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 Cushings 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.