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STIMULATORY EFFECT OF SOM230 ON HUMAN AND RAT ADRENAL CORTICOSTEROID SECRETION IN VITRO

Schmid, Herbert and Giraldi Pecori, F and Pagliardini, L and Cassarino, F and Martucci, F and Castelli, L and Montanari, E and Cavagnini, F (2012) STIMULATORY EFFECT OF SOM230 ON HUMAN AND RAT ADRENAL CORTICOSTEROID SECRETION IN VITRO. General Comp Endocrinology.

Abstract

Context: SOM230 (pasireotide, Signifor), a recently developed somatostatin analogue, has been tested in patients with Cushing’s disease with promising results. Experimental evidence indicates a pituitary site of action but no study has yet evaluated whether this analogue also directly affects adrenal steroid production.
Objective: Aim of the current study was to evaluate whether SOM230 modulates corticosteroid secretion by normal adrenals in vitro.
Design, intervention and outcomes: primary cultures from 6 normal human adrenals and 10 rat adrenals were incubated with 10 - 100 nM SOM230 with and without 10 nM 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 24 hours.
Results: 10 nM SOM230 significantly increased corticosteroid levels after 24h incubation in both human (131.4 ± 1.55% of baseline, p<0.05 vs unchalled wells) and rat (138.1 ± 10.21%, p<0.05) adrenals; lesser effects were observed with 100 nM SOM (120.4 ± 9.33% p<0.05; 117.3 ± 15.49% N.S., for human and rat adrenals, respectively). Dose-response curves confirmed maximal effect at 10 nM SOM230. The corticosteroid secretory response to ACTH was unaffected by SOM230 co-incubation.
Conclusions: SOM230 exerts a moderate stimulatory effect on adrenal corticosteroid secretion in vitro. This argues against a direct adrenal inhibitory effect of SOM230 in patients with Cushing’s syndrome.

Item Type: Article
Date Deposited: 07 May 2016 23:45
Last Modified: 07 May 2016 23:45
URI: https://oak.novartis.com/id/eprint/5192

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