Hypothalamic GH receptor gene expression in the rat: effects of altered GH status

1995 ◽  
Vol 147 (2) ◽  
pp. 225-234 ◽  
Author(s):  
P A Bennett ◽  
A Levy ◽  
S Sophokleous ◽  
I C A F Robinson ◽  
S L Lightman
Keyword(s):  
Gene Expression ◽  
Receptor Gene ◽  
Feedback Regulation ◽  
Receptor Expression ◽  
Physiological Regulation ◽  
Background Strain ◽  
Gh Receptor ◽  
The Central Nervous System ◽  
Receptor Gene Expression

Abstract GH synthesis and release from the anterior pituitary is governed by the opposing actions of somatostatin (SS) and GH-releasing factor (GRF), derived from the periventricular and arcuate nucleus (ARC) of the hypothalamus respectively. GH is known to regulate its own release by hypothalamic autofeedback mechanisms, but the extent to which this is a direct effect rather than indirectly via the generation of IGFs is still a subject of debate. GH receptors are known to be present in the hypothalamus, but their physiological regulation is poorly understood. We therefore used in situ hybridization histochemistry to investigate the effects of GH status on hypothalamic GH receptor gene expression, using hypophysectomized normal and dw/dw dwarf rats as models of acquired and congenital GH deficiency. Hypophysectomy resulted in a timedependent reduction in GH receptor gene expression. ARC GH receptor transcripts in untreated dw/dw dwarf rats were half those found in normal animals of the same background strain (16·8±1·7 vs 9·3± 1·9 d.p.m./mg, P<0·05). Increasing circulating GH by peripheral infusion of 200 μg human GH (hGH)/day for 6 days increased ARC GH receptor expression in dw/dw rats to normal. In contrast, central infusions of hGH at 26·4 and 79·2 μg/day for 6 days in normal rats lowered ARC GH receptor gene expression. The sensitivity of GH receptor gene expression within the central nervous system to peripheral and central GH levels suggests that feedback regulation of GRF and/or SS may be mediated directly by these receptors, and that the sensitivity to GH feedback is also subject to autoregulation by GH altering its own receptor expression. Journal of Endocrinology (1995) 147, 225–234

scholarly journals Inhibition of Growth Hormone Receptor Gene Expression by Saturated Fatty Acids: Role of Krüppel-Like Zinc Finger Factor, ZBP-89

2006 ◽  
Vol 20 (11) ◽  
pp. 2747-2760 ◽  
Author(s):  
Jamuna Thimmarayappa ◽  
Jinhong Sun ◽  
Laura E. Schultz ◽  
Prapai Dejkhamron ◽  
Chunxia Lu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Diabetes Mellitus ◽  
Palmitic Acid ◽  
Receptor Gene ◽  
Inhibitory Effect ◽  
Cis Elements ◽  
Gh Receptor ◽  
Steady State Levels ◽  
Receptor Gene Expression

Abstract The expression and function of the GH receptor is critical for the actions of pituitary GH in the intact animal. The role of systemic factors in the reduced expression of the GH receptor and consequent GH insensitivity in pathological states such as sepsis, malnutrition, and poorly controlled diabetes mellitus is unclear. In the current study, we demonstrate that saturated (palmitic and myristic; 50 μm) fatty acids (FA) inhibit activity of the promoter of the major (L2) transcript of the GH receptor gene; unsaturated (oleic and linoleic) FA (200 μm) do not alter activity of the promoter. Comparable effects with palmitic acid and the nonmetabolizable analog bromo-palmitic acid, and failure of triacsin C to abrogate palmitic acids effects on GH receptor expression indicate that this effect is due to direct action(s) of FA. Palmitic acid, but not the unsaturated FA linoleic acid, decreased steady-state levels of endogenous L2 mRNA and GHR protein in 3T3-L1 preadipocytes. The effect of FA was localized to two cis elements located approximately 600 bp apart on the L2 promoter. EMSA and chromatin immunoprecipitation assays established that both these cis elements bind the Krüppel-type zinc finger transcription factor, ZBP-89. Ectopic expression of ZBP-89 amplified the inhibitory effect of FA on L2 promoter activity and on steady-state levels of endogenous L2 mRNA in 3T3-L1 preadipocytes. Mutational analyses of the two ZBP-89 binding sites revealed that both the sites are essential for palmitic acid’s inhibitory effect on the L2 promoter and for the enhancing effect of ZBP-89 on palmitic acid-induced inhibition of the L2 promoter. Our results establish a molecular basis for FA-induced inhibition of GH receptor gene expression in the pathogenesis of acquired GH insensitivity in pathological states such as poorly controlled diabetes mellitus and small for gestational age.

scholarly journals Modulation of glomerular endothelin and endothelin receptor gene expression in aminonucleoside-induced nephrosis.

