Effects of the Somatostatin Analog BIM 23014 on the Secretion of Growth Hormone, Thyrotropin, and Digestive Peptides in Normal Men

Abstract

BIM 23014 (BIM) is a long-acting octapeptide somatostatin analog. We studied the effects of this analog on the secretion of GH, TSH, and gastroenteropancreatic hormones [secretin, motilin, and pancreatic polypeptide (PP)] in normal men. In the first protocol three BIM doses (125, 250, and 500 micrograms) and vehicle were administered sc in random order at 2000 h to eight normal young men. Plasma GH concentrations decreased during the first part of the night only after the highest dose (P less than 0.05). Plasma secretin levels did not change, while plasma motilin decreased after the 250- and 500-micrograms doses (P = 0.05 and P = 0.02, respectively), and plasma PP decreased after all three doses (P less than 0.05, P less than 0.01, and P less than 0.01, respectively) during the first part of the night. In the second protocol, eight men received BIM, administered by constant sc infusion during the night in a dose of 2 mg/12 h, or vehicle, either alone or in association with a 10 ng/kg.min iv GHRH or vehicle infusion. Nocturnal GH secretion was suppressed by the BIM infusion (P less than 0.001). GH secretion, stimulated by GHRH infusion (P less than 0.001), was reduced by concomitant BIM infusion (P less than 0.001) and was pulsatile during the combined infusions. BIM infusion suppressed the physiological nighttime rise in plasma TSH levels. Plasma motilin and PP levels were reduced by BIM, when administered either alone or in combination with GHRH. We conclude that: 1) BIM is capable of reducing GH secretion when administered sc in a dose of 500 micrograms and of abolishing nocturnal GH secretion when constantly infused at a dose of 2 mg/12 h; 2) BIM, constantly infused, reduces the nocturnal rise in TSH secretion; and 3) motilin and PP secretion are more sensitive than that of GH to BIM, as they are reduced by a lower dose.

Pulsatile growth hormone secretion persists in genetic growth hormone-releasing hormone resistance

“…Pulsatility of GH secretion has been observed, albeit at varying amplitudes, under most, if not all, experimental conditions, including infusions with GHRH (72,79), GHS (27,32,35), and somatostatinergic agents (7,13,61) alone or in combination (61), GHRH antagonist treatment (34), and now, genetic GHRH resistance. Thus, pulsatility appears as a very robust feature of GH secretion that persists despite attempts to disrupt hypothalamic input.…”

“…Additional complexities are imposed by nutritional status, sex steroid milieu, and feedback by insulin-like growth factor (IGF) I and GH. In humans, where hypophysial-portal sampling is not feasible, the roles of GHRH and somatostatin have been inferred from studies with continuous, presumably saturating infusions of GHRH, GHS, and somatostatin or its analogs (7,13,32,35,61,72,79) as well as by the use of a GHRH antagonist (33,34). These studies have provided evidence for a predominant role of GHRH and an additive role of somatostatin in GH pattern regulation in humans.…”

Long-term treatment of acromegaly with the slow-release somatostatin analogue lanreotide

“…In previous studies BIM 23014 proved to be a useful tool in selectively inhibiting GH secretion (1)(2)(3). The effects of the slow-release formulation of the product have been reported in a limited number of patients with treatment period not exceeding 12 months (4-6).…”

An Open, Phase III Study of Lanreotide(Somatuline PR) in the Treatment of Acromegaly.

“…Lanreotide, a long acting analogue of somatostatin, binds preferentially to pituitary somatostatin receptors [16], to inhibit GH secretion in healthy men [17]. Lanreotide has an increased potency for growth hormone inhibition and a prolonged plasma half life compared with the An antiproliferative effect of lanreotide has been shown in vitro on several tumour cell lines.…”