HISTONES AS EXTRACELLULAR MESSENGERS: EFFECTS ON GROWTH HORMONE SECRETION

Histones display hormone-like properties when present in extracellular fluids. The authors report that histones H2A and H2B possess growth hormone (GH)-releasing activity in vitroand describe the specificity and signal transduction pathways involved in these effects. Perfused and incubated rat pitui...

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Bibliographic Details
Published in:Cell biology international 1997-12, Vol.21 (12), p.787-792
Main Authors: BROWN, O.A., SOSA, Y.E., GOYA, R.G.
Format: Article
Language:English
Subjects:
Animals
calcium
diacylglycerol
Drug Interactions
Extracellular Space - drug effects
Extracellular Space - physiology
Female
Gonadotropin-Releasing Hormone - administration & dosage
Growth Hormone - secretion
histones
Histones - administration & dosage
Histones - pharmacology
Histones - physiology
In Vitro Techniques
Kinetics
MB35
Oligopeptides - administration & dosage
Perfusion
pituitary cells
Pituitary Gland, Anterior - cytology
Pituitary Gland, Anterior - drug effects
Pituitary Gland, Anterior - secretion
Rats
Rats, Sprague-Dawley
Signal Transduction - drug effects
Signal Transduction - physiology
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Summary:Histones display hormone-like properties when present in extracellular fluids. The authors report that histones H2A and H2B possess growth hormone (GH)-releasing activity in vitroand describe the specificity and signal transduction pathways involved in these effects. Perfused and incubated rat pituitary cells were used in different sets of experiments and GH release was measured by radio-immunoassay (RIA). Perfusion of cells with 30 μ mhistone H2A or H2B, generated significant GH secretory responses. Cells incubated with histone H2A showed a dose- and time-dependent stimulatory effect on GH release which was blocked by peptide MB35, a synthetic fragment of histone H2A. Incubation of pituitary cells with the GH secretagogue GHRP-6, and histones revealed an additive release of GH, whereas GHRH and histones revealed a synergistic effect. The basic peptide poly-Lys did not mimetize the action of histones. Both EGTA and the protein kinase C inhibitor trifluoperazine, but not the calcium ionophre A23187, were able to reduce significantly the GH response of somatotrophs to histones. Pituitary cell incubation with 30 μ mforskolin alone or in the presence of H2A or H2B, stimulated GH release in the same magnitude. The results confirm previous evidence that histones may act as hypophysotropic signals and suggest, although do not prove, that this activity is receptor dependent. Calcium- and diacylglycerol-associated pathways participate in these effects.
ISSN:1065-6995
1095-8355
DOI:10.1006/cbir.1998.0203