Biological Effects

Most of the endocrine, neurochemical, electrophysiological and behavioral effects which occur after intracerebral injection of CRF are comparable to those accompanying stress responses. These effects can be diminished or abolished by the administration of CRF antagonists. CRF is therefore considered to play a predominant role in the brain-pituitary-adrenal axis.

Besides a stimulatory effect of CRF on the secretion of ACTH, it also enhances the synthesis of proopiomelanocortin (the precursor of ACTH and several other opioidergic peptides). Furthermore, CRF is able to potentiate the effects of AVP and oxytocin upon the secretion of ACTH. CRF is also known to suppress the secretion of growth hormone (GH). This mechanism, however, seems to be indirect in nature since suppression of GH requires somatostatin.

Inhibitory effects of CRF on the secretion of the luteinizing hormone (LH) and gonadotropin-releasing hormone (GnRH) are further prominent functions of CRF.

The existence of direct synaptical connectivities between CRF-containing axons and dendrites of GnRH-containing neurons in the preoptic area of the rat led to the assumption that CRF influences directly the secretion or synthesis of GnRH.

A positive influence on the secretion of ^-endorphin and dynorphin has also been elucidated, as is the case for tyrosine hydroxylase (the enzyme which is necessary for the biosynthesis of norepinephrine) within the locus coeruleus.

In contrast to the stimulatory effect on catecholamines, CRF seems to have no effect upon the metabolism of GABA or serotonin.

CRF was also shown to produce a long-lasting potentiation of synaptic efficacy in neurons of the rat dentate gyrus in vivo; and it has been shown that CRF mRNA level in the dentate gyrus were significantly increased after LTP in vitro. These data suggest that CRF is capable of modulating hippocampal-depen-dent learning processes. By behavioral studies in which CRF was directly administered into the dentate gyrus of Sprague-Dawley rats, a memory-enhancing effect of CRF in the hippocampus has been documented.

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