CRF (6-33)

oCRF and CRF (6-33) depress food but not water intake in the obese Zucker rat.[Pubmed:10997635]

Int J Obes Relat Metab Disord. 2000 Jun;24 Suppl 2:S140-1.

It has previously been demonstrated that oCRF and the CRF binding protein inhibitor CRF (6-33) reduce body-weight gain in obese Zucker rats. We investigated whether the reduction in body-weight is attributable to altered feeding and drinking behaviour. Obese Zucker rats were fitted with osmotic mini-pumps connected to i.c.v. cannulas. Vehicle, oCRF (5 microg/day) or CRF (6-33) (25 microg/day) were infused for 7 days and the animals observed for an additional 7 days. Body-weight and food and water-intake were recorded daily at 14.00 h. In agreement with published results, oCRF and CRF (6-33) significantly reduced body-weight gain in the obese Zucker rat. In addition, food intake was reduced, whereas water consumption was unaffected.

The binding protein of corticotropin-releasing factor: ligand-binding site and subunit structure.[Pubmed:12215497]

Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12055-60.

Corticotropin-releasing factor (CRF), recognized as an important stress factor, binds to a CRF receptor and a CRF-binding protein (CRFBP) that represents a reservoir of endogenous CRF. Although CRFBP was observed to dimerize, at least in part, the ligand was found to be exclusively bound to the monomer-as indicated by photoaffinity labeling. We localized the CRF binding site by using photoaffinity labeling in combination with different mass spectrometric techniques. The amino acid residues Arg-23 and Arg-36 of CRFBP were identified as the sites of photoincorporation of monofunctional and bifunctional photoprobes designed on the basis of the amino acid sequence of human/rat CRF(6-33). It was, therefore, concluded that the sequence of amino acid residues 23-36 of CRFBP is involved in ligand binding. Our data are in support of an antiparallel alignment of the photoprobe with the amino acid residues 23-36 of the CRFBP monomer.

Dissociation of arousal-like from anxiogenic-like actions of brain corticotropin-releasing factor receptor ligands in rats.[Pubmed:11287075]

Behav Brain Res. 2001 Jul;122(1):43-50.

Behavioral actions of centrally administered corticotropin-releasing factor (CRF) are likely subserved by multiple brain targets and functional effector systems. The present studies compared effects of two CRF ligands, a full, post-synaptic CRF receptor agonist (rat/human CRF(1-41)) and a CRF binding protein ligand inhibitor (rat/human CRF(6-33)) in a behavioral testing battery sensitive to arousal, fear-like and aversive processes in Wistar rats. The profile of global efficacy for the centrally administered CRF receptor agonist was characterized by low dose (0.5-1.0 microg) arousal-like effects in locomotor and conditioned ambulation contexts and by high dose (5-25 microg) conditioned immobility, taste aversion and place aversion. In contrast, a profile of limited efficacy for the centrally administered CRF binding protein ligand inhibitor included only dose dependent motor activating and facilitation of fear conditioning effects without any of the anxiogenic-like or aversive properties of CRF agonist administration. These results suggest that arousal-like activation is a fundamental, physiologically relevant consequence of brain CRF system stimulation whereas aversive and anxiety-like effects reflect pharmacological actions of a CRF receptor agonist.

Selective stimulatory actions of corticotropin-releasing factor ligands on correlates of energy balance.[Pubmed:11564446]

Physiol Behav. 2001 Sep 1-15;74(1-2):5-13.

Acute administration of corticotropin-releasing factor (CRF) results in anorexic and sympathomimetic effects that suggest efficacy in chronic models of energy balance. The present studies employed a broad spectrum energy balance indices in lean and genetically obese Zucker rats in order to fully characterize the pharmacological efficacy of CRF and a CRF binding protein (CRF-BP) ligand inhibitor, CRF(6-33), which is thought to liberate CRF from CRF-BP. Acute administration of CRF(6-33) significantly increased CRF(2) receptor density by 10% within the ventromedial hypothalamic (VMH) nucleus of Zucker lean rats and decreased density by 10% in Zucker obese rats. A single infusion of CRF(6-33) increased nonshivering thermogenesis by 25-30% as measured by proton conductance in brown adipose tissue of both lean and obese rats. Chronic CRF(6-33) infusion suppressed body weight gain and elevated core temperature irrespective of genotype while increasing motor activity in obese rats without altering heart rate or blood pressure. Taken together, these results document strain-dependent, long-term effects of a CRF-BP ligand inhibitor on a select subset of physiological and behavioral measures of increased energy expenditure.