Ligand requirements of the human corticotropin-releasing factor-binding protein.

Sutton, Steve W.; Behan, Dominic P.; Lahrichi, S.; Kaiser, R.; Corrigan, A; Lowry, P. J.; Potter, Ellen; Perrin, Marilyn H.; Rivier, Jean; Vale, Wylie

doi:10.1210/endo.136.3.7867564

Cited by 104 publications

(34 citation statements)

References 25 publications

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“…To test this hypothesis hCRH and ovine CRH should be used in parallel as pharmacological stimuli in future studies. Sutton et al [36]have shown that CRH-BP binds hCRH with high affinity but ovine CRH with low affinity. Therefore, a comparison of endocrine responses to ovine CRH in contrast to hCRH could elucidate the role of CRH-BP in young and elderly humans.…”

Section: Discussionmentioning

confidence: 99%

Psychological and Endocrine Responses to Psychosocial Stress and Dexamethasone/ Corticotropin-Releasing Hormone in Healthy Postmenopausal Women and Young Controls: The Impact of Age and a Two-Week Estradiol Treatment

Kudielka¹,

Schmidt-Reinwald²,

Hellhammer³

et al. 1999

Neuroendocrinology

124

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In this placebo-controlled double-blind study, psychological and endocrine stress responses were investigated in healthy postmenopausal placebo-treated women (n = 15; 60–75 years; placebo via transdermal patches), healthy postmenopausal estradiol-treated women (n = 13; 60–79 years; 0.1 mg 17β-estradiol daily via transdermal patches) and young controls (n = 15; 20–31 years; untreated). The aged subjects received estradiol or placebo treatment for 14 days. All subjects were then exposed to the ‘Trier Social Stress Test’ (TSST) and the dexamethasone (Dex)-human corticotropin-releasing hormone (hCRH) test (100 µg hCRH after premedication with 1.5 mg Dex). Psychological parameters including perceived stressfulness, mood and subjective well-being were measured by visual analog scales, a mood questionnaire and a mood diary, respectively. Results show that the TSST induced significant increases in adrenocorticotropin (ACTH), free salivary cortisol, total plasma cortisol and heart rates (all p < 0.0001). Regardless of age, comparable hormonal response patterns were observed in the TSST as indicated by similar peak levels and recovery phases. Visual analog scales confirmed that the same amount of stress was experienced by young and elderly subjects. In both age groups, hCRH injection after Dex premedication provoked significant increases in ACTH, free salivary cortisol and total plasma cortisol (all p < 0.0001). In contrast to the psychosocial stressor, elderly women were found to respond with a markedly enhanced cortisol response compared to young controls in the Dex-CRH test (p < 0.025). Additional investigation of morning cortisol profiles could not reveal any age-related differences in basal hypothalamus-pituitary-adrenal (HPA) axis activity. Following estradiol treatment, estradiol levels significantly increased only in substituted postmenopausal women (p < 0.001) reaching concentrations typically found in younger women during the follicular phase of the menstrual cycle. Corticosteroid-binding globulin levels did not differ significantly between groups. When confronted with the TSST, no response differences emerged between the three groups. However, estradiol treatment appeared to blunt the total plasma cortisol response in the Dex-CRH test, resulting in smaller increases in untreated premenopausal women and estradiol-treated postmenopausal women compared to placebo-treated postmenopausal women (p < 0.02). In sum, no response differences were observed after confrontation with a psychosocial stress test in our sample of healthy elderly subjects. As shown with the Dex-CRH test, our data suggest that the negative feedback of the HPA axis in elderly women is altered. Moreover, the current data suggest that estradiol replacement may modulate HPA feedback sensitivity in humans.

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Section: Discussionmentioning

confidence: 99%

Psychological and Endocrine Responses to Psychosocial Stress and Dexamethasone/ Corticotropin-Releasing Hormone in Healthy Postmenopausal Women and Young Controls: The Impact of Age and a Two-Week Estradiol Treatment

Kudielka¹,

Schmidt-Reinwald²,

Hellhammer³

et al. 1999

Neuroendocrinology

124

View full text Add to dashboard Cite

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“…For the interpretation of these data, it had to be taken into consideration as described above that the photoadduct did not contain a rCRFBP dimer and that one molecule of rCRFBP reacted with one molecule of the photoprobe. Together, these data indicated that the N-and C-terminal photophore groups of one photoprobe molecule reacted quantitatively with the same rCRFBP molecule at the two sites rCRFBP(34-38) and rCRFBP (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26).…”

Section: The Use Of Mics For the Characterization Of Photoadductsmentioning

confidence: 87%

“…Modified from ref. [6] probes because it represents the minimal sequence required for high-affinity binding to CRFBP and was introduced as the peptidic lead compound of a CRFBP inhibitor [10,15]. With the objective of generating different photoreactive analogs of h/rCRF 6-33 binding with high affinity to CRFBP, the N-and C-termini of this peptide were selected for introduction of the benzophenone (Bp) photophore on the basis of the knowledge derived from detailed structure-affinity relationship studies [13,15].…”

