Localization of the growth hormone receptor/binding protein in skin

ABSTRACT Acromegaly is characterized by coarsening of facial features, acanthosis nigricans, hypertrichosis and oily skin. To determine the site through which GH exerts these effects, we have used immunohistochemistry to localize the GH receptor/binding protein (BP) in rat, rabbit and human skin. Three monoclonal antibodies (MAb 1, 43, 263) were immunoreactive in identical locations, whereas no immunoreactivity was evident when control monoclonal antibodies (MAb 50.8 and MAb 7 (rat)) were used. Skin from neonatal and adult animals was used to determine whether GH receptor/BP expression was developmentally regulated. Immunoreactivity of the GH receptor/BP in the three species was consistently localized in the stratum basale and stratum spinosum. Intermittent staining was observed in the stratum granulosum. Scattered basal epidermal cells often displayed more intense immunoreactivity. This distribution was observed at all maturational stages examined. Intense GH receptor/BP immunoreactivity was observed in all histological layers of the lower one-third of hair follicles and in hair matrix cells of the dermal papillae. Immunoreactivity was also detected in the outer epithelial root sheath of the upper two-thirds of hair follicles, in sebaceous glands and in fibroblasts of the connective tissue sheath surrounding the follicle. GH receptor/BP immunoreactivity was also present in the secretory duct and myoepithelial cells of human eccrine sweat glands. Fibroblasts, Schwann cells of peripheral nerve fascicles, skeletal muscle cells and adipocytes of the dermis were also immunoreactive as were medial smooth muscle and endothelial cells of arteries. These results provide evidence that GH acts locally on the epidermis and epidermal appendages concordant with our recent localization of GH receptor/BP to epithelial cell types of the gastrointestinal and reproductive systems. Journal of Endocrinology (1990) 126, 467–472

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The nuclear growth hormone receptor binding protein. Antigenic and physicochemical characterization.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)54619-6 ◽

1991 ◽

Vol 266 (33) ◽

pp. 22645-22652

Author(s):

P.E. Lobie ◽

R. Barnard ◽

M.J. Waters

Keyword(s):

Growth Hormone ◽

Receptor Binding ◽

Hormone Receptor ◽

Growth Hormone Receptor ◽

Binding Protein ◽

Physicochemical Characterization ◽

Receptor Binding Protein

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Protection against Diabetes-Induced Nephropathy in Growth Hormone Receptor/Binding Protein Gene-Disrupted Mice1

Endocrinology ◽

10.1210/endo.141.1.7284 ◽

2000 ◽

Vol 141 (1) ◽

pp. 163-168 ◽

Cited By ~ 32

Author(s):

Linda L. Bellush ◽

Sophie Doublier ◽

Amy N. Holland ◽

Liliane J. Striker ◽

Gary E. Striker ◽

...

Keyword(s):

Growth Hormone ◽

Receptor Binding ◽

Hormone Receptor ◽

Growth Hormone Receptor ◽

Protein Gene ◽

Binding Protein ◽

Binding Protein Gene ◽

Receptor Binding Protein

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Prenatal expression of the growth hormone (GH) receptor/binding protein in the rat: a role for GH in embryonic and fetal development?

Development ◽

10.1242/dev.114.4.869 ◽

1992 ◽

Vol 114 (4) ◽

pp. 869-876

Author(s):

J. Garcia-Aragon ◽

P.E. Lobie ◽

G.E. Muscat ◽

K.S. Gobius ◽

G. Norstedt ◽

...

