scholarly journals Soluble forms of the rabbit adipose tissue and liver growth hormone receptors are antigenically identical, but the integral membrane forms differ

1990 ◽  
Vol 267 (2) ◽  
pp. 471-477 ◽  
Author(s):  
R Barnard ◽  
S W Rowlinson ◽  
M J Waters
Keyword(s):  
Growth Hormone ◽  
Adipose Tissue ◽  
Binding Site ◽  
Hormone Receptors ◽  
Membrane Receptors ◽  
Liver Growth ◽  
Tissue Specific ◽  
Membrane Bound ◽  
Gh Receptors ◽  
Binding Subunit

Cytosolic, detergent-solubilized and membrane-bound growth hormone (GH) receptors from rabbit adipose tissue and liver were tested for reactivity with a panel of monoclonal antibodies (MAbs). The cytosolic and detergent-solubilized forms of adipose tissue and liver GH receptors were identically reactive with four precipitating and two hormone-binding-site-directed MAbs. However, the membrane-bound form of the adipose receptor was 1000-fold less reactive with one binding-site-directed MAb (MAb 7) than the membrane-bound liver GH receptor. Reactivity with another inhibitory MAb (MAb 263) was identical for adipose tissue and liver membrane GH receptors. The relative potency of 22,000-Mr and 20,000-Mr forms of human GH was identical in assays with liver and adipose tissue membrane receptors. Thus, contrary to earlier suggestions, the discrepancy between the growth-promoting and insulin-like activities of 20,000-Mr human GH cannot be rationalized by a difference in the affinity of this hormone for ‘somatogenic’ and ‘metabolic’ receptors when the comparison is made in the same species. Cross-linking studies showed that the major GH-binding subunit of liver and adipose tissue GH receptors had the same Mr (54,000 +/- 5000, reduced). The ligand-binding subunits of liver and adipose tissue receptors are identical by several criteria, but one epitope on the adipose tissue receptor appears to be masked upon membrane insertion, possibly by close association with a tissue-specific component. Tissue specificity may be determined by association of a ubiquitous GH-binding subunit with tissue-specific membrane components, rather than by differences in amino acid sequence.

scholarly journals Serum and liver cytosolic growth-hormone-binding proteins are antigenically identical with liver membrane ‘receptor’ types 1 and 2

1986 ◽  
Vol 237 (3) ◽  
pp. 885-892 ◽  
Author(s):  
R Barnard ◽  
M J Waters
Keyword(s):  
Growth Hormone ◽  
Binding Site ◽  
Binding Proteins ◽  
Membrane Receptor ◽  
Rabbit Serum ◽  
Receptor Subtypes ◽  
Hormone Binding ◽  
Liver Growth ◽  
Serum Gh ◽  
Gh Receptors

Studies with a panel of monoclonal antibodies (MAbs) reactive towards the presumptive rabbit liver growth-hormone (GH) receptor show that the rabbit serum GH-binding proteins share seven antigenic determinants (three at the hormone-binding site and four located elsewhere) with the liver cytosolic GH-binding proteins and the putative GH ‘receptors’ associated with the hepatocyte membrane. The rabbit serum binding proteins have an affinity for GH similar to the membrane GH receptors [for human GH, Ka = 2.45 (+/- 0.15) X 10(9) M-1 (mean +/- S.E.M., n = 8)] and high capacity relative to membrane ‘GH receptors’. Analogues of the postulated membrane ‘receptor’ subtypes 1 and 2 exist in the serum, but not subtype 3, which is also absent from liver cytosol. The serum and cytosolic binding proteins have identical cation-dependence properties; hGH binding is Ca2+-dependent, whereas oGH binding is Ca2+-independent. Affinity labelling of hGH-affinity-purified serum binding proteins with 125I-hGH demonstrated a major GH-binding subunit, of Mr 55,000, identical with the major component purified from membranes. In view of their high affinity and capacity, the serum binding proteins could control availability of GH to membrane receptors. It is suggested that the cytosolic binding proteins may be newly synthesized serum binding proteins. The existence of a close relationship between subsets of membrane-associated GH-binding sites, the serum GH-binding proteins and cytosolic GH-binding proteins dictates a reappraisal of earlier ligand-binding studies, which did not distinguish between binding-site subsets in the liver.

Antibodies to Cytoplasmic Sequences of Cloned Liver Growth Hormone (GH) Receptors Recognize GH Receptors Associated with Tyrosine Kinase Activity*

Endocrinology ◽  
1991 ◽  
Vol 129 (3) ◽  
pp. 1659-1670 ◽  
Author(s):  
J. RANDALL STUBBART ◽  
DAVID F. BARTON ◽  
PING-KAUNG K. TAI ◽  
SUSAN E. STRED ◽  
ERELA GORIN ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Tyrosine Kinase ◽  
Kinase Activity ◽  
Tyrosine Kinase Activity ◽  
Liver Growth ◽  
Gh Receptors

Growth hormone receptors in hypothalamic and extra-hypothalamic tissues

1990 ◽  
Vol 5 (3) ◽  
pp. 231-238 ◽  
Author(s):  
R. A. Fraser ◽  
D. Attardo ◽  
S. Harvey
Keyword(s):  
Growth Hormone ◽  
Binding Sites ◽  
Plasma Membranes ◽  
Hormone Receptors ◽  
Cdna Probe ◽  
Rabbit Liver ◽  
Rabbit Brain ◽  
High Affinity ◽  
Age Related ◽  
Gh Receptors

ABSTRACT Central GH receptors (GHR) have been identified in hypothalamic and extra-hypothalamic tissues of rabbit and chicken brains. Plasma membranes of the rabbit brain demonstrated specific saturable high-affinity, low-capacity binding sites for 125I-labelled GH. RNA extracted from hypothalamic and extra-hypothalamic tissues of rabbit and chicken brains contained mRNA that hybridized with a cDNA probe for the rabbit liver GHR. This transcript was of a similar size to the major GHR mRNA moiety in rabbit liver. The expression of these moieties was age related, and higher in adult than in neonatal animals.

