The role of the prolactin/vasoinhibin axis in rheumatoid arthritis: an integrative overview

Clapp, Carmen; Adán, Norma; Ledesma-Colunga, María G.; Solís-Gutiérrez, Mariana; Triebel, Jakob; Escalera, Gonzálo Martínez de la

doi:10.1007/s00018-016-2187-0

Cited by 29 publications

(23 citation statements)

References 245 publications

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“…Studies on PRL levels in RA have provided inconsistent results with lower, higher, or equivocal values [139,147]. It has been shown that the risk and severity of RA are decreased in reproductive states characterized by hyperprolactinaemia (pregnancy and breastfeeding) [148]. However, others have demonstrated that severe disease is associated with longer period of breast-feeding and larger number of breastfed children [149].…”

Section: Rheumatoid Arthritismentioning

confidence: 99%

“…Various hypotheses have been proposed for the inconsistent findings. It has been postulated that lower PRL levels are immunostimulatory, whereas higher ones are immunosuppressive [148]. Others have suggested that extra-pituitary PRL is more important in the pathogenesis of RA than pituitary PRL; PRL-receptors have been demonstrated in synovial macrophages, and PRL mRNA expression in synovial tissue is positively correlated with clinical disease activity [147,151].…”

Section: Rheumatoid Arthritismentioning

confidence: 99%

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Hyperprolactinaemia

Samperi

Lithgow

Karavitaki

2019

JCM

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Hyperprolactinaemia is one of the most common problems in clinical endocrinology. It relates with various aetiologies (physiological, pharmacological, pathological), the clarification of which requires careful history taking and clinical assessment. Analytical issues (presence of macroprolactin or of the hook effect) need to be taken into account when interpreting the prolactin values. Medications and sellar/parasellar masses (prolactin secreting or acting through "stalk effect") are the most common causes of pathological hyperprolactinaemia. Hypogonadism and galactorrhoea are well-recognized manifestations of prolactin excess, although its implications on bone health, metabolism and immune system are also expanding. Treatment mainly aims at restoration and maintenance of normal gonadal function/fertility, and prevention of osteoporosis; further specific management strategies depend on the underlying cause. In this review, we provide an update on the diagnostic and management approaches for the patient with hyperprolactinaemia and on the current data looking at the impact of high prolactin on metabolism, cardiovascular and immune systems.

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Section: Rheumatoid Arthritismentioning

confidence: 99%

Section: Rheumatoid Arthritismentioning

confidence: 99%

Hyperprolactinaemia

Samperi

Lithgow

Karavitaki

2019

JCM

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“…Recent evidence suggests that estrogens can have both pro- and anti-inflammatory activities (16), and similar pro- and anti-inflammatory effects of PRL in RA have been recently reviewed (14, 15). For decades it has been acknowledged that in about 65% of the RA patients, disease activity diminishes during pregnancy.…”

Section: Endocrine Hormones In Ramentioning

confidence: 99%

Insight into the Endocrine System and the Immune System: A Review of the Inflammatory Role of Prolactin in Rheumatoid Arthritis and Psoriatic Arthritis

et al. 2017

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Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects females three times more frequently than males. A potential role for hormones, such as prolactin (PRL), may in part explain this phenomenon. The risk of developing RA is increased in women who are lactating after the first pregnancy, which might be related to breastfeeding and the release of PRL. Other studies found a protective effect of PRL on RA development. Some studies have reported that hyperprolactinemia is more common in RA and serum PRL levels are correlated with several disease parameters, although others could not confirm these findings. Overall the plasma PRL levels are on average not elevated in RA. Previously, a small number of open-label clinical trials using bromocriptine, which indirectly decreases PRL levels, were performed in RA patients and showed clinical benefit, although others found the opposite effect. Locally produced PRL at the site of inflammation may have a crucial role in RA as well, as it has been shown that PRL can be produced by synovial macrophages. Locally produced PRL has both pro-inflammatory and anti-inflammatory effects in arthritis. Psoriatic arthritis (PsA) is also an autoinflammatory disease, in which the prolactin receptor is also expressed in macrophages. The aim of this review is to provide an overview of the potential role of PRL signaling in inflammatory joint diseases (RA and PsA) and its potential as a therapeutic target.

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“…This list had previously comprised only the condition of prolactinoma and the inhibition or PRL-release for ablactation or secondary amenorrhea. Of note, there are more clinical entities in which studies reported that a dysregulation of PRL and of the PRL/vasoinhibin axis might play a role, for example, breast and prostate cancer ( 71 – 75 ), preeclampsia and eclampsia ( 67 , 76 , 77 ), pregnancy-induced hypertension ( 78 ), pulmonary artery hypertension ( 79 ), retinopathy of prematurity ( 28 ), and rheumatoid arthritis ( 80 ). These conditions require thorough clinical investigation, including determination of PRL and vasoinhibin levels, and, ideally, additional experimental validation.…”

Section: Perspectivesmentioning

confidence: 99%

From Bench to Bedside: Translating the Prolactin/Vasoinhibin Axis

et al. 2017

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The prolactin/vasoinhibin axis defines an endocrine system, in which prolactin (PRL) and vasoinhibins regulate blood vessel growth and function, the secretion of other hormones, inflammatory and immune processes, coagulation, and behavior. The core element of the PRL/vasoinhibin axis is the generation of vasoinhibins, which consists in the proteolytic cleavage of their precursor molecule PRL. Vasoinhibins can interact with multiple different partners to mediate their effects in various tissues and anatomical compartments, indicating their pleiotropic nature. Based on accumulating knowledge about the PRL/vasoinhibin axis, two clinical trials were initiated, in which vasoinhibin levels are the target of therapeutic interventions. One trial investigates the effect of levosulpiride, a selective dopamine D2-receptor antagonist, on retinal alterations in patients with diabetic macular edema and retinopathy. The rationale of this trial is that the levosulpiride-induced hyperprolactinemia resulting in increased retinal vasoinhibins could lead to beneficiary outcomes in terms of a vasoinhibin-mediated antagonization of diabetes-induced retinal alterations. Another trial investigated the effect of bromocriptine, a dopamine D2-receptor agonist, for the treatment of peripartum cardiomyopathy. The rationale of treatment with bromocriptine is the inhibition of vasoinhibin generation by substrate depletion to prevent detrimental effects on the myocardial microvascularization. The trial demonstrated that bromocriptine treatment was associated with a high rate of left ventricular recovery and low morbidity and mortality. Therapeutic interventions into the PRL/vasoinhibin axis bear the risk of side effects in the areas of blood coagulation, blood pressure, and alterations of the mental state.

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The role of the prolactin/vasoinhibin axis in rheumatoid arthritis: an integrative overview

Cited by 29 publications

References 245 publications

Hyperprolactinaemia

Hyperprolactinaemia

Insight into the Endocrine System and the Immune System: A Review of the Inflammatory Role of Prolactin in Rheumatoid Arthritis and Psoriatic Arthritis

From Bench to Bedside: Translating the Prolactin/Vasoinhibin Axis

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