Molecular Pathways in Prolactinomas: Translational and Therapeutic Implications

Biagetti, Betina; Simó, Rafael

doi:10.3390/ijms222011247

Cited by 6 publications

(7 citation statements)

References 92 publications

(128 reference statements)

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“…Prolactin, dopamine and other factors control lactotroph homeostasis ( 7 , 19 , 48 , 52 , 65 ). For patients where dopamine agonists are inefficient, it is worth consideringwhether the pathogenesis of those tumors is the same as in those responsive to dopamine.…”

Section: Discussionmentioning

confidence: 99%

“…If such factors can be identified, the exploration, for example, of PRLR or PRLR-associated pathways, not only in terms of mutations but also in gene expression regulation or modulatory molecules using high throughput technologies in patients, could help in designing a specific personalized therapy ( 63 , 65 , 67 , 68 ),…”

Section: Discussionmentioning

confidence: 99%

“…All of them are related to paracrine/autocrine PRL effects in the pituitary; for all, there are already described pharmacological modulators and thus are relevant pharmacological targets for potential aggressive prolactinomas. Nevertheless, no clinical trial currently assesses these therapeutic options ( 65 ).…”

Section: Prolactin Prolactin Receptor and Signaling Pathways Associat...mentioning

confidence: 99%

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Is prolactin receptor signaling a target in dopamine-resistant prolactinomas?

Ferraris

2023

Front. Endocrinol.

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The hypothalamic neuroendocrine catecholamine dopamine regulates the lactotroph function, including prolactin (PRL) secretion, proliferation, and apoptosis. The treatment of PRL-secreting tumors, formerly known as prolactinomas, has relied mainly on this physiological characteristic, making dopamine agonists the first therapeutic alternative. Nevertheless, the group of patients that do not respond to this treatment has few therapeutical options. Prolactin is another physiological regulator of lactotroph function, acting as an autocrine/paracrine factor that controls PRL secretion and cellular turnover, inducing apoptosis and decreasing proliferation. Furthermore, the signaling pathways related to these effects, mainly JAK/STAT and PI3K/Akt, and MAPK, have been extensively studied in prolactinomas and other tumors as therapeutic targets. In the present work, the relationship between PRL pathophysiology and prolactinoma development is explored, aiming to comprehend the value of PRL and PRLR-associated pathways as exploratory fields alternative to dopamine-related approaches, which are worth physiological characteristics that might be impaired and can be potentially restored or upregulated to provide more options to the patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Prolactin Prolactin Receptor and Signaling Pathways Associat...mentioning

confidence: 99%

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Is prolactin receptor signaling a target in dopamine-resistant prolactinomas?

Ferraris

2023

Front. Endocrinol.

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“…The five different dopamine receptors can be dived into two categories depending on the action of the G protein. 53,54 When dopamine binds to the D2 receptor, it leads to the expression of certain genes and the reduction of prolactin exocytosis. [55][56][57][58][59] As with these findings, in previous studies, subacute exposure to styrene led to dopamine depletion in rabbits.…”

Section: Discussionmentioning

confidence: 99%

Relationship between styrene exposure and prolactin secretion in human and animal studies: A systematic review

et al. 2022

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Styrene is widely used in industrial applications. Inhalation exposure occurs in the industry. Some studies indicated that serum prolactin concentrations increased after exposure to styrene, while other studies found no change. In this systematic review, the search was done with the keywords styrene and prolactin in the PubMed, Science Direct, Web of Science and Scopus databases, regardless of the publication period. 118 studies were obtained and only seven articles were finally selected according to exclusion and inclusion criteria. The effect of styrene on prolactin secretion was selected in both human and animal studies. The increased response was seen in inhalation exposures. Subcutaneous exposure has no significant effect on prolactin levels. The observed responses were both dose-dependent and gender-dependent. Changes in serum prolactin were more frequent in women compared to exposed men. Dopamine depletion was not observed in all studies, so more tests on laboratory animals are necessary to clarify the possible mechanism.

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“…32,33 In healthy individuals, binding of dopamine to D2 receptors inhibits the release of secretory granules containing prolactin within seconds, but it takes persistent dopamine action and days before inhibition of lactotroph proliferation. 34 The notoriously short half-life of L-Dopa, even if administered together with a DCI, is responsible for the fluctuation of symptoms in patients with Parkinson's disease and inherited neurotransmitter disorders treated with L-Dopa/DCI, and may necessitate 3-6 daily doses. 15 A single case study from 1998 clearly demonstrated that even with 6-time dosing of L-Dopa during daytime, prolactin concentrations remain high during the night, but the peaks are markedly ameliorated just by switching to 3-time dosing of a slow-release formulation.…”

Section: Treatment and Clinical Follow-upmentioning

confidence: 99%

Levodopa‐refractory hyperprolactinemia and pituitary findings in inherited disorders of biogenic amine metabolism

Yıldız

Hübschmann

Karaosmanoglu

et al. 2023

J of Inher Metab Disea

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Elevated serum prolactin concentrations occur in inherited disorders of biogenic amine metabolism because dopamine deficiency leads to insufficient inhibition of prolactin secretion. This work from the International Working Group on Neurotransmitter Related Disorders (iNTD) presents the results of the first standardized study on levodopa‐refractory hyperprolactinemia (LRHP; >1000 mU/L) and pituitary magnetic resonance imaging (MRI) abnormalities in patients with inherited disorders of biogenic amine metabolism. Twenty‐six individuals had LRHP or abnormal pituitary findings on MRI. Tetrahydrobiopterin deficiencies were the most common diagnoses (n = 22). The median age at diagnosis of LRHP was 16 years (range: 2.5–30, 1st–3rd quartiles: 12.25–17 years). Twelve individuals (nine females) had symptoms attributed to hyperprolactinemia: menstruation‐related abnormalities (n = 7), pubertal delay or arrest (n = 5), galactorrhea (n = 3), and decreased sexual functions (n = 2). MRI of the pituitary gland was obtained in 21 individuals; six had heterogeneity/hyperplasia of the gland, five had adenoma, and 10 had normal findings. Eleven individuals were treated with the dopamine agonist cabergoline, ameliorating the hyperprolactinemia‐related symptoms in all those assessed. Routine monitoring of these symptoms together with prolactin concentrations, especially after the first decade of life, should be taken into consideration during follow‐up evaluations. The potential of slow‐release levodopa formulations and low‐dose dopamine agonists as part of first‐line therapy in the prevention and treatment of hyperprolactinemia should be investigated further in animal studies and human trials. This work adds hyperprolactinemia‐related findings to the current knowledge of the phenotypic spectrum of inherited disorders of biogenic amine metabolism.

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Molecular Pathways in Prolactinomas: Translational and Therapeutic Implications

Cited by 6 publications

References 92 publications

Is prolactin receptor signaling a target in dopamine-resistant prolactinomas?

Is prolactin receptor signaling a target in dopamine-resistant prolactinomas?

Relationship between styrene exposure and prolactin secretion in human and animal studies: A systematic review

Levodopa‐refractory hyperprolactinemia and pituitary findings in inherited disorders of biogenic amine metabolism

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