The suppressive effects of prolonged administration of pharmacologic doses of glucocorticoids on the HPA function are wellknown and often represent a major problem in clinical practice: it is unknown after what duration of administration, and for what dosages of glucocorticoids precisely suppression of HPA function can be expected. A review of the literature discloses only a few definite answers to these questions as summarized in chapter I. However, it is certain that the HPA-axis is defined by a closed loop negative feedback system. The existence of corticotrophin releasing factors (CRF's) has been proved by a large amount of "circumstantial" evidence, but the exact nature of the main compound remained uncertain, until the recent isolation and characterization of an ovine CRF, which was a polypeptide of 41 aminoacids. It seems very probably however that other compounds will be detected which also exert CRF-like activity, and that not one "universal" CRF can be found. The evidence for the existence of a "short" loop negative feedback effect of ACTH on CRF release has been reviewed also in chapter 1 Most studies appeared in the late sixties and early seventies and almost all data were obtained from rats under very special circumstances, and the physiological implications of this phenomenon remained uncertain. The importance of neurotransmitters in the synthesis and release of CRF has been demonstrated convincingly by many authors. The existence of cholinergic and adrenergic pathways were known for a considerable time. The importance of serotonin as a stimulatory neurotransmitter gained increased attention in the last ten years. In this study our main aim was to determine whether stimulation of neurotransmitter activity with drugs might be able to enhance the HP A function to such extent that suppression by high circulating glucocorticoid levels could be prevented.

CRF, HPA function, corticotrophin releasing factors, glucocorticoids, hypothalamus
J.C. Birkenhäger (Jan) , S.W.J. Lamberts (Steven)
Erasmus University Rotterdam
Erasmus MC: University Medical Center Rotterdam

Janssens, E.N.W. (1984, May 16). Glucocorticoids and hypothalamo-pituitary-adrenal function : prevention of suppression?. Erasmus University Rotterdam. Retrieved from