Pathophysiology of the Neuroregulation of Growth Hormone Secretion in Experimental Animals and the Human*
Abstract
During the last decade, the GH axis has become the compelling focus of remarkably active and broad-ranging basic and clinical research. Molecular and genetic models, the discovery of human GHRH and its receptor, the cloning of the GHRP receptor, and the clinical availability of recombinant GH and IGF-I have allowed surprisingly rapid advances in our knowledge of the neuroregulation of the GH-IGF-I axis in many pathophysiological contexts. The complexity of the GHRH/somatostatin-GH-IGF-I axis thus commends itself to more formalized modeling (154, 155), since the multivalent feedback-control activities are difficult to assimilate fully on an intuitive scale. Understanding the dynamic neuroendocrine mechanisms that direct the pulsatile secretion of this fundamental growth-promoting and metabolic hormone remains a critical goal, the realization of which is challenged by the exponentially accumulating matrix of experimental and clinical data in this arena. To the above end, we review here the pathophysiology of the GHRH somatostatin-GH-IGF-I feedback axis consisting of corresponding key neurotransmitters, neuromodulators, and metabolic effectors, and their cloned receptors and signaling pathways. We propose that this system is best viewed as a multivalent feedback network that is exquisitely sensitive to an array of neuroregulators and environmental stressors and genetic restraints. Feedback and feedforward mechanisms acting within the intact somatotropic axis mediate homeostatic…
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GHRH, SS, and ghrelin constitute a minimal set of regulators to pituitary somatotropes.
“The idea is that GHRH, SS, and ghrelin constitute a minimal set of regulators to pituitary somatotropes.”
From Determinants of dual secretagogue drive of burst-like growth hormone secretion in premenopausal women studied under a selective estradiol clamp (2005) · cites this paper as [1]
L-arginine inhibits SS release in the experimental animal and inferentially in the human.
“although l-arginine inhibits SS release in the experimental animal and inferentially in the human (1)”
From Determinants of dual secretagogue drive of burst-like growth hormone secretion in premenopausal women studied under a selective estradiol clamp (2005) · cites this paper as [1]
E2 is not a primary determinant of nonpulsatile GH secretion in the human.
“Equivalent basal GH secretion in a low and high E 2 milieu indicates that E 2 is not a primary determinant of nonpulsatile GH secretion in the human (1,39).”
From Determinants of dual secretagogue drive of burst-like growth hormone secretion in premenopausal women studied under a selective estradiol clamp (2005) · cites this paper as [1]
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Ben-Shlomo, A., & Melmed, S. (2017) · The Pituitary · doi:10.1016/b978-0-12-804169-7.00002-7 · Cited by 11 · see citing works
- Authors
- Giustina, A., & Veldhuis, J. D.
- Affiliations
- University of Brescia (IT)
- University of Virginia (US)
- Venue
- Endocrine Reviews
- Publisher
- The Endocrine Society
- Published
- 1998-12-01
- Volume
- 19
- Issue
- 6
- Pages
- 717-797
- ISSN
- 0163-769X (ISSN-L)
- 1945-7189
- OpenAlex
- W2002748611
- Cited by
- 1,253
- References
- 26
- Citations by year
- 2026: 6 · 2025: 16 · 2024: 25 · 2023: 29 · 2022: 29 · 2021: 30 · 2020: 31 · 2019: 35 · 2018: 39 · 2017: 29 · 2016: 30 · 2015: 47 · 2014: 43 · 2013: 43 · 2012: 37
- FWCI
- 9.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrine Reviews (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Funders
- National Institutes of Health (1r03ag014873-01)
- National Institute on Aging (R01 AG 147991, R03-AG148-73)
- National Center for Research Resources (RR 00847, M01RR000847)
- 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
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Keywords
- growth hormone secretion, neuroendocrine regulation, growth hormone-releasing hormone, somatostatin, insulin-like growth factor I, somatotropic axis, pulsatile hormone secretion, feedback control, growth hormone receptor
- MeSH terms
- Animals, Disease Models, Animal, Humans, Hypothalamic Diseases, Pituitary Diseases, Growth Hormone, Receptors, Neurotransmitter
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