The Human Growth Hormone-Releasing Hormone Transgenic Mouse as a Model of Modest Obesity: Differential Changes in Leptin Receptor (OBR) Gene Expression in the Anterior Pituitary and Hypothalamus after Fasting and OBR Localization in Somatotrophs*
| Autor: | Aihua Cai, James F. Hyde |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Male
Pituitary gland medicine.medical_specialty Transcription Genetic Somatotropic cell Hypothalamus Adipose tissue Mice Transgenic Receptors Cell Surface Biology Growth Hormone-Releasing Hormone Mice Endocrinology Anterior pituitary Pituitary Gland Anterior Reference Values Internal medicine medicine Animals Humans Obesity RNA Messenger Leptin receptor Leptin Fasting Growth hormone–releasing hormone medicine.anatomical_structure Adipose Tissue Gene Expression Regulation Organ Specificity Receptors Leptin Carrier Proteins |
| Zdroj: | Endocrinology. 140:3609-3614 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/endo.140.8.6925 |
| Popis: | We reported previously an increase in leptin receptor (OBR) gene expression in the anterior pituitary of human GH-releasing hormone (hGHRH) transgenic mice. The primary goal of this study was to investigate the possible mechanisms regulating OBR expression in these mice. Compared with normal sibling controls, hGHRH transgenic mice had significantly greater amounts of abdominal fat, higher levels of leptin messenger RNA (mRNA), and a 2-fold increase in plasma leptin concentrations. Despite normal plasma glucose levels, hGHRH transgenic mice had 4.5-fold elevated levels of plasma insulin. Using a ribonuclease protection assay, we measured the mRNA levels of the OBR long form (OBR(L)) in the anterior pituitary and hypothalamus after 48 h of fasting. In the anterior pituitary, food deprivation induced dramatic increases in OBR(L) mRNA levels in both normal and transgenic mice. In contrast, in the hypothalamus, fasting resulted in a significant decrease in OBR(L) gene expression in normal mice, and no changes were detected in hGHRH transgenic mice. Using dual in situ hybridization, OBR(L) mRNA was detected in somatotrophs. Moreover, the number of OBR(L)-positive pituitary cells as well as the percentage of OBR(L)-positive cells that express GH mRNA were increased in transgenic mice. In conclusion, 1) the modest obesity in hGHRH transgenic mice is associated with increases in leptin synthesis and secretion as well as insulin secretion; 2) GH and/or GHRH as well as leptin and insulin may differentially contribute to the changes in OBR(L) gene expression in the anterior pituitary and the hypothalamus; 3) the response of OBR(L) gene expression in the hypothalamus to fasting is absent in the modestly obese hGHRH transgenic mice; and 4) somatotrophs are target cells for leptin, and the increase in OBR(L) gene expression in the pituitary of hGHRH transgenic mice is due at least in part to the increase in the number of cells expressing OBR(L). |
| Databáze: | OpenAIRE |
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