摘要：

Prolactin (PRL) in humans is produced by both the pituitary and extrapituitary sites, where it acts as a cytokine. We previously found that human adipose tissue from several depots produces and secretes PRL. PRL has multiple functions in adipose tissue, including regulation of adipokine release and inhibition of lipolysis, but the factors that control its production are unknown. Although dopamine (DA) is the primary inhibitor of pituitary PRL, it has not been previously considered a suppressor of extrapituitary PRL. DA binds to five receptors (DAR) classified as those that stimulate (D1R and D5R) or inhibit (D2R, D3R and D4R) adenylate cyclase and cAMP accumulation. However, expression of DAR in adipocytes has not been reported. Most DA in serum is in the form of dopamine sulfate (DA-S), which can be de-conjugated back into DA by arylsulfatase A (ARSA).;Our objectives were to: (a) evaluate PRL release over time from visceral (vis) and subcutaneous (sc) adipose tissue and mature adipocytes from both non-obese and obese patients, (b) compare the regulation of PRL production by cAMP activators, insulin and selected cytokines from primary adipocytes and LS14 cells before and after differentiation, (c) examine whether human adipose tissue and adipocytes express functional DAR, (d) identify the source of DA for adipose tissue by analyzing ARSA expression and activity as well as the effect of DA-S in adipocytes, (e) determine whether DA inhibits PRL production, and (f) examine whether DA regulates other adipocyte functions, including lipolysis and leptin release.;We found a delayed rise in PRL release from both vis and sc adipose tissue and mature adipocytes cultured in vitro, suggesting removal from an endogenous inhibitor. PRL release from sc adipose tissue was inversely related to BMI. While insulin inhibited PRL gene expression and release in differentiated adipocytes, it stimulated PRL production in undifferentiated cells. Activators of cAMP induced PRL secretion in both cells types. DAR was expressed at both the mRNA and protein levels in adipose tissue and adipocytes. The ratio of DAR expression varied throughout differentiation of primary preadipocytes and two human adipocyte cell-lines, LS14 and SW872. Adipocytes expressed ARSA, whose activity was elevated after differentiation. Acting via the D2R, DA suppressed intracellular cAMP accumulation and PRL gene expression and release from adipocytes. Utilizing D1-like receptors, DA increased leptin release and lipolysis. DA-S had a similar effect as DA on PRL and leptin release as well as lipolysis, indicating that it can be converted to bioactive DA by ARSA.;In conclusion, this is the first demonstration of functional DAR and ARSA in human adipocytes. These results suggest that adipocyte DAR are involved in normal metabolic homeostasis and the weight gain associated with antipsychotic medications that antagonize the D2R. PRL appears to be an important adipokine whose release is controlled by insulin and DA and is associated with body weight regulation.

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