Keyword(s):

Growth Hormone ◽

Polymerase Chain Reaction ◽

Receptor Binding ◽

Fetal Growth ◽

Binding Protein ◽

Chain Reaction ◽

Rat Fetus ◽

Gh Receptor ◽

Polymerase Chain ◽

Receptor Binding Protein

Although fetal growth is generally considered to be independent of pituitary growth hormone (GH), it is possible that pituitary GH plays a modulatory role in organ development or that a GH-like substance of non pituitary origin may influence fetal growth through the GH receptor. Accordingly, we have used immunohistochemistry, northern blot analysis, the reverse transcriptase-polymerase chain reaction and solution hybridization to study the ontogeny of the GH receptor/binding protein (BP) from the 12-day-old embryo (E12) to the E18 rat fetus. GH receptor/BP immunoreactivity was observed in all major organ systems of the E18 rat fetus and was not preferentially associated with any germ layer derivative. A general increase in GH receptor/BP immunoreactivity was evident from E12 to E18, with a marked increase occurring between E16 and E18. Hemangioblastic tissue was, however, strongly or intensely immunoreactive at all stages of development, as was the placenta. Most noteworthy of the other tissues expressing GH receptor/BP immunoreactivity by day 18 were skeletal and smooth muscle, chondroprogenitor cells, epithelial lining cells, neuronal ganglia, ependymal cells and the adrenal cortex. In the placenta, the most prominent immunoreactivity was associated with decidual cells. Total RNA was isolated from E12 to E18 rat fetuses and adult rat liver. Northern hybridization with a 35S-labelled rat GH receptor cRNA probe revealed that 3.9 kb and 1.2 kb transcripts complementary to the rat GH receptor riboprobe are present from at least E16. The existence of GH receptor mRNA at E12 and E14 was demonstrated by the polymerase chain reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

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Functional cooperativity mediated by rationally selected combinations of human monoclonal antibodies targeting the henipavirus receptor binding protein

10.1101/2021.02.17.431743 ◽

2021 ◽

Author(s):

Michael P. Doyle ◽

Nurgun Kose ◽

Viktoriya Borisevich ◽

Elad Binshtein ◽

Moushimi Amaya ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Receptor Binding ◽

Binding Protein ◽

Severe Disease ◽

Hendra Virus ◽

Human Monoclonal Antibodies ◽

Human Mabs ◽

Viral Attachment ◽

Antigenic Sites ◽

Receptor Binding Protein

AbstractHendra virus (HeV) and Nipah virus (NiV), the prototypic members of the Henipavirus (HNV) genus, are emerging, zoonotic paramyxoviruses known to cause severe disease across six mammalian orders, including humans (Eaton et al., 2006). While several research groups have made strides in developing candidate vaccines and therapeutics against henipaviruses, such countermeasures have not been licensed for human use, and significant gaps in knowledge about the human immune response to these viruses exist. To address these gaps, we isolated a large panel of human monoclonal antibodies (mAbs) from the B cells of an individual with prior occupation-related exposure to the equine HeV vaccine (Equivac® HeV). Competition-binding and hydrogen-deuterium exchange mass spectrometry (HDX-MS) studies identified at least six distinct antigenic sites on the HeV/NiV receptor binding protein (RBP) that are recognized by human mAbs. Antibodies recognizing multiple antigenic sites potently neutralized NiV and/or HeV isolates in vitro. The most potent class of cross-reactive antibodies achieved neutralization by blocking viral attachment to the host cell receptors ephrin-B2 and ephrin-B3. Antibodies from this class mimic receptor binding by inducing a receptor-bound conformation to the HeV-RBP protein tetramer, exposing an epitope that appears to lie hidden in the interface between protomers within the HeV-RBP tetramer. Antibodies that recognize this cryptic epitope potently neutralized HeV and NiV. Flow cytometric studies using cell-surface-displayed HeV-RBP protein showed that cross-reactive, neutralizing mAbs from each of these classes cooperate for binding. In a highly stringent hamster model of NiVB infection, antibodies from both classes reduced morbidity and mortality and achieved synergistic protection in combination and provided therapeutic benefit when combined into two bispecific platforms. These studies identified multiple candidate mAbs that might be suitable for use in a cocktail therapeutic approach to achieve synergistic antiviral potency and reduce the risk of virus escape during treatment.

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