Trends in Endocrinology & Metabolism
Focus on prolactin as a metabolic hormone
Introduction
The metabolic status of an organism is finely regulated by nutritional status, energy expenditure and hormonal signals. Organs such as the pancreas, liver and adipose tissue respond to these cues and regulate metabolic homeostasis. Prolactin (PRL) is a multifunctional pituitary hormone, and PRL receptors (PRLRs) are expressed in nearly all organs. In humans, PRL is also produced at extrapituitary sites, so it is classified as a circulating hormone and an autocrine or paracrine factor. PRL has more functions than all other pituitary hormones combined. These actions can be categorized broadly as reproductive, metabolic, osmoregulatory and immunoregulatory. Since the publication of several comprehensive reviews on PRL 1, 2, 3, new information has emerged that warrants an update on its metabolic functions. In this review, we first describe the global effects of PRL on body composition, followed by its metabolic actions in four target tissues: breast, adipose, pancreas and prostate (Figure 1).
Section snippets
Global actions of PRL on body weight and adiposity
Studies on rats provide the most consistent data on the effects of PRL on body composition. Chronic elevation of PRL, induced by dopamine antagonists, daily injections of PRL and ectopic pituitaries, are associated with increased food intake and body weight, but gain in adipose-tissue mass is not well documented 4, 5, 6, 7. Suppression of PRL release by bromocriptine results in the opposite outcome, and is most effective in lactating rats and least effective in males 5, 8. Injections of PRL
Regulation of mammary-gland metabolism by PRL
PRL has a commanding role in cellular growth, differentiation, secretion and involution of the mammary gland. However, assessment of the direct metabolic actions of PRL is hampered by several limitations. First, initiation (lactogenesis) and maintenance (galactopoiesis) of lactation are complex processes that require the sequential, orchestrated actions of many hormones. PRL has a more dominant role during lactation in rabbits, rodents and humans, and a lesser role in ruminants. Second,
Metabolic and endocrine actions of PRL on adipose tissue
Adipose tissue is an active organ that plays a pivotal role in metabolic, physiological and endocrine homeostasis. Based on the notion that PRLRs are not present in adipose tissue, PRL was considered previously to be an indirect regulator of adipose tissue [23]. However, with new evidence to the contrary, this concept should be revisited. Indeed, PRLRs are present in brown and white adipose tissue from several species 11, 32, 33, 34, 35. At the protein level, the long-PRLR isoform and several
PRL as an autocrine or paracrine factor in human adipose tissue
PRL production in human adipose tissue was discovered serendipitously during studies of PRL release by human breast explants. Intended as a negative control, breast adipose tissue was found to release 10–15-times more PRL than glandular tissue [29]. PRL release from glandular tissue is inhibited by progesterone, but neither estrogen nor progesterone alters the release of PRL from adipose tissue, which indicates that regulation of PRL release is different in the two adjacent compartments. These
Effects of PRL on growth of pancreatic islets and insulin secretion
Lactogenic hormones are important regulators of the growth of pancreatic islets and their function during the perinatal period. Because a unique receptor for placental lactogens has not been identified, the general consensus is that the PRLR serves both PRL and placental lactogens. In early fetal life, the PRLR is expressed primarily in islet acinar cells and ducts, and becomes more prominent in insulin-producing and glucagon-producing cells during the perinatal and postnatal periods [53].
PRL stimulates citrate production in prostatic cells
Increased biosynthesis of citrate in the prostate gland in response to PRL is a fine example of its coordinated effects on key metabolic enzymes. As reviewed by Costello and Franklin [64], the prostate secretes unusually high levels of citrate, which has important functions in the normal gland, whereas its production is decreased markedly in prostate cancer. Unlike other cells, in which citrate is an intermediate metabolite, it is the end-product in prostate cells. As depicted in Figure 3, two
Conclusions and future directions
The metabolic actions of PRL are not confined to the lactating mammary gland. Globally, excess PRL correlates with changes in food intake and body weight in some species, although it has marginal effects on fat deposition. Emerging data indicate that PRL has a role in whole-body insulin sensitivity by stimulating insulin release and regulating adipokine release. The recent finding of lower release of PRL from human subcutaneous adipose tissue from obese compared with lean individuals indicates
Acknowledgements
This work was supported by the National Institutes of Health grants ES012212 and CA096613 (N.B.-J.), and training grant DK59803 (E.R.H. and T.D.B.).
References (67)
Comparative effects of the antipsychotics sulpiride and risperidone in female rats on energy balance, body composition, fat morphology and macronutrient selection
Prog. Neuropsychopharmacol. Biol. Psychiatry
(2004)Effects of hypersecretion of growth hormone and prolactin on plasma levels of glucagon and insulin in GH3-cell-tumor-bearing rats, and the influence of bromocriptine treatment
Life Sci.
