To determine the inhibitory profile of the novel
somatostatin (SRIF) analog
SOM230 with broad SRIF receptor binding, we compared the in vitro effects of
SOM230,
octreotide (OCT), and SRIF-14 on
hormone release by cultures of different types of secreting
pituitary adenomas. OCT (10 nM) significantly inhibited GH release in seven of nine
GH-secreting pituitary adenoma cultures (range, -26 to -73%),
SOM230 (10 nM) in eight of nine cultures (range, -22 to -68%), and SRIF-14 (10 nM) in six of six cultures (range, -30 to -75%). The sst analysis showed predominant but variable levels of
somatostatin receptor (sst)(2) and sst(5)
mRNA expression. In one culture completely resistant to OCT,
SOM230 and SRIF-14 significantly inhibited GH release in a dose-dependent manner with an IC(50) value in the low nanomolar range. In the other cultures,
SOM230 showed a lower potency of GH release inhibition (IC(50), 0.5 nM), compared with OCT (IC(50), 0.02 nM) and SRIF-14 (IC(50), 0.02 nM). A positive correlation was found between sst(2) but not sst(5)
mRNA levels in the
adenoma cells and the inhibitory potency of OCT on GH release in vivo and in vitro, and the effects of
SOM230 and SRIF-14 in vitro. In three
prolactinoma cultures, 10 nM OCT weakly inhibited
prolactin (PRL) release in only one (-28%), whereas 10 nM
SOM230 significantly inhibited PRL release in three of three cultures (-23, -51, and -64.0%). The inhibition of PRL release by
SOM230 was related to the expression level of sst(5) but not sst(2)
mRNA. Several conclusions were reached. First,
SOM230 has a broad profile of inhibition of tumoral pituitary
hormone release in the low nanomolar range, probably mediated via both sst(2) and sst(5) receptors. The higher number of responders of
GH-secreting pituitary adenoma cultures to
SOM230, compared with OCT, suggest that
SOM230 has the potency to increase the number of acromegalic patients which can be biochemically controlled. Second, compared with OCT,
SOM230 is more potent in inhibiting PRL release by mixed GH/PRL-secreting
adenoma and
prolactinoma cells.