SOMATOSTATIN RECEPTOR MANIPULATION

The expression of somatostatin receptors (ssts) on human tumours is th e basis for the successful therapeutic and diagnostic application of(r adiolabelled) somatostatin analogues. Manipulation (up-regulation) of sst expression might improve the uptake of radioligand in in vivo scin tigraphy of human sst-positive tumours, as well as the potential succe ss of radiotherapy using radiolabelled SRIF analogues. In clonal pitui tary cell lines, agonist exposure (SRIF-14, SRIF-28, octreotide) has b een shown to either reduce or increase sst (subtype) expression, sugge sting cell-type-specific responsiveness. In addition, glucocorticoids and oestrogens were shown to down- and up-regulate, respectively, sst numbers. So far, little information is available with respect to sst ( subtype) regulation in non-pituitary-derived cell types. We have found that sst expression in the model of the transplantable prolactin (PRL )-secreting rat pituitary tumour 7315b is mainly dependent upon the pr esence of oestradiol (E(2)), both in vivo and in vitro. This tumour is sst negative in vivo. In vitro, the addition of E(2) induces sst expr ession (sst(2) and sst(3) subtypes). The in vivo administration of E(2 ) (20 mu g/day subcutaneously) to 7315b-tumour-bearing rats induces ss t(2) mRNA expression. The absence of sst expression in 7315b tumours i n vivo may be due to the inhibition of ovarian E(2) production by the high circulating PRL levels in the 7315b-prolactinoma-bearing rats. In deed, no detectable E(2) levels were found in the serum of 7315b-tumou r-bearing rats. Taken together, our data suggest that the 7315b rat pr olactinoma can indirectly manipulate (down-regulate) its own sst expre ssion, in vivo, via its host. This experimental 7315b prolactinoma mod el might be representative for most untreated female prolactinoma pati ents. Clinically, patients with microprolactinomas do not benefit from octreotide treatment.