1995 ◽  
Vol 5 (8) ◽  
pp. 1585-1590
Author(s):  
T Nakamura ◽  
I Ebihara ◽  
M Fukui ◽  
S Osada ◽  
Y Tomino ◽  
...  
Keyword(s):  
Gene Expression ◽  
Receptor Gene ◽  
Mrna Level ◽  
Experimental Period ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Puromycin Aminonucleoside ◽  
Receptor Mrna ◽  
Etb Receptor ◽  
Receptor Gene Expression

This study assessed glomerular endothelin (ET)-1, ET-3, and ET-receptor A and B mRNA levels in puromycin aminonucleoside (PAN)-induced nephrosis. During the nephrotic stage, 8 days after PAN injection, ET-1 and ETB receptor mRNA were elevated by 2.8 +/- 0.8-fold (P < 0.01) and 2.4 +/- 0.9-fold (P < 0.01), respectively, as compared with controls. These mRNA levels decreased to control levels by Day 20, when the nephrosis was in remission. In contrast, glomerular ETA receptor mRNA levels did not change in PAN nephrosis or control rats during the experimental period. ET-3 mRNA was not detected in the glomeruli of PAN nephrosis or control rats. Additionally, plasma ET concentration and glomerular ET production were measured in PAN nephrosis and control rats by radio-immunoassay. Eight days after PAN injection, ET-1 levels in plasma and glomeruli were not significantly altered in rats with PAN-induced nephrosis (glomeruli, 104.68 +/- 16.46 pg/mg of protein versus 98.24 +/- 13.68 pg/mg of protein; plasma, 2.68 +/- 1.10 versus 2.52 +/- 0.98 pg/mL). The administration of methylprednisolone to PAN rats resulted in the rapid disappearance of proteinuria and partially attenuated the increased ET-1 and ETB receptor gene expression in the glomeruli. These data indicate that glomerular ET-1 and ETB receptor expression in PAN nephrosis in increased at the mRNA level and that methylprednisolone treatment results in an attenuated increase.

Visualization of gene expression of short and long forms of prolactin receptor in rat digestive tissues

1994 ◽  
Vol 266 (5) ◽  
pp. G807-G815 ◽  
Author(s):  
A. Ouhtit ◽  
P. A. Kelly ◽  
G. Morel
Keyword(s):  
Gene Expression ◽  
Gastrointestinal Tract ◽  
Short Form ◽  
Receptor Gene ◽  
Prolactin Receptor ◽  
High Signal ◽  
Long Form ◽  
Receptor Gene Expression ◽  
Receptor Mrnas

Several effects of prolactin have been characterized in various tissues of the gastrointestinal tract. In the present study, the expression of short and long forms of prolactin receptor was explored and quantified in the digestive tract and correlated to the prolactin specific functions. Sections of all digestive tissues were analyzed by in situ hybridization, using 35S-labeled oligoprobes unique to each form of receptor. Macroautoradiogram signals were quantified and expressed in arbitrary units. In rat liver, prolactin receptor mRNAs are expressed to a much greater degree in females than in males. The short-form transcript is significantly expressed to a greater degree in liver, whereas the long form predominates in the pancreas and esophagus. In the remainder of the gastrointestinal tract, there is an equivalent distribution of short- and long-form transcripts. Relatively high signal intensities are seen in the stomach, duodenum, jejunum, ileum, and colon, whereas the rectum is essentially negative. The identification of prolactin receptor gene expression to limited regions should help establish specific functions associated with this hormone in the digestive tissues.

Parathyroid hormone receptor stimulation induces human adipocyte lipolysis and browning

2021 ◽  
Vol 184 (5) ◽  
pp. 687-697
Author(s):  
Peter Breining ◽  
Steen B Pedersen ◽  
Mads Kjolby ◽  
Jacob B Hansen ◽  
Niels Jessen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Parathyroid Hormone ◽  
Receptor Gene ◽  
Receptor Expression ◽  
Whole Body ◽  
Brown Adipocyte ◽  
Cell Models ◽  
Receptor Stimulation ◽  
Receptor Gene Expression

Objective Activation of brown adipose tissue is a promising strategy to treat and prevent obesity and obesity-related disorders. Activation of uncoupling protein 1 (UCP1) leads to uncoupled respiration and dissipation of stored energy as heat. Induction of UCP1-rich adipocytes in white adipose tissue, a process known as ‘browning’, serves as an alternative strategy to increase whole body uncoupling capacity. Here, we aim to assess the association between parathyroid hormone (PTH) receptor expression and UCP1 expression in human adipose tissues and to study PTH effects on human white and brown adipocyte lipolysis and UCP1 expression. Design A descriptive study of human neck adipose tissue biopsies substantiated by an interventional study on human neck-derived adipose tissue cell models. Methods Thermogenic markers and PTH receptor gene expression are assessed in human neck adipose tissue biopsies and are related to individual health records. PTH-initiated lipolysis and thermogenic gene induction are assessed in cultured human white and brown adipocyte cell models. PTH receptor involvement is investigated by PTH receptor silencing. Results PTH receptor gene expression correlates with UCP1 gene expression in the deep-neck adipose tissue in humans. In cell models, PTH receptor stimulation increases lipolysis and stimulates gene transcription of multiple thermogenic markers. Silencing of the PTH receptor attenuates the effects of PTH indicating a direct PTH effect via this receptor. Conclusion PTH 1 receptor stimulation by PTH may play a role in human adipose tissue metabolism by affecting lipolysis and thermogenic capacity.

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