DIFFERENTIAL ALPHA-1 AND ALPHA-2 ADRENERGIC EFFECTS ON HYPOTHALAMIC CORTICOTROPIN-RELEASING FACTOR AND PLASMA ADRENOCORTICOTROPIN

There is presently no consensus as to the nature of the catecholaminergic influence on the regulation of corticotropin-releasing factor. The potential role that the alpha-adrenergic system plays was investigated by measuring hypothalamic corticotropin-releasing factor-like immunoreactivity and plasma adrenocorticotropin, following manipulation of alpha-1 and alpha-2 adrenergic receptor activation. Administration of the alpha-1 agonist methoxamine did not significantly alter either plasma adrenocorticotropin or hypothalamic corticotropin-releasing factor. Administration of the alpha-2 agonist clonidine resulted in a 24-fold increase in plasma adrenocorticotropin and a significant decrease in median eminence corticotropin-releasing factor, consistent with its release. Corticotropin-releasing factor in the remainder of the hypothalamus was not altered. Concurrent administration of clonidine with the selective alpha-2 antagonist yohimbine prevented the clonidine-induced changes in plasma adrenocorticotropin and hypothalamic corticotropin-releasing factor, consistent with the clonidine effect being mediated through alpha-2 receptors. Concurrent administration of clonidine with methoxamine did not prevent these effects, suggesting that the effect of clonidine was not mediated through presynaptic inhibition of noradrenergic-adrenergic neurotransmission. Inhibition of protein synthesis by anisomycin induced changes in corticotropin-releasing factor and adrenocorticotropin which were not altered by combined treatment with methoxamine or clonidine. These data suggest differential roles for alpha-1 and alpha-2 systems in the regulation of corticotropinreleasing factor. Results from alpha-2 adrenergic activation were consistent with stimulation of corticotropin-releasing factor release, an effect mediated by a postsynaptic alpha-2 mechanism. These data also suggest a near-maximal alpha-1 adrenergic effect exists physiologically which topically maintains corticotropin-releasing factor concentrations in hypothalamus by either stimulation of synthesis or inhibition of release. © 1990.