Hormonal Control of Rat Fetal Pancreas Development

Abstract

Rat fetal pancreas development and maturation were investigated in vitro and in vivo, and the informations available on their controls do not agree. Our main objective was to reinvestigate fetal pancreas growth in vivo through treatments of the dams during their entire pregnancy. Pregnant rats were thus implanted subcutaneously with Alzet minipumps and received cerulein (0.25 μg kg^–1 h^–1), gastrin-releasing peptide (GRP; 0.18 μg kg^–1 h^–1), GRP antagonist (12 μg kg^–1 h^–1), pentagastrin (2.38 μg kg^–1 h^–1), L-365,260, a cholecystokinin B (CCK_B) receptor antagonist (120 μg kg^–1 h^–1), and hydrocortisone (417 or 833 μg kg^–1 h^–1). After sacrifice at the end of pregnancy, the pancreata of the dams and those of their fetuses were excised for weight, protein, RNA, DNA, and digestive enzyme determinations. In the fetus, pancreas growth defined as hyperplasia was observed only in response to hydrocortisone, while aplasia occurred in response to cerulein. Gastrin and the GRP antagonist were the most effective hypertrophic agents, and the effect of the CCK_B receptor antagonist was atrophic. In conclusion, hydrocortisone caused proliferation of the fetal rat pancreas, whereas gastrin induced its differentiation and maturation probably through CCK_B receptor occupation.

Gastrin, cholecystokinin and gastrointestinal tract functions in mammals

“…It remains to be seen if these gastrin effects are confined to rodents' pancreas. However, after birth, gastrin mRNA expression and the hormone content disappeared in the rat pancreas (Morisset et al 1999) and the CCK 2 receptors remained on the endocrine Δ cells (Morisset et al 2003); so it was not surprising to observe that postnatally, gastrin lost its trophic effect on the pancreatic gland as documented by many investigators (Chen et al 1996). Recently, evidence was presented for heterodimerisation of type 1 and 2 CCK receptors and that this complex can, once formed in transfected cells, become a powerful unit in promoting cell growth (Cheng et al 2003).…”

“…The estimation that fetal pancreas contains between 2·2 and 4 ng of gastrin (Brand & Fuller, 1988) and a majority of CCK 2 receptors (Morisset et al 2000 b ) lets us believe that this CCK 2 receptor subtype could be involved in fetal pancreas development. From studies performed with a CCK 2 receptor antagonist (Morisset et al 1999) and gastrin immunoneutralisation (Feurle et al 1995), both infused subcutaneously in the back of the dams for 28 d, showed that gastrin was involved in fetal pancreatic organogenesis. It remains to be seen if these gastrin effects are confined to rodents' pancreas.…”

Gastrin Stimulates β-Cell Neogenesis and Increases Islet Mass From Transdifferentiated but Not From Normal Exocrine Pancreas Tissue

“…This may represent a recapitulation of embryonic development, because it is known that gastrin and its receptor are expressed in the fetal pancreas (8 -11), and a role of gastrin in pancreatic development has been postulated (10,35).…”

The early story of growth hormone-releasing factor in rats, swine, and cattle

“…A total in vivo technique was also used whereby the hormonal control for rat fetal pancreas development was studied with different hormonal treatments given to the pregnant rats during their whole pregnancy (Morisset et al, 1999). The normal development of the pancreas has also been studied during gestation and lactation in swine (Charbonneau et al, 1982).…”