Increase of corticotropin-releasing factor staining in rat paraventricular nucleus neurones by depletion of hypothalamic adrenaline

Abstract

In response to stress, adrenocorticotropic hormone (ACTH) is released by corticotrophs in the anterior pituitary under the control of several central and peripheral factors^1,2 including corticotropin-releasing factor (CRF), which was recently isolated from the brain and sequenced³. Immunocytochemical studies have shown that most of the CRF-containing cell bodies that project to the median eminence are present in the hypothalamic paraventricular nucleus (PVN)^4–6. A dense PNMT(phenylethanolamine-N-methyltrans-ferase)-containing fibre network was also observed in the same region^7,8—PNMT is the final enzyme in the biosynthesis of adrenaline9 and has been demonstrated in the brain¹⁰. In the present study we found an association of adrenergic nerve fibres and CRF neurones by immunohistochemistry using antisera to PNMT and CRF. To examine the functional significance of the adrenergic projection to the PVN, we blocked the synthesis of adrenaline using a specific inhibitor of PNMT. The depletion of adrenaline resulted in an increase in CRF immunoreactivity. The present results suggest that, as well as catecholamines which regulate ACTH release at the anterior pituitary level via a β₂-adrenergic receptor mechanism⁹, central catecholamines (mainly adrenaline) also affect ACTH release through their action on CRF cells. Peripheral catecholamines seem to have a direct stimulatory effect on the pituitary corticotroph cells¹¹, whereas the present findings suggest that central adrenaline-containing neurones have an inhibitory role in the physiological response to stress.