Prolactin Modulates the Incidence of Diabetes in Male and Female Nod Mice

Abstract

The nonobese diabetic (NOD) mouse develops diabetes spontaneously due to autoimmune destruction of the pancreatic islets with a higher incidence in the female than the male. Prolactin (PRL), a hormone whose role has been previously focused on reproduction and lactation has been demonstrated to influence immune responses. In this study, we investigated the effect of hypoprolactinemia and hyperprolactinemia on the incidence of diabetes in male and female NOD mice. Our hypoprolactinemia model was induced from the time of weaning (21 days of age) to 112 days of age by daily injections of 200 μmlg of bromocriptine (CB-154). A hyperprolactinemic model was induced by a syngeneic anterior pituitary transplant (APT) to the kidney capsule at 35 days of age and maintained until 112 days of age. Additional experimental groups were also investigated. A group of males received pituitary transplants combined with daily subcutaneous injections of CB-154. A group of females treated with CB-154 was also given daily subcutaneous injections of 30 μmlg of oPRL. An ovariectomized (OVX-Control) group of females was also established to serve as a second control for the OVX-APT group. Bromocriptine administration did not significantly decrase plasma PRL levels compared to controls (CTRL) while APT animals had plasma PRL levels that were significantly higher (P < 0.01) than those of CTRL and CB-154 animals. These differences were observed in animals of both sexes. Bromocriptine treatment of APT groups significantly lowered plasma PRL levels from their respective controls. Plasma PRL from the OVX-Control group was markedly lower than the intact female control. The incidence of diabetes was significantly lower in female mice receiving CB-154 injections compared to the intact female CTRL group at 84, 98 and 112 days of age. CB-154 injections in males did not alter the incidence of diabetes significantly over the course of the experiment. The incidence of diabetes was significantly higher in APT males than CTRL, CB-154 and CB-154 + APT groups throughout the experiment. Prolactin administration to CB-154 treated female animals did not markedly alter the incidence of diabetes from that observed for CB-154 treatment alone, but at 42 days of age their incidence was higher than intact female CTRL (P > 0.02). OVX + APT did not significantly alter the diabetes incidence from that of intact females although a higher incidence was evident at an earlier age. When OVX + APT animals were compared to OVX animals, a sigificant increase was observed from 56 days until the end of the experiment (P > 0.0001). From these results we conclude that PRL can modulate the incidence of diabetes in NOD mice and hyperprolactinemia augments the autoimmune response leading to the development of diabetes.

Key Words:

• Prolactin
• Non-obese diabetic mouse
• Bromocriptine
• Anterior pituitary transplant
• Incidence of diabetes