3 · 2017: 1 · 2016: 3 · 2015: 1 · 2014: 6 · 2013: 3 · 2012: 4
- FWCI
- 6.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- somatostatin receptor 2, growth hormone-releasing hormone, pulsatile growth hormone secretion, octreotide, Fos-like immunoreactivity, hypothalamic regulation of growth hormone, knockout mice
- MeSH terms
- Animals, Arcuate Nucleus of Hypothalamus, Feedback, Gene Expression Regulation, Hypothalamus, Posterior, Indoles, Secretory Rate, Somatostatin, Growth Hormone, Growth Hormone-Releasing Hormone, Spiro Compounds, Octreotide, Signal Transduction, Proto-Oncogene Proteins c-fos, Receptors, Somatostatin, Mice, Knockout, Mice
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