Effects of Cholecystokinin Octapeptide and Hydrocortisone on the Development of Fetal Rat Pancreas

Abstract

Mechanisms and development of pancreas and pancreatic secretory function were studied in the rat. Injections of cholecystokinin octapeptide and hydrocortisone into pregnant rats altered pancreatic size, zymogen enzyme, and DNA content in the fetal newborn pancreas. These studies suggest that the developmental signals for pancreatic function may be related to endogenous release of cholecystokinin or hydrocortisone in the perinatal period.

Immunohistochemical Study of the Developing Endocrine Pancreas of the Opossum (<i>Didelphis virginiana</i>)

“…It has been suggested that some gastrointestinal peptides and classical endocrine glands may interact in the regulation of pancreatic growth and that of the gas trointestinal mucosa [Enochs and Johnson. 1977;Werlin andStefaniak. 1983: Johnson.…”

Hormonal Control of Rat Fetal Pancreas Development

“…Indeed, a 4-day treatment of hydrocortisone to females at the end of their pregnancy had no effect on fetal pancreas growth [11], while a 10-day [9] or a 21-day treatment (this study) caused significant fetal pancreas growth. The effect is also dose dependent, as shown in this study with hyperplasia observed only with the highest dose.…”

“…Such an effect, although previously observed by Werlin and Stefaniak [11], cannot be ascribed to occupation of the CCK A receptors, because their mRNA expression is minimal in the rat fetal pancreas [6]. If the fetal guinea pig pancreas expresses a majority of CCK B receptor mRNAs, as the fetal rat pancreas does, this would explain the lack of effect of the CCK A receptor antagonist MK329 given during the entire pregnancy to guinea pigs on fetal pancreatic weight and total protein, RNA, and DNA contents [12].…”

“…Pentagastrin (Peninsula, Belmont, Calif., USA) was infused at a dose of 2.38 Ìg kg -1 h -1 [20]. Hydrocortisone (a gift from Upjohn, Kalamazoo, Mich., USA) was infused at 417 or 833 Ìg kg -1 h -1 [11,21], and L-365,260, the CCK B receptor antagonist (a gift from Merck Sharp & Dohme, Westpoint, Pa., USA), was infused at 120 Ìg kg -1 h -1 , a dose 75% less than the 0.5 mg kg -1 h -1 of L-364,718 infused in the adult rat which inhibited pancreas growth induced by pancreatic juice diversion [22]. All hormones and the GRP antagonist were dissolved in saline, while L-365,260 was dissolved in a mixture of dimethyl sulfoxide (DMSO) and water (1:2.8 vol/vol).…”

“…Infusion of the CCK A receptor antagonist devazepide and an antigastrin/CCK monoclonal immunoglobulin G in the rat during the entire period of gestation led to decreases in total pancreatic protein and DNA contents of the fetus without any change in pancreas weight [10]. An earlier study presented opposite results, as a CCK-8 treatment to pregnant rats on days 16-19 of their pregnancy had no effect on pancreatic weight and protein content of their term fetuses, but showed significant decreases in the pancreatic total DNA content [11]. In guinea pigs, infusion of the CCK A receptor antagonist MK329 during the entire pregnancy had no effect on pancreatic growth parameters, suggesting that this CCK receptor type was not involved in fetal pancreas development [12].…”