Somatostatin receptor manipulation.
The expression of somatostatin receptors (ssts) on human tumours is the basis for the successful therapeutic and diagnostic application of (radiolabelled) somatostatin analogues. Manipulation (up-regulation) of sst expression might improve the uptake of radioligand in in vivo scintigraphy of human sst-positive tumours, as well as the potential success of radiotherapy using radiolabelled SRIF analogues. In colonal pituitary cell lines, agonist exposure (SRIF-14, SRIF-28, octreotide) has been shown to either reduce or increase sst (subtype) expression, suggesting 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 presence of oestradiol (E2), both in vivo and in vitro. This tumour is sst negative in vivo. In vitro, the addition of E2 induces sst expression (sst2 and sst3 subtypes). The in vivo administration of E2 (20 micrograms/day subcutaneously) to 7315b-tumour-bearing rats induces sst2 mRNA expression. The absence of sst expression in 7315b tumours in vivo may be due to the inhibition of ovarian E2 production by the high circulating PRL levels in the 7315b-prolactinoma-bearing rats. Indeed, no detectable E2 levels were found in the serum of 7315b-tumour-bearing rats. Taken together, our data suggest that the 7315b rat prolactinoma can indirectly manipulate (down-regulate) its own sst expression, in vivo, via its host. This experimental 7315b prolactinoma model might be representative for most untreated female prolactinoma patients. Clinically, patients with microprolactinomas do not benefit from octreotide treatment.
Visser-Wisselaar
H A
HA
Department of Internal Medicine III, Erasmus University, Rotterdam, The Netherlands.
Hofland
L J
LJ
van Uffelen
C J
CJ
van Koetsveld
P M
PM
Lamberts
S W
SW
D000818:Animals; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D010911:Pituitary Neoplasms / Q000378:metabolism; D015175:Prolactinoma / Q000378:metabolism; D051381:Rats; D017481:Receptors, Somatostatin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology*
D006727:Hormone Antagonists; D017481:Receptors, Somatostatin; D013004:Somatostatin