Relationship between adrenocorticotrophin bioactivity in blood and cerebrospinal fluid of rhesus monkeys

Abstract

Adrenocorticotrophin levels, measured by a cytochemical bioassay, were determined in the plasma and cerebrospinal fluid (CSF) of adult female rhesus monkeys which were ovariectomized and receiving oestrogen replacement therapy. In control monkeys, ACTH bioactivity was found in both CSF (10.2 +/- 1.8 ng/l) and plasma (186 +/- 51 ng/l) in samples taken at 14.00 h (lights on: 07.00-19.00 h). Dexamethasone treatment (0.2 mg/kg) twice daily for 4 days suppressed plasma ACTH levels (52.8 +/- 25.2 ng/l) but had no effect on CSF levels (7.6 +/- 2.7 ng/l). Raising plasma ACTH, either by daily injections of a long-acting preparation of ACTH (1-24) for 6 days or by bilateral adrenalectomy (and subsequently with-drawing cortisol replacement therapy) also resulted in no detectable changes in ACTH levels in the CSF. A regression analysis between ACTH in the plasma and CSF from samples taken throughout the experiments showed no correlation. In contrast, measurement of ACTH by radioimmunoassay, whilst satisfactory for determination of this peptide in plasma, could not identify authentic ACTH in the CSF. It is concluded that bioactive ACTH does not enter the CSF in detectable quantities from either the peripheral vascular compartment or from the animal's own pituitary gland, and that reducing ACTH secretion from the pituitary also has no effect on levels of ACTH in the CSF. This is in marked contrast to other pituitary peptide hormones, including prolactin, which is secreted together with ACTH during 'stress' but which, unlike ACTH, enters the CSF relatively easily.

Treatment of Infantile Spasms

“…Finally, it is uncertain how systemic ACTH exerts effects within the brain since the blood-brain barrier is relatively impermeable to ACTH. 34 Spinal fluid ACTH derives largely from ACTH released by pro-opiomelanocortin-positive neurons of the arcuate nucleus of the hypothalamus and proopiomelanocortin-positive neurons of the nucleus tractus solitarius of the medulla. Cerebrospinal fluid ACTH levels are low in untreated infantile spasms, [35][36][37][38] suggesting deficient synthesis within the brain of ACTH and the related endogenous peptide, a-melanocyte-stimulating hormone.…”

Effects of Acute Confinement Stress-induced Hypothalamic-pituitary Adrenal Axis Activation and Concomitant Peripheral and Central Transforming Growth Factor-β1 Measures in Nonhuman Primates

“…However, those studies compared adrenocorticotrophin levels in the plasma and CSF. 36,37 We have previously reported a strong positive relationship between peripheral cortisol and TGF-β1 levels under conditions of acute restraint stress. 14 This study differs from the study of Smith et al.…”

“…The divergent response observed in serum and CSF TGF-β1 in the current study are in keeping with prior studies in rhesus macaques showing differential physiological response in CNS versus the periphery. However those studies compared adrenocorticotrophin levels in the plasma and CSF 36, 37 . We have previously reported a strong positive relationship between peripheral cortisol and TGF-β1 levels under conditions of acute restraint stress 14 .…”