SOM230 (
pasireotide, Signifor), a recently developed
somatostatin analog, has been tested in
ACTH-secreting
pituitary tumors with promising results. No study has yet evaluated whether this analog also directly affects adrenal
steroid production. The aim of the current study was to evaluate whether
SOM230 modulates
corticosteroid secretion by normal adrenals in vitro. Primary cultures from normal human and rat adrenals were incubated with 10-100 nM
SOM230 with and without 10nM
ACTH. Dose-response studies with 1 nM-1 μM
SOM230 were performed on rat adrenals.
Cortisol/
corticosterone levels in medium were measured after 4 and 24h.
SOM230 (10nM) significantly increased
corticosteroid levels after 24h incubation in both human (36.4 ± 0.43 ng/well vs 27.7 ± 3.17 ng/well, p<0.05) and rat (16.2 ± 1.16 ng/well vs 11.6 ± 0.92 ng/well p<0.05) adrenals; lesser effects were observed with 100 nM SOM (33.4 ± 2.59 ng/well vs 27.7 ± 3.17 ng/well p<0.05; 13.4 ± 0.82 ng/well vs 11.6 ± 0.92 ng/well, N.S. vs baseline secretion for human and rat adrenals, respectively). Dose-response curves confirmed maximal effect at 10nM
SOM230. The
corticosteroid secretory response to
ACTH was unaffected by
SOM230 co-incubation. In conclusion,
SOM230 exerts a moderate stimulatory effect on adrenal
corticosteroid secretion in vitro. This argues against a direct adrenal involvement in the clinical efficacy of
SOM230 in patients with
ACTH-secreting
pituitary tumors and widens the known range of action of
SOM230.