Section: Synthesis Of Benzophenone-derivatized Crf Analogsmentioning

confidence: 99%

“…Both digests were analyzed by the extraction of mass-selective MICs [12]. These MICs were generated on the basis of characteristic masses corresponding to the photoadduct fragments rCRFBP(34-38)X [Bp 6,32 ]h/rCRF 6-33 (6-8) and rCRFBP(12-26)X[Bp 6,32 ]h/ rCRF 6-33 (25-33) as well as to the photoprobe fragments [Bp 6,32 ]h/rCRF 6-33 (6-8), [Bp 6,32 ]h/rCRF (9)(10)(11)(12)(13)(14)(15)(16), and [Bp 6,32 ]h/rCRF 6-33 (25-33) (Fig. 5).…”

Section: The Use Of Mics For the Characterization Of Photoadductsmentioning

confidence: 99%

“…5). The presence of the internal photoprobe fragment [Bp 6,32 ]h/rCRF (9)(10)(11)(12)(13)(14)(15)(16) in both digests allowed scaling and, thus, semiquantitative comparison of the chromatograms. In agreement with the results obtained with the monofunctional photoprobes, the photoadduct fragments rCRFBP(34-38)X[Bp 6,32 ]h/rCRF (6)(7)(8) and rCRFBP(12-26)X[Bp 6,32 ]h/rCRF 6-33 (25-33) were detected in the digest of the photoadduct (Fig.…”

Section: The Use Of Mics For the Characterization Of Photoadductsmentioning

confidence: 99%

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Characterization of peptide?protein interactions using photoaffinity labeling and LC/MS

Jahn

Eckart

Tezval

et al. 2004

Analytical and Bioanalytical Chemistry

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The combination of photoaffinity labeling (PAL) with modern mass spectrometric techniques is a powerful approach for the characterization of peptide-protein interactions. Depending on the analytical strategy applied, a PAL experiment can provide different levels of information ranging from the identification of interaction partners to the structural characterization of ligand-binding sites. On the basis of LC/MS data generated in the framework of the identification of the binding site of the neuropeptide corticotropin-releasing factor (CRF) on its binding protein (CRFBP), the key role of LC/MS in the characterization of photoadducts on different structural levels was demonstrated. Covalent photoadducts of rat CRFBP (rCRFBP) were obtained by PAL with different mono- and bifunctional benzophenone photoprobes designed on the basis of the sequence of the synthetic CRF fragment human/rat CRF(6-33) which binds to CRFBP with high affinity. In view of the stoichiometry, LC/MS analysis revealed that the photoadducts consisted of one molecule of photoprobe and one molecule of rCRFBP. For a further characterization of the photoadducts on the oligopeptide level, enzymatic digests of unlabeled rCRFBP and of the respective photoadduct were compared by peptide mapping monitored with LC/MS. Thereby, it was found that the photoprobe that contained the photophore at its N-terminus labeled the amino acid sequence rCRFBP(34-38), whereas the photoprobe that contained the photophore at its C-terminus labeled rCRFBP(12-26). On the basis of the characterization of the photoadduct formed by rCRFBP and the bifunctional photoprobe that contained photophores on both termini, semiquantitative comparison of different enzymatic digests was accomplished by application of the mass-selective multiple ion chromatogram strategy.

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Distribution of urocortin-like immunoreactivity in the central nervous system of the rat

1998

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Urocortin was recently cloned from the rat midbrain. Urocortin is a member of the corticotropin releasing factor (CRF) peptide family and shows 45% sequence identity to CRF and 63% sequence identity to urotensin. It binds with a high affinity to CRF1 and CRF2 receptors, resulting in the stimulation of their adenylate cyclase activity. We used a polyclonal antibody against rat urocortin to define the distribution of urocortin-like immunoreactivity in the rat central nervous system. Several immunostained cell bodies were found in the supraoptic, paraventricular, and ventromedial hypothalamic nuclei. A large number of neurons with urocortin-like immunoreactivity were seen in the dorsolateral tegmental nucleus, in the linear and dorsal raphe nuclei, and in the substantia nigra. The most abundant immunoreactive (ir) perikarya were found in the Edinger-Westphal nucleus. Some neurons showed immunoreactivity in the interstitial nucleus of Cajal, the nucleus of Darkeschewitsch, and the periaqueductal gray. A dense immunoreactive fiber network was found in the lateral septal area. Some faintly stained axon terminals were observed among urocortin-ir perikarya in the supraoptic and paraventricular nuclei, in the central and periaqueductal gray, and in the Edinger-Westphal nucleus. No fibers with urocortin-ir were seen in the median eminence or the posterior pituitary. The distribution of urocortin-ir overlapped with the expression of the mRNA for the CRF2 receptor in several brain areas. These data support the hypothesis that this peptide is the endogenous ligand for the CRF2 receptor. Urocortin has been implicated in various endocrine responses, such as blood pressure regulation, as well as in higher cognitive functions.

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Ligand requirements of the human corticotropin-releasing factor-binding protein.

Cited by 104 publications

References 25 publications

Psychological and Endocrine Responses to Psychosocial Stress and Dexamethasone/ Corticotropin-Releasing Hormone in Healthy Postmenopausal Women and Young Controls: The Impact of Age and a Two-Week Estradiol Treatment

Psychological and Endocrine Responses to Psychosocial Stress and Dexamethasone/ Corticotropin-Releasing Hormone in Healthy Postmenopausal Women and Young Controls: The Impact of Age and a Two-Week Estradiol Treatment

Characterization of peptide?protein interactions using photoaffinity labeling and LC/MS

Distribution of urocortin-like immunoreactivity in the central nervous system of the rat

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