Divergent Responses of Serum Insulin-Like Growth Factor-I and Liver Growth Hormone (GH) Receptors to Exogenous GH in Protein-Restricted Rats*

Endocrinology ◽  
1990 ◽  
Vol 126 (2) ◽  
pp. 908-913 ◽  
Author(s):  
J. P. THISSEN ◽  
S. TRIEST ◽  
L. E. UNDERWOOD ◽  
M. MAES ◽  
J. M. KETELSLEGERS
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Serum Insulin ◽  
Insulin Like Growth Factor ◽  
Liver Growth ◽  
Factor I ◽  
Growth Factor I ◽  
Gh Receptors

Demonstration of growth hormone receptors in cultured rat epiphyseal chondrocytes by specific binding of growth hormone and immunohistochemistry

1989 ◽  
Vol 122 (1) ◽  
pp. 69-NP ◽  
Author(s):  
A. Nilsson ◽  
A. Lindahl ◽  
S. Edén ◽  
O. G. P. Isaksson
Keyword(s):  
Growth Hormone ◽  
Hormone Receptors ◽  
Cultured Cells ◽  
Specific Binding ◽  
Calf Serum ◽  
Male Rats ◽  
Scatchard Analysis ◽  
Cells Cultured ◽  
Gh Receptors ◽  
In Cells

ABSTRACT Growth hormone has been reported to exert direct effects on rat and rabbit epiphyseal chondrocytes in vitro, indicating that GH interacts with specific receptors on these cells. To investigate this possibility, binding of GH to cultured rat epiphyseal chondrocytes was studied under various experimental conditions. Chondrocytes were isolated enzymatically from epiphyseal growth plates of the proximal tibia of 20-day-old male rats and were cultured in monolayer in Ham's F-12 medium supplemented with 10% calf serum and 1% of a serum substitute. The cells were seeded at various densities (25 000–200 000 cells/well) and cultured for 5–16 days. Twenty-four hours before binding experiments, the medium containing calf serum was changed for one containing serum obtained from hypophysectomized rats, in order to avoid binding of GH present in the calf serum. Binding was studied by incubating 125I-labelled human GH (hGH) with the cells in the presence or absence of various concentrations of unlabelled hGH, bovine GH (bGH), rat GH (rGH) and ovine prolactin (oPRL). Specific binding could be demonstrated in cells cultured for 5–16 days. Binding was dependent upon time and temperature, and maximal binding was obtained by incubating the labelled hormone for 4–6 h at 24 °C. An increase in binding was noted between 7 and 12 days in culture. In cells cultured for 12 days, addition of unlabelled hGH, bGH or rGH caused a dose-dependent displacement of 125I-labelled hGH, whereas oPRL was ineffective. Scatchard analysis resulted in a linear plot, and the number of binding sites/cell was approximately 5700, with a dissociation constant of 0·46 nmol/l. The increase in binding between days 7 and 12 was independent of the density of seeded cells, but total binding was higher if the cells were seeded at a low density. By using a monoclonal antibody to the rabbit GH receptor, specific staining could be demonstrated immunohistochemically in the cultured cells. The results show the presence of GH receptors in cultured rat epiphyseal chondrocytes and also show that the culture conditions influence the expression of GH receptors. Journal of Endocrinology (1989) 122, 69–77

scholarly journals Growth hormone acts on liver to stimulate autophagy, support glucose production, and preserve blood glucose in chronically starved mice

2019 ◽  
Vol 116 (15) ◽  
pp. 7449-7454 ◽  
Author(s):  
Fei Fang ◽  
Xuanming Shi ◽  
Michael S. Brown ◽  
Joseph L. Goldstein ◽  
Guosheng Liang
Keyword(s):  
Electron Microscopy ◽  
Growth Hormone ◽  
Adipose Tissue ◽  
Blood Glucose ◽  
Calorie Restriction ◽  
Glucose Production ◽  
Plasma Growth Hormone ◽  
Energy Stores ◽  
Preserve Blood ◽  
Gh Receptors

When mice are subjected to 60% calorie restriction for several days, they lose nearly all of their body fat. Although the animals lack energy stores, their livers produce enough glucose to maintain blood glucose at viable levels even after a 23-hour fast. This adaptation is mediated by a marked increase in plasma growth hormone (GH), which is elicited by an increase in plasma ghrelin, a GH secretagogue. In the absence of ghrelin, calorie-restricted mice develop hypoglycemia, owing to diminished glucose production. To determine the site of GH action, in the current study we used CRISPR/Cas9 and Cre recombinase technology to produce mice that lack GH receptors selectively in liver (L-Ghr−/− mice) or in adipose tissue (Fat-Ghr−/− mice). When subjected to calorie restriction and then fasted for 23 hours, the L-Ghr−/− mice, but not the Fat-Ghr−/− mice, developed hypoglycemia. The fall in blood glucose in L-Ghr−/− mice was correlated with a profound drop in hepatic triglycerides. Hypoglycemia was prevented by injection of lactate or octanoate, two sources of energy to support gluconeogenesis. Electron microscopy revealed extensive autophagy in livers of calorie-restricted control mice but not in L-Ghr−/− mice. We conclude that GH acts through its receptor in the liver to activate autophagy, preserve triglycerides, enhance gluconeogenesis, and prevent hypoglycemia in calorie-restricted mice, a model of famine.

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