Cloning and characterization of the cDNAs for human and rat corticotropin releasing factor-binding proteins

@article{Potter1991CloningAC,
  title={Cloning and characterization of the cDNAs for human and rat corticotropin releasing factor-binding proteins},
  author={Ellen Potter and Dominic P. Behan and Wolfgang H. Fischer and Elizabeth A. Linton and Philip J. Lowry and Wylie W. Vale},
  journal={Nature},
  year={1991},
  volume={349},
  pages={423-426}
}
CORTICOTROPIN-releasing factor (CRF)1, is a potent stimulator of synthesis and secretion of preopiomelanocortin-derived peptides. Although CRF concentrations in the human peripheral circulation are normally low2–4, they increase throughout pregnancy4–8 and fall rapidly after parturition. Maternal plasma CRF probably originates from the placenta, which responds to the bioactive peptide5,9,10 and produces the peptide9and its messenger RNA11. Even though CRF concentrations in late gestational… 

Corticotropin-releasing factor and its binding protein in human plasma.

  • P. Lowry
  • Biology, Medicine
    Ciba Foundation symposium
  • 1993
With the cloning of the cDNA for CRF-BP, sufficient pure material has become available for the development of a radioimmunoassay and when mixed with appropriate amounts of CRF completely inhibits the ACTH-releasing activity of the peptide in vitro.

Modulatory Actions of Corticotropin‐releasing Factor–binding Protein a

The purified protein maintained all the characteristics of the crude human plasma protein, in that it bound CRF with high affinity, had a low affinity for the ovine peptide, and gave a dose-dependent inhibition of CRF-induced ACTH secretion in vitro.

Heterogeneity of the human corticotropin-releasing factor-binding protein.

Evidence is presented for a C-terminally truncated form of the native binding protein in the plasma of subjects suffering from rheumatoid arthritis, which may parallel the in vitro truncation.

Expression cloning of a human corticotropin-releasing-factor receptor.

The cloning of a cDNA coding for a CRF receptor from a human corticotropic tumor library is reported, which encodes a 415-amino acid protein comprising seven putative membrane-spanning domains and is structurally related to the calcitonin/vasoactive intestinal peptide/growth hormone-releasing hormone subfamily of G protein-coupled receptors.

Corticotropin releasing factor and its binding protein

Corticotropin-Releasing Factor-Bind Concentrations in Plasma of Patients Pituitary-Adrenal Disorders ink

The findings suggest that the immunoreactive CRF-BP concentration in human plasma was decreased by glucocorticoids, at least under chronic conditions.

7 CORTICOTROPIN-RELEASING FACTOR : PHYSIOLOGY , PHARMACOLOGY , AND ROLE IN CENTRAL NERVOUS SYSTEM DISORDERS

This chapter provides an overview of the CRF system and its related receptor targets and identifies a second receptor subtype (termed CRF2), which has now been localized and characterized in a variety of species.
...

References

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Evidence for local stimulation of ACTH secretion by corticotropin-releasing factor in human placenta

Using a monolayer primary culture of human placental cells, it is found that CRF stimulates secretion of peptides containing the ACTH sequence in the placenta in a dose-dependent manner, as it does in the pituitary.

Immunoreactive corticotropin-releasing factor in human plasma.

It is found that most plasma I-CRF levels were affected by stress, negative feedback, and circadian rhythm, and that other extrahypothalamic tissues cannot be ruled out as a minor source of plasma I.CRF.

The corticotropin releasing hormone gene is expressed in human placenta.

Isolation of the human plasma corticotrophin-releasing factor-binding protein.

A 10(7)-fold purification of the hCRF-BP resulted in a preparation estimated to be 95% pure, with an overall yield of 5%, which matched the original molecular weight estimate based on the elution position of the binding protein on Sephacryl S-200.

A SPECIFIC CARRIER SUBSTANCE FOR HUMAN CORTICOTROPHIN RELEASING FACTOR IN LATE GESTATIONAL MATERNAL PLASMA WHICH COULD MASK THE ACTH‐RELEASING ACTIVITY

Using gel chromatography and CRF‐41 immunoradiometric assay, it is shown that binding of the peptide to its plasma carrier can be disrupted by treatment with urea, and the more concentrated chromatographic fractions at the apex of the carrier‐bound CRf‐41 peak showed reduced bioactivity, indicating that the higher concentrations of carrier in the original maternal plasma could mask the ACTH‐releasing activity of CRF•41.

Corticotropin-releasing factor-like activity in human placental extracts.

In cultures of rat anterior pituitary cells, the placental CRF-like material shows bioactivity similar to that of the partially purified rat hypothalamic CRF and synthetic ovine C R F on the release of adrenocorticotropin and (β-endorphin).

High levels of corticotropin-releasing hormone immunoactivity in maternal and fetal plasma during pregnancy.

It is concluded that a large amount of CRHi is secreted by the placenta into both the maternal and fetal circulation during pregnancy and suggest that this may be an important modulator of the mothers and fetal hypothalamic-pituitary-adrenal axis during gestation.

Measurement of circulating corticotrophin-releasing factor in man.

In normal subjects no changes in plasma CRF-41 occurred after insulin-induced hypoglycaemia, treatment with dexamethasone or feeding, and changes in the concentrations did not reflect circadianChanges in plasma concentrations of cortisol.

Corticotropin-releasing hormone (CRH)-binding protein: reduction in the adrenocorticotropin-releasing activity of placental but not hypothalamic CRH.

It is proposed that stress-induced CRH release will not be similarly quenched by the CRH-BP in the hypothalamic portal system, as the concentration of CRH released will be high, and the exposure time before reaching pituitary corticotropes will be low.