Regulation of the pituitary somatotroph cell by GHRH and its receptor

Kelly Edward Mayo*, T. Miller, V. DeAlmeida, P. Godfrey, Jing Zheng, S. R. Cunha, G. Cutler, C. Carter-Su, L. Frohman

*Corresponding author for this work

Research output: Contribution to journalArticle

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Abstract

Hormones from the hypothalamus mediate interactions between the nervous and endocrine systems by controlling the activity of specific target cells in the anterior pituitary gland. The hypothalamic peptide, growth hormone-releasing hormone (GHRH), acts on pituitary somatotroph cells to stimulate their proliferation during development and to regulate their ability to produce and secrete growth hormone (GH). These actions are mediated by a recently identified receptor for GHRH that belongs to family B-Ill of the G protein-coupled receptor superfamily. The rat GHRH receptor is expressed predominantly in the pituitary gland and in somatotroph cells. To investigate this tissue- and cell-specific expression, the receptor gene has been cloned and characterized. The receptor gene promoter is selectively expressed in pituitary cells and is regulated by the pituitary-specific transcription factor Pit-1. There is a sexual dimorphism in GHRH receptor expression in the rat pituitary, suggesting regulation by gonadal steroids. In addition, glucocorticoids are potent positive regulators of GHRH receptor gene expression. Substantial evidence points to an important role for GHRH in regulating the proliferation and functional activity of the somatotroph cell. This is best observed in the dwarf little mouse, which harbors a mutation in the extracellular domain of the GHRH receptor that abolishes the receptor's hormone-binding and signaling properties, resulting in severe somatotroph hypoplasia. Complementary studies in transgenic mice overexpressing the ligand GHRH reveal corresponding somatotroph hyperplasia. Consistent with these observations, GHRH potently activates the MAP kinase pathway in pituitary somatotroph cells. To better understand the hormone-binding and signaling properties of the GHRH receptor, mutant and chimeric receptors have been analyzed to define domains important for GHRH interaction. The GHRH receptor signals predominantly through cAMP-dependent pathways; however, a variant form of the GHRH receptor with an insertion into the third intracellular domain, generated through alternative RNA processing, binds GHRH but fails to signal, suggesting potential modulation of receptor function at a post-transcriptional level. This chapter will integrate these basic investigations of GHRH and its receptor with current information on the involvement of the GHRH signaling system in human diseases of GH secretion and growth.

Original languageEnglish (US)
Pages (from-to)237-267
Number of pages31
JournalRecent Progress in Hormone Research
Volume55
StatePublished - Dec 1 2000

Fingerprint

Somatotrophs
Growth Hormone-Releasing Hormone
Hormones
Transcription Factor Pit-1
Gene Expression
somatotropin releasing hormone receptor
Endocrine System
Anterior Pituitary Gland
Human Growth Hormone
Peptide Hormones
Pituitary Gland
G-Protein-Coupled Receptors
Sex Characteristics
Nervous System
Transgenic Mice
Glucocorticoids
Growth Hormone
Hypothalamus
Hyperplasia
Phosphotransferases

ASJC Scopus subject areas

  • Endocrinology

Cite this

Mayo, K. E., Miller, T., DeAlmeida, V., Godfrey, P., Zheng, J., Cunha, S. R., ... Frohman, L. (2000). Regulation of the pituitary somatotroph cell by GHRH and its receptor. Recent Progress in Hormone Research, 55, 237-267.
Mayo, Kelly Edward ; Miller, T. ; DeAlmeida, V. ; Godfrey, P. ; Zheng, Jing ; Cunha, S. R. ; Cutler, G. ; Carter-Su, C. ; Frohman, L. / Regulation of the pituitary somatotroph cell by GHRH and its receptor. In: Recent Progress in Hormone Research. 2000 ; Vol. 55. pp. 237-267.
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Mayo, KE, Miller, T, DeAlmeida, V, Godfrey, P, Zheng, J, Cunha, SR, Cutler, G, Carter-Su, C & Frohman, L 2000, 'Regulation of the pituitary somatotroph cell by GHRH and its receptor', Recent Progress in Hormone Research, vol. 55, pp. 237-267.

Regulation of the pituitary somatotroph cell by GHRH and its receptor. / Mayo, Kelly Edward; Miller, T.; DeAlmeida, V.; Godfrey, P.; Zheng, Jing; Cunha, S. R.; Cutler, G.; Carter-Su, C.; Frohman, L.

In: Recent Progress in Hormone Research, Vol. 55, 01.12.2000, p. 237-267.

Research output: Contribution to journalArticle

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AU - Mayo, Kelly Edward

AU - Miller, T.

AU - DeAlmeida, V.

AU - Godfrey, P.

AU - Zheng, Jing

AU - Cunha, S. R.

AU - Cutler, G.

AU - Carter-Su, C.

AU - Frohman, L.

PY - 2000/12/1

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N2 - Hormones from the hypothalamus mediate interactions between the nervous and endocrine systems by controlling the activity of specific target cells in the anterior pituitary gland. The hypothalamic peptide, growth hormone-releasing hormone (GHRH), acts on pituitary somatotroph cells to stimulate their proliferation during development and to regulate their ability to produce and secrete growth hormone (GH). These actions are mediated by a recently identified receptor for GHRH that belongs to family B-Ill of the G protein-coupled receptor superfamily. The rat GHRH receptor is expressed predominantly in the pituitary gland and in somatotroph cells. To investigate this tissue- and cell-specific expression, the receptor gene has been cloned and characterized. The receptor gene promoter is selectively expressed in pituitary cells and is regulated by the pituitary-specific transcription factor Pit-1. There is a sexual dimorphism in GHRH receptor expression in the rat pituitary, suggesting regulation by gonadal steroids. In addition, glucocorticoids are potent positive regulators of GHRH receptor gene expression. Substantial evidence points to an important role for GHRH in regulating the proliferation and functional activity of the somatotroph cell. This is best observed in the dwarf little mouse, which harbors a mutation in the extracellular domain of the GHRH receptor that abolishes the receptor's hormone-binding and signaling properties, resulting in severe somatotroph hypoplasia. Complementary studies in transgenic mice overexpressing the ligand GHRH reveal corresponding somatotroph hyperplasia. Consistent with these observations, GHRH potently activates the MAP kinase pathway in pituitary somatotroph cells. To better understand the hormone-binding and signaling properties of the GHRH receptor, mutant and chimeric receptors have been analyzed to define domains important for GHRH interaction. The GHRH receptor signals predominantly through cAMP-dependent pathways; however, a variant form of the GHRH receptor with an insertion into the third intracellular domain, generated through alternative RNA processing, binds GHRH but fails to signal, suggesting potential modulation of receptor function at a post-transcriptional level. This chapter will integrate these basic investigations of GHRH and its receptor with current information on the involvement of the GHRH signaling system in human diseases of GH secretion and growth.

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