Effect of the slow-release formulation of somatuline (BIM 23014) on estrogen-induced hyperprolactinemia and lactotroph hyperplasia in the female rat.
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 beta E2) in rats. Female rats were primed with 17 beta E2 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 beta E2-primed rats and 23.58 +/- 1.26 mg in 17 beta E2-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 beta E2-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 beta E2-induced increase in PRL cell density was also reduced by somatuline treatment. We conclude that the slow-release formulation of somatuline impedes 17 beta E2-induced hyperprolactinemia and pituitary enlargement concomittantly, at least in part by acting on lactotroph proliferation.
Schussler
N
N
Unité INSERM 223, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Farnoud
R
R
Rauch
C
C
Roche
M
M
Berthet
M
M
Thomas
F
F
Peillon
F
F
Bayet
M C
MC
D000818:Animals; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007273:Injections, Intramuscular; D015282:Octreotide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D009929:Organ Size; D010456:Peptides, Cyclic; D010903:Pituitary Gland, Anterior / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D011388:Prolactin / Q000097:blood / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013004:Somatostatin / Q000031:analogs & derivatives*
D003692:Delayed-Action Preparations; D010456:Peptides, Cyclic; C060347:lanreotide; D004958:Estradiol; D013004:Somatostatin; D011388:Prolactin; D015282:Octreotide