Enhanced cell proliferation by hyperprolactinemia in both exocrine and endocrine pancreas in mice

Abstract

Effects of hyperprolactinemia induced by ectopic anterior pituitary grafting on the pancreas were studied in male SHN mice. After pituitary grafting, the weight of pancreas rapidly increased. A similar increase in pancreatic weight was observed during lactation, a condition associated with elevated prolactin levels. Results of DNA and protein assays revealed that the increase in pancreatic weight in both pituitary-grafted and lactating mice was mainly due to the increase in the cell number, because the total DNA content per pancreas was greater in these mice than the controls. An increase in fluid volume or hypertrophy of cells also contributes to the weight increase; in contrast, the DNA and protein contents per unit tissue weight decrease. The rate of DNA synthesis determined by 5-bromo-2'-deoxyuridine labeling was higher both in acinar cells and islet B cells in pituitary-grafted mice than in the controls. Thus, hyperprolactinemia stimulates cell proliferation in exocrine pancreas as well as endocrine islets. The effect of prolactin seems to be indirect on acinar cells, because only B cells showed prolactin immunoreactivity in the mouse pancreas. In addition, insulin might not be a mediator of the prolactin effect on acinar cells, because the serum insulin level in pituitary-grafted mice failed to show any change.

Lack of prolactin receptor signaling in mice results in lactotroph proliferation and prolactinomas by dopamine-dependent and -independent mechanisms

“…The inhibitory growth response of lactotrophs to PRL is quite different from the proliferative effect exhibited in nonpituitary cell types (14)(15)(16)(17)(18)(19)(21)(22)(23)(24)(25), in human prolactinoma cells (44), and in a transformed rat lactotroph cell line (20). It is, however, consistent with models of PRL effects on EGF and TGF-α signaling cascades.…”

“…Previously, both we (3) and another group (11) concluded from our original studies of Drd2 -/-mice that PRL most likely functioned as a mitogen for lactotrophs. In the majority of tissues where it has been evaluated, PRL is mitogenic (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25), with only a few tissues demonstrating an antiproliferative role (26)(27)(28)(29). However, we show here that in Prlr -/-mice, there are two factors contributing to the release of the lactotroph from its usual secretory and proliferative controls: a decrease in the normally inhibitory dopaminergic control and a second, direct effect at the level of the pituitary that is most consistent with an antiproliferative action of PRL on lactotrophs.…”

Effects of hyperprolactinemia on toxicological parameters and proliferation of islet cells in male rats

“…Therefore, they presumably were not involved in proliferation of islet cells under our experimental conditions. Glucocorticoids are known to alter pancreatic weight and function (Matsuda et al, 1994). However, dexamethasone (DEX) increased the amount of islet cell death (apoptosis) and counteracted the effect of PRL on islet function in an in vitro study (Weinhaus et al, 2000).…”

“…The role of toxicological evaluation is to protect humans from toxicity induced by drugs or other chemicals and unwanted side effects. It is necessary to assess and differentiate direct toxicological effects of compounds from their secondary effects.The anterior pituitary-grafted rat is well known as a useful model animal for research on hyperprolactinemia; many of which focused on hormonal changes, body weight or glucose metabolism (Matsuda et al, 1994;Reis et al, 1997;Adler, 1986) by means of this model although they had only patchy information. On the other hand, in females, physiological hyperprolactinemia is observed during pregnancy and the subsequent post partum lactation period.…”

Cortactin-Binding Protein 90 (CBP90) Expression in the Mouse Mammary Glands during Prolactin-Induced Lobuloalveolar Development

“…Transplantation of an anterior pituitary gland under the kidney capsule is widely used for stimulation of animals with PRL (Matsuda et al ., 1994). Expression of CBP90 mRNA was examined in the mammary glands and the cleared fat pads in pituitary-grafted wild-type mice by "virtual" northern hybridization (Fig.…”