Synthetic competitive antagonists of corticotropin-releasing factor: effect on ACTH secretion in the rat

Polypeptide analogs of the known members of the corticotropin-releasing factor (CRF) family were synthesized and tested in vitro and in vivo for enhanced potency or competitive antagonism. Predictive methods and physicochemical measurements had suggested an internal secondary alpha-helical conformation spanning about 25 residues for at least three members of the CRF family. Maximization of alpha-helix-forming potential by amino acid substitutions from the native known sequences (rat/human and ovine CRF, sauvagine, and carp and sucker urotensin 1) led to the synthesis of an analog that was found to be more than twice as potent as either of the parent peptides in vitro. In contrast, certain amino-terminally shortened fragments, such as alpha-helical CRF or ovine CRF residues 8 to 41, 9 to 41, and 10 to 41, were found to be competitive inhibitors in vitro. Selected antagonists were examined and also found to be active in vivo.     

Interleukin-1 stimulates the secretion of hypothalamic corticotropin-releasing factor

There is now evidence that the immune system, during times of infectious challenge, can stimulate the secretion of glucocorticoids, the adrenal steroids that mediate important aspects of the response to stress. Specifically, secretion of interleukin-1 (IL-1), a monocyte lymphokine secreted after infection, appears at least in part responsible for this effect. Glucocorticoids are secreted in response to a neuroendocrine cascade involving, first, the brain, then the pituitary, and finally the adrenal gland. In this report, human IL-1 is shown to activate the adrenocortical axis at the level of the brain, stimulating the release of the controlling hormone corticotropin-releasing factor (CRF) from the hypothalamus. Infusion of IL-1 induced a significant secretion of CRF into the circulation exiting the hypothalamus, whereas immunoneutralization of CRF blocked the stimulatory effect of IL-1 on glucocorticoid secretion. IL-1 appeared to have no acute direct stimulatory effects on the pituitary or adrenal components of this system. Furthermore, IL-1 did not cause a nonspecific release of other hypothalamic hormones. Thus, the lymphokine acts in a specific manner to activate the adrenocortical axis at the level of the brain; this effect appears to be unrelated to the known pyrogenic effects of IL-1 within the hypothalamus.     

Barley—Pyrenophora graminea interaction: QTL analysis and gene mapping

Pyrenophora graminea is a seed-borne pathogen and is the causal agent of the barley leaf stripe disease. Our aim is to study the genetic basis of barley resistance to leaf stripe. A qualitatively acting resistance factor has been identified in the cultivar ‘Vada’ and the partial resistance of the cultivar ‘Proctor’ to a P. graminea isolate has been demonstrated to be dominated by a major quantitative trait locus (QTL), mapped on barley chromosome 1. Map colinearity between the leaf stripe ‘Proctor’ resistance QTLs,‘Vada’ resistance to leaf stripe, and other disease resistance loci have been investigated in this work using molecular markers. Moreover, since inoculation of barley rootlets by the fungus had been shown to induce the accumulation of several PR (pathogen-related) mRNA families, seven barley PR genes have been mapped as RFLPs, and one assigned to a chromosome arm via ditelosomic analysis to verify possible map associations with resistance QTLs. This work discusses the genetic relationships between the known leaf stripe resistance loci, resistance loci towards other seed-borne pathogens and defence gene loci.