Transgenic mice expressing the human growth hormone gene provide a model system to study human growth hormone synthesis and secretion in non-tumor-derived pituitary cells: differential effects of dexamethasone and thyroid hormone

Mol Cell Endocrinol. 2011 Oct 15;345(1-2):48-57. doi: 10.1016/j.mce.2011.07.010. Epub 2011 Jul 12.

Abstract

Growth hormone (GH) is regulated by pituitary and hypothalamic factors as well as peripheral endocrine factors including glucocorticoids and thyroid hormone. Studies on human GH are limited largely to the assessment of plasma levels in endocrine disorders. Thus, insight into the regulation of synthesis versus secretion has come mainly from studies done on non-human GH and/or pituitary tumor cells. However, primate and non-primate GH gene loci have differences in their structure and, by extension, regulation. We generated transgenic (171hGH/CS-TG) mice containing the intact hGH1 gene and locus control region, including sequences required for integration-independent and preferential pituitary expression. Here, we show hGH co-localizes with mouse (m) GH in somatotrophs in situ and in primary pituitary cells. Dexamethasone treatment increased hGH and mGH, as well as GH releasing hormone (GHRH) receptor RNA levels, and hGH release was stimulated by GHRH treatment. By contrast, triiodothyronine decreased or had no effect on hGH and mGH production, respectively, and the negative effect on hGH was also seen in the presence of dexamethasone. Thus, 171hGH/CS-TG mouse pituitary cultures represent a model system to investigate hormonal control of hGH synthesis and secretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Dexamethasone / pharmacology*
  • Female
  • Ghrelin / pharmacology
  • Growth Hormone-Releasing Hormone / pharmacology
  • Human Growth Hormone / genetics*
  • Human Growth Hormone / metabolism*
  • Humans
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Transgenic
  • Models, Biological*
  • Pituitary Gland / cytology*
  • Pituitary Gland / drug effects
  • Pituitary Gland / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Ghrelin / genetics
  • Receptors, Ghrelin / metabolism
  • Receptors, Neuropeptide / genetics
  • Receptors, Neuropeptide / metabolism
  • Receptors, Pituitary Hormone-Regulating Hormone / genetics
  • Receptors, Pituitary Hormone-Regulating Hormone / metabolism
  • Thyroid Hormones / pharmacology*
  • Triiodothyronine / pharmacology

Substances

  • Ghrelin
  • RNA, Messenger
  • Receptors, Ghrelin
  • Receptors, Neuropeptide
  • Receptors, Pituitary Hormone-Regulating Hormone
  • Thyroid Hormones
  • Triiodothyronine
  • Human Growth Hormone
  • Dexamethasone
  • Growth Hormone-Releasing Hormone
  • somatotropin releasing hormone receptor