Metabolic syndrome associated with hyperprolactinemia: A new indication for dopamine agonist treatment?

Abstract

In this issue of Endocrine, Inancli and co-authors presentthe manuscript ‘‘Effect of cabergoline on insulin sensitivity,inflammation, and carotid intima media thickness inpatients with prolactinoma’’ [1]. They found that cabergo-line treatment was associated with significant improve-ments in body mass index; total, HDL, and LDL-cholesterollevels and insulin sensitivity, also with a decrease in pro-inflammatory markers and carotid intima media thickness.Only the decrease in total and LDL-cholesterol showed apositive correlation with PRL levels. They concluded thatpatients with prolactinoma may have a higher vascular riskand cabergoline treatment may be associated with betterendothelial function [1].The human prolactin (PRL) is mainly produced bypituitary lactotrophs under inhibitory control of hypotha-lamic dopamine. The main and best-known effect of thePRL is the stimulation of lactogenesis and the maintenanceof lactation (galactopoiesis). However, PRL is also syn-thetized in extra-pituitary sites (decidua, myometrium,lymphocytes, and adipocytes) exerting several functions asa ‘‘metabolic hormone’’ [2–4].The human PRL gene is located on chromosome 6, hassix exons and two transcriptional start sites for extra-pitu-itary and for pituitary PRL. The regulation of PRL genetranscription is also different, requiring interaction withPit-1 at pituitary level and with several not well-knowntissue-specific factors for each extra-pituitary site [4].However, the final protein, PRL, is the same at pituitaryand extra-pituitary sites. In contrast with the pituitary PRLsecretion, the regulation of PRL extra-pituitary secretion islargely unknown.The PRL receptor is widely expressed in human bodyand mediates PRL actions by activation of JAK2/STAT5,PI3K, and MAPK pathways [4]. Regardless of its origin,PRL is able to interact with PRL receptors of any bodylocation. However, the mechanisms regulating the expres-sion of PRL receptor (and its different isoforms) in eachextra-pituitary tissue are basically unknown. This complexsystem could explain the absence of relationship betweencirculating PRL levels and some of the metabolic effects(mainly autocrine or paracrine) of PRL.The metabolic (extra-mammary gland) effects of PRLhave been reviewed elsewhere [2–5] and can be summa-rized as follows: (a) during the perinatal and postnatalperiods pancreatic islet cells development and insulinsecretion are promoted; (b) food intake and weight gainare also promoted; (c) adipogenesis inhibiting lipolysis isstimulated, which alters the release of adipokines includingleptin, adiponectin, and inter-leukin 6, promoting insulinresistance, hyper insulinemia, endothelial dysfunction, andmetabolic syndrome; (d) citrate production in prostaticcells is stimulated and finally, (e) the negative effects ofglucocorticoids on the immune system during stress arecounteracted [6].The appropriate treatment with dopamine agonists inpatients diagnosed with hyperprolactinemia have beenassociated with variable reduction in weight [1, 7], body fat[8], cardiovascular risk markers, cholesterol [1, 9–11], andendothelial dysfunction [1]. In patients with chronic kidney