(1986)Hyperprolactinemia stimulates food intake in the female rat
Brain Res. Bull.
(1986)- et al.
Neuroanatomical specificity of prolactin-induced hyperphagia in virgin female rats
Brain Res.
(2000) Chronic effect of hyperprolactinemia on blood glucose and lipid levels in mice
Life Sci.
(1996)Transcription factor regulation in mammary epithelial cells
Domest. Anim. Endocrinol.
(2002)Prolactin and the regulation of adipose-tissue metabolism during lactation in rats
Mol. Cell. Endocrinol.
(1981)Increased resistin expression in the adipose tissue of male prolactin transgenic mice and in male mice with elevated androgen levels
FEBS Lett.
(2001)STAT 5 activators can replace the requirement of FBS in the adipogenesis of 3T3-L1 cells
Biochem. Biophys. Res. Commun.
(2004)Development of lipoprotein lipase activity and accumulation of triacylglycerol in differentiating 3T3-L1 adipocytes. Effects of prostaglandin F2alpha, 1-methyl-3-isobutylxanthine, prolactin, and insulin
J. Biol. Chem.
(1979)
The adipocyte in insulin resistance: key molecules and the impact of the thiazolidinediones
Trends Endocrinol. Metab.
Prolactin and growth hormone regulate adiponectin secretion and receptor expression in adipose tissue
Biochem. Biophys. Res. Commun.
Prolactin-modulated gene expression profiles in pancreatic islets from adult female rats
Mol. Cell. Endocrinol.
Cyclic adenosine 3′,5′-monosphosphate mediate prolactin regulation of mitochondrial aconitase in human prostate carcinoma cells
Mol. Cell. Endocrinol.
Extrapituitary prolactin: distribution, regulation, functions and clinical aspects
Endocr. Rev.
Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice
Endocr. Rev.
Prolactin: structure, function, and regulation of secretion
Physiol. Rev.
Stimulation of food intake and weight gain in mature female rats by bovine prolactin and bovine growth hormone
Am. J. Physiol.
Prolactin inhibition in lactating rats changes leptin transfer through the milk
Horm. Metab. Res.
Prolactin (PRL) receptor gene expression in mouse adipose tissue: increases during lactation and in PRL-transgenic mice
Endocrinology
Body weight and fat deposition in prolactin receptor-deficient mice
Endocrinology
Roles of the lactogens and somatogens in perinatal and postnatal metabolism and growth: studies of a novel mouse model combining lactogen resistance and growth hormone deficiency
Endocrinology
Lack of prolactin receptor signaling in mice results in lactotroph proliferation and prolactinomas by dopamine-dependent and -independent mechanisms
J. Clin. Invest.
Body weight gain after administration of antipsychotic drugs: correlation with leptin, insulin and reproductive hormones
Pharmacopsychiatry
Dopaminergic tone and obesity: an insight from prolactinomas treated with bromocriptine
Eur. J. Endocrinol.
Increased body weight associated with prolactin secreting pituitary adenomas: weight loss with normalization of prolactin levels
Clin. Endocrinol. (Oxf.)
Interactions of prolactin and growth hormone (GH) in the regulation of mammary gland function and epithelial cell survival
J. Mammary Gland Biol. Neoplasia
Hormonal regulation of mammary differentiation and milk secretion
J. Mammary Gland Biol. Neoplasia
The comparative biology of whey proteins
J. Mammary Gland Biol. Neoplasia
Effect of prolactin on 2-deoxyglucose uptake in mouse mammary gland explants
Am. J. Physiol.
Effects of growth hormone and prolactin on adipose tissue development and function
Pituitary
Prolactin's effects on lipoprotein lipase (LPL) activity and on LPL mRNA levels in cultured mouse mammary gland explants
Proc. Soc. Exp. Biol. Med.
Control of rat mammary-gland pyruvate dehydrogenase by insulin and prolactin
Biochem. J.
Cited by (265)
Nonalcoholic Fatty Liver Disease, Bone and Muscle Quality in Prolactinoma: A Pilot Study
2024, Journal of Clinical DensitometryMetabolic association of serum prolactin in polycystic ovary syndrome: A retrospective analysis of 840 patients in Bangladesh
2024, Endocrine and Metabolic SciencePlant growth promoting rhizobacteria (PGPR): an overview for sustainable agriculture and development
2023, Rhizobiome: Ecology, Management and ApplicationCharacterization of long noncoding RNA in nonlactating goat mammary glands reveals their regulatory role in mammary cell involution and remodeling
2022, International Journal of Biological Macromolecules