LOCALIZATION OF PARATHYROID HORMONE-RELATED PEPTIDE (PTHRP) AND PTH PTHRP RECEPTOR MESSENGER-RNAS IN RAT-BRAIN/

Parathyroid hormone (PTH)-related peptide (PTHrP) has been identified in human tumors associated with the syndrome of humoral hypercalcemia of malignancy. PTHrP mRNA is also expressed in a variety of non-malign ant tissues, suggesting that PTHrP is an endogenous peptide with as-ye t unidentified autocrine or paracrine functions in normal tissues, inc luding brain (Weir et al., Proc. Natl. Acad. Sci., 87 (1990) 108-112). In the present study, we used in situ hybridization to examine the ex pression of PTHrP and the common receptor for PTH and PTHrP in adult r at brain. Widespread yet anatomically discrete patterns of hybridizati on were observed using S-35-labeled antisense cRNA probes. PTHrP gene expression was highest in the supramamillary nucleus of the hypothalam us, medial superior olivary nucleus, and in subpopulations of cells in the neostriatum, hippocampus, and cerebral cortex. Other major sites of PTHrP gene expression included the amygdala, midline thalamic nucle i, pontine nuclei, choroid plexus, and the anterior pituitary gland. H ighest levels of PTH/PTHrP receptor mRNA were in the mesencephalic por tion of the trigeminal nucleus and the trigeminal ganglion, the latera l reticular, pontine and reticulotegmental nuclei, the hypoglossal nuc leus and area postrema. Other major sites of PTH/PTHrP receptor expres sion included the anterodorsal nucleus of the thalamus, basolateral am ygdala, entorhinal cortex, parasubiculum, cells in the Purkinje cell l ayer of the cerebellum, vestibular nuclei, ventral cochlear nucleus, t he motor nucleus of the trigeminal, and the facial and external cuneat e nuclei. The expression of genes encoding PTHrP and its receptor in d iscrete areas of the brain suggests that PTHrP may function as a neuro transmitter in the central nervous system.