Stimulatory effect of SOM230 on human and rat adrenal corticosteroid secretion in vitro.
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.
Department of Medical Sciences, University of Milan, Italy. fpg@auxologico.it
F
F
Pecori Giraldi
L
L
Pagliardini
M F
MF
Cassarino
F
F
Martucci
A
A
Sesta
L
L
Castelli
E
E
Montanari
H A
HA
Schmid
F
F
Cavagnini
D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003345:Corticosterone / Q000378:metabolism*; D006801:Humans; D051381:Rats; D013004:Somatostatin / Q000819:agonists / Q000031:analogs & derivatives* / Q000494:pharmacology
D013004:Somatostatin; C517782:pasireotide; D003345:Corticosterone