Endocrine Abstracts (2007) 13 P228

The novel broad-spectrum somatostatin receptor agonist SOM230 (Pasireotide), blocks the adrenalectomy-induced increase in mitotic activity in male rat anterior pituitary

Lesley Nolan1, Herbert Schmid2 & Andrew Levy1

1University of Bristol, Bristol, United Kingdom; 2Novartis Pharma AG, Basel, Switzerland.

The novel somatostatin receptor agonist SOM230 (pasireotide) binds with high affinity to somatostatin receptors sst1, sst2, sst3 and sst5. Acting principally through the latter, it inhibits basal and CRH-stimulated ACTH secretion from the AtT20 mouse corticotroph cell line and ACTH release from a proportion of human corticotroph adenomas both in vitro and in vivo. Data suggesting an additional antiproliferative effect has led to SOM230 being explored as a potential therapeutic alternative for patients with Cushing’s disease. We have examined the effects of SOM230 on adrenalectomy-induced mitotic and apoptotic activity in the male rat anterior pituitary.

Adrenalectomized and sham-adrenalectomized Wistar rats were treated with daily subcutaneous injection of vehicle or SOM230 (30 μg at surgery followed by 60 μg/day thereafter). Changes in mitotic and apoptotic index as a percentage of total anterior pituitary cells were derived by direct identification, and computer-assisted quantification in 2 μm-thick haemotoxylin and eosin-stained pituitary sections obtained 2, 4 and 6 days post-operatively.

SOM230 completely blocked the wave of increased mitotic activity normally seen in the anterior pituitary after adrenalectomy, but did not prevent the expected increase in the number of ACTH-immunopositive cells. Interestingly, SOM230 did not suppress baseline pituitary cell turnover in sham-operated animals. There were no measurable effects on apoptotic rate in any group.

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