Differential penetration of three anterior pituitary peptide hormones into the cerebrospinal fluid of rhesus monkeys

Abstract

This paper demonstrates marked differences between blood levels and those in the CSF for three anterior pituitary peptide hormones, prolactin, luteinizing hormone (LH) and adrenocorticotrophin (ACTH) in the rhesus monkey. CSF levels of endogenous prolactin (measured by radioimmunoassay) are about 20% of those in the blood, and this proportion remains constant under conditions of persistent (‘steady-state’) hyperprolactinaemia (induced by injecting sulpiride). Acutely elevating prolactin, by either an intravenous injection of exogenous ovine prolactin, or sulpiride, resulted in similar rates of entry by prolactin into the CSF, suggesting that retrograde portal flow is not an important mechanism. LH, measured by bioassay, is also present in the CSF, but the CSF/blood ratio is 5–10 time less than for prolactin. Castration, causing blood LH levels to rise, resulted in equivalent changes in CSF, so that the ratio remains constant, though still much lower than for prolactin. There are significant correlations between individual animals in the blood and CSF content of prolactin and LH. In marked contrast, whilst ACTH is found (by cytochemical assay) in the CSF of both intact and adrenalectomized monkeys, no significant change in CSF levels occurs despite 10-fold changes in the plasma of adrenalectomized animals following withdrawal of cortisol. Nor is there any correlations between blood and CSF ACTH levels over a wide range of concentrations. These results show that each of the three peptides studied has a distinct pattern of entry into the CSF from the vascular compartment. There are neural systems within the brain which are thought to contain peptides similar to those secreted by the anterior pituitary gland (1). If these peptides can reach the brain from the pituitary, it follows that peptide-sensitive sites may be controlled not only by direct neural action but also by an external endocrine source. How can specifity of neuronal control be maintained in this unusual situation? The distribution of peptide hormones between cerebral and vascular compartments is consequently of great interest, hormone leves in the cerebrospinal fluid (CSF) providing a guide to the concentrations to which neural tissues are exposed (2). It has been suggested that hormones from the anterior pituitary may enter the brain directly by retrograde transport in the portal vessels connecting the two structures (3, 4). If this were so, peptides which otherwise have difficulty in crossing the blood brain barrier might gain privileged access to the brain. We have studied the levels of three anterior pituitary hormones, prolactin, adrenocorticotrophin (ACTH) and luteinizing hormone (LH) in the blood and CSF of rhesus monkeys studied under a variety of conditions. We have found that, whilst all three can be detected in the CSF, relationships between levels there and those in the blood were quite distinct for each hormone. Prolactin reaches the CSF from the peripheral circulation in relatively large amounts and CSF levels are critically dependent upon those in blood. LH, on the other hand, whilst also entering the CSF in amounts correlated with those in the blood, is represented proportionately in the CSF much less than prolactin. Levels of ACTH in the CSF, in marked contrast, were unrelated to those in the blood and were unaltered by changing levels in the vascular compartment.