Effect of the slow-release formulation of somatuline (BIM 23014) on estrogen-induced hyperprolactinemia and lactotroph hyperplasia in the female rat

Abstract

Somatuline, in common with other SRIH analogues, exerts antiproliferative and antisecretory activities on various tumors. Our purpose was to test the effectiveness of a slow-release formulation of somatuline on lactotroph hyperplasia and PRL hypersecretion induced by estrogens (17 βE 2) in rats. Female rats were primed with 17 βE 2 for 6 weeks before receiving somatuline (2 mg/kg) intramuscular injections every 10 days for one month. The mean anterior pituitary weight was 11.22 ± 0.32 mg (mean ± SEM) in non-estrogenized rats, 29.62 ± 1.63 mg in 17 βE 2-primed rats and 23.58 ± 1.26 mg in 17 βE 2-primed somatuline-treated rats. Mean plasma PRL level was 5.63 ± 0.97 ng/ml, 182.37 ± 27.55 ng/ml and 113.89 ± 15.07 ng/ml in the same groups respectively. Thus, the 17 βE 2-induced pituitary enlargement and hyperprolactinemia were 20% and 38% lower respectively when animals were treated with somatuline during the last month of estrogenization. The 17 βE 2-induced increase in PRL cell density was also reduced by somatuline treatment. We conclude that the slow-release formulation of somatuline impedes 17 βE 2-induced hyperprolactinemia and pituitary enlargement concomittantly, at least in part by acting on lactotroph proliferation.