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Endocrine Abstracts (2003) 5 P186

BES2003 Poster Presentations Neuroendocrinology and Behaviour (16 abstracts)

Effect of the novel somatostatin ligand, SOM230, on rat & human anterior pituitary hormone secretion

RD Murray 1 , K Kim 1 , SG Ren 1 , G Weckbecker 2 , C Bruns 2 & S Melmed 1

1Cedars Sinai Research Institute, UCLA School of Medicine, Los Angeles, USA; 2Novartis Pharma AG, Basel, Switzerland.

The clinically available somatostatin (SRIF) analogues, octreotide and lanreotide, are the mainstay of treatment for patients with acromegaly in whom surgery has failed to adequately control GH and IGF-I levels or where surgery is contra-indicated. Both analogues exhibit selective high affinity for SRIF receptor subtype 2 (SSTR2). GH and TSH secretion are regulated by SSTR subtypes 2 & 5, with an additional effect on GH secretion via SSTR1. Prolactin is regulated by SSTR5 alone. It is foreseeable that a SRIF analogue with universal high affinity SSTR binding such as SOM230 will not only have greater efficacy for GH inhibition, but also regulate secretion of additional anterior pituitary hormones.
In primary cultures of rat pituitary cells incubation for 20 hours with 10 nM SRIF14, octreotide, and SOM230 resulted in a 16, 35, and 26% inhibition of prolactin secretion respectively. TSH and LH secretion were inhibited 76 & 50% by SOM230, 61 & 34% by octreotide, and 45 & 14% by SRIF14 respectively. In primary cultures of human foetal pituitary cells TSH release was inhibited similarly by both SOM230 and octreotide respectively.
In primary cultures 10 nM SOM230 was more effective in inhibiting PRL release from two PRL-secreting adenoma than octreotide. The mean inhibition of PRL secretion by SOM230 was 35%, and by octreotide, 22%. Using RT-PCR, both tumours were shown to express SSTR1 & SSTR2; the tumour that responded with greater reduction in PRL secretion additionally expressed SSTR5. In three cultured clinically non-functioning glycoprotein-secreting adenoma the mean reduction in alpha-subunit secretion following incubation with 10 nM SOM230 or octreotide was 46 & 24% respectively. All three tumours expressed SSTR2 by RT-PCR, and one tumour additionally expressed SSTR3.
SOM230 effectively inhibits GH secretion both in-vivo and in-vitro. These results provide a rationale that SOM230, in addition to treating patients with acromegaly, may be of value in treating non-GH secreting pituitary adenoma types.

Volume 5

22nd Joint Meeting of the British Endocrine Societies

British Endocrine Societies 

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