Demonstration of parathyroid hormone-related protein in meninges and its receptor in astrocytes: evidence for a paracrine meningo-astrocytic loop.

In contrast to the nervous and glial tissue of the adult rat brain the meninges are immunoreactive for parathyroid hormone-related protein (PTHrP), a hormone that binds with high affinity to the recently cloned PTH/PTHrP receptor. Accordingly immunoreactivity is found in cultured meningeal cells but not in astrocytes. In contrast, astrocytes but not meningeal cells synthesize the mRNA for the PTHrP receptor shown by reverse transcription of total RNA preparations and subsequent polymerase chain reaction with primers specific for the PTHrP receptor. The expression of the PTH/PTHrP receptor was confirmed by the dose-dependent activation of the adenylate cyclase in astrocytes and the rapid development of cellular processes following on incubation with PTHrP. We conclude that PTHrP secreted by meninges forms a paracrine meningo-astrocytic loop and may cause astrocytic differentiation, possibly involved in the formation of the glial limiting membrane.