Prolactin potentiates insulin-stimulated leptin expression and release from differentiated brown adipocytes

Abstract

The pituitary hormone prolactin (PRL) exerts pleiotropic effects, which are mediated by a membrane receptor (PRLR) present in numerous cell types including adipocytes. Brown adipose tissue (BAT) expresses uncoupling proteins (UCPs), involved in thermogenesis, but also secretes leptin, a key hormone involved in the control of body weight. To investigate PRL effects on BAT, we used the T37i brown adipose cell line, and demonstrated that PRLRs are expressed as a function of cell differentiation. Addition of PRL leads to activation of the JAK/STAT and MAP kinase signaling pathways, demonstrating that PRLRs are functional in these cells. Basal and catecholamine-induced UCP1 expression were not affected by PRL. However, PRL combined with insulin significantly increases leptin expression and release, indicating that PRL potentiates the stimulatory effect of insulin as revealed by the recruitment of insulin receptor substrates and the activation of phosphatidylinositol 3-kinase. To explore the in vivo physiological relevance of PRL action in BAT, we showed that leptin content was significantly increased in BAT of PRLR-null mice compared with wild-type mice, highlighting the involvement of PRL in the leptin secretion process. This study provides the first evidence for a functional link between PRL and energy balance via a cross-talk between insulin and PRL signaling pathways in brown adipocytes.

Serum prolactin concentrations determine whether they improve or impair β‐cell function and insulin sensitivity in diabetic rats

“…In mouse adipocytes, PRL alone has no effect on leptin release but it inhibits the insulin-induced production of leptin [33]. Conversely, when combined with insulin, PRL increases leptin release from brown adipocytes, which contradicts the higher concentration of leptin in brown adipose tissue in PRL receptor-deficient mice [34]. The present study showed that serum leptin levels did not differ with PRL treatment among diabetic groups.…”

Leptin levels in relation to marital status and neuroendocrine function in Iraqi females with polycystic ovary syndrome

“…The cross talk between prolactin and insulin signaling pathway in brown adipocytes demonstrated that prolactin potentiates insulin-stimulated secretion of leptin by brown adipose tissue (Viengchareun et al, 2004). In PCOS patients with hyperprolactinemia other causes must be investigated because hyperprolactinemia is not a clinical manifestation of PCOS (Filno et al, 2007).…”

Placental origins of adverse pregnancy outcomes: potential molecular targets: an Executive Workshop Summary of the Eunice Kennedy Shriver National Institute of Child Health and Human Development

“…169 resistin, 170 leptin 171 and adiponectin 172 are produced by fat during pregnancy in mice. Prl receptor signaling can regulate adipokine expression, 173,174,175 suggesting the possibility that while the mouse placenta is not the direct source of all metabolic hormones, unlike humans, it may still orchestrate the network. The best evidence in mice that placental hormones regulate fetal growth is that of the pleckstrin homology-like domain, family A member 2 gene which regulates the fetal growth by influencing the number of endocrine cells in the placenta.…”