The Prolactin-Deficient Mouse Has an Unaltered Metabolic Phenotype

Abstract

Prolactin (PRL), best recognized for its lactogenic activity, is also involved in the regulation of metabolic homeostasis in both mammalian and nonmammalian species. Although several mouse models have been used to study the metabolic functions of PRL, a clear-cut consensus has not emerged given the limited and often conflicting data. To clarify the role of PRL in metabolic homeostasis in males and nonlactating females, we used the PRL-deficient mouse. Our objectives were to compare: 1) weight gain, 2) body composition, 3) serum lipid profile, 4) circulating leptin and adiponectin levels, and 5) glucose tolerance in PRL knockout, heterozygous, and wild-type mice maintained on standard chow, high-fat, or low-fat diets. In addition, we compared the lipolytic actions of PRL using adipose tissue explants from mice, rats, and humans. We are reporting that PRL deficiency does not affect the rate of weight gain, body composition, serum lipids, or adiponectin levels in either sex on any diet. Glucose tolerance was slightly impaired in very young PRL knockout male pups but not in adults or in females at any age. Leptin was elevated in male, but not female, PRL knockout mice maintained on a low-fat diet. PRL did not affect lipolysis in adipose tissue explants from mice but significantly inhibited glycerol release from both rat and human adipose explants in a dose-dependent manner. We conclude that PRL deficiency has negligible gross metabolic effects in mice.

Prolactin upregulates its receptors and inhibits lipolysis and leptin release in male rat adipose tissue

“…Such discrepancies may be due to different incubation conditions or species variability. Indeed, we reported that PRL at low concentrations had anti-lipolytic actions on both human and rat adipose explants, but did not affect lipolysis in mouse adipose explants [25].…”

“…Data on PRL and adiponectin are also inconsistent. Whereas serum adiponectin levels are unchanged in PRLR- [6] or PRL-knockout mice [25], PRL at very high doses inhibits adiponectin production in cultured human adipose tissue and in mice in vivo [6,31]. Lower circulating adiponectin levels were reported in lactating women, with inhibition of adiponectin production in cultured human adipocytes by PRL [32].…”

“…For example, serum leptin levels are lower [5] or unchanged [30] in PRLR-deficient mice, and are elevated in PRLoverexpressing mice [4]. An inhibitory effect of PRL, however, is suggested by the higher serum leptin in male PRL-knockout mice [25], and the inhibition of insulin-stimulated leptin release in mouse adipocytes [4]. Data on PRL and adiponectin are also inconsistent.…”

Fyn Regulates Adipogenesis by Promoting PIKE-A/STAT5a Interaction

“…Accumulating evidence also suggests that PRL is implicated in adipogenesis. Freemark et al reported that PRLR knockout mice have reduced fat deposition, but no such change in adipose mass was detected by a subsequent study (44,45). Given that in vivo adipogenesis is affected by numerous factors, including genetic background, hormone status, age, and the type of food intake, it is reasonable to find that the relationship between PRL and adiposity in intact animals is not conclusive.…”

Hormonal regulation of longevity in mammals

“…Prolactin-receptor mediated signaling is not likely involved in regulating insulin sensitivity in adult mice as both hypoprolactinemic Ames mice and hyperprolactinemic GHR/BP KO mice exhibit enhanced responses to insulin (reviewed in Bartke 2005). In agreement, a recent report utilizing prolactin deficient animals indicates that a lack of prolactin has negligible metabolic effects in mice (LaPensee et al, 2006).…”