Anterior pituitary gland synthesises dopamine from <scp>l</scp>‐3,4‐dihydroxyphenylalanine (<scp>l</scp>‐dopa)

Orrillo, Santiago Jordi; Dios, Nataly de; Asad, Antonela Sofía; Fino, Fernanda De; Imsen, Mercedes; Romero, A. A.; Zárate, Sandra; Ferraris, Jimena; Pisera, Daniel

doi:10.1111/jne.12885

Cited by 5 publications

(4 citation statements)

References 71 publications

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“…The genetic algorithm employed in SOM AI PRO identified that SOM3355 had VMAT2 inhibitory activity, which was confirmed in vitro, with an IC50 in the nanomolar range similar to TBZ. The increase in plasma prolactin levels observed after treatment with SOM3355 is consistent with that seen with other VMAT2 inhibitors, 39 and probably reflects a reduction in dopaminergic tone in the hypothalamus and/or pituitary gland 40,41 …”

Section: Discussionsupporting

confidence: 76%

“…The increase in plasma prolactin levels observed after treatment with SOM3355 is consistent with that seen with other VMAT2 inhibitors, 39 and probably reflects a reduction in dopaminergic tone in the hypothalamus and/or pituitary gland. 40,41 Overall, the treatment in this trial with SOM3355 was safe and well-tolerated. The most frequent AEs were hypotension and bradycardia, which are consistent with the β 1 -adrenocepter blocking effect of bevantolol, but did not result in the discontinuation of the treatment; insomnia, which can be explained by the known effects of the drug, or because patients with HD are at increased risk of insomnia 37 (single fall rates between 21 and 75% and recurrent falls from 58 to 60% during early to mid-stage HD), with the consequent injuries and impact on their quality of life.…”

Section: Discussionmentioning

confidence: 79%

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A proof‐of‐concept study with SOM3355 (bevantolol hydrochloride) for reducing chorea in Huntington's disease

Gamez

Calopa

Muñoz

et al. 2022

Brit J Clinical Pharma

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The study's aim is to investigate the efficacy and safety of SOM3355 (bevantolol hydrochloride), a β 1 -adrenoreceptor antagonist with recently identified vesicular monoamine transporter type 2 inhibitory properties, as a repositioned treatment to reduce chorea in Huntington's disease (HD).Methods: A randomized, placebo-controlled proof-of-concept study was performed in 32 HD patients allocated to 2 arms of 4 sequential 6-week periods each. Patients received placebo and SOM3355 at 100 and 200 mg twice daily in a crossover design.The primary endpoint was improvement by at least 2 points in the total maximal chorea score in any active drug period compared with the placebo period.Results: The primary endpoint was met in 57.1% of the patients. Improvements ≥3, ≥4, ≥5 and ≥6 points vs. placebo treatment were observed in 28.6, 25.0, 17.9 and 10.7% of the patients, respectively. A mixed-model analysis found a significant improvement in the total maximal chorea score of À1.14 (95% confidence interval, À2.11 to À0.16; P = .0224) with 200 mg twice daily SOM3355 treatment compared with placebo treatment. These results were paralleled by Clinical and Patient Global Impression of Change ratings (secondary endpoints). An elevation in plasma prolactin levels by 1.7-1.9-fold was recorded (P < .005), probably reflecting the effect on the dopamine pathway, consistent with vesicular monoamine transporter type 2 inhibition. The most frequent adverse events during SOM3355 administration were mild to moderate. Conclusion:Within the limits of this study, the results suggest that SOM3355 reduces chorea in patients with HD and is well-tolerated. Larger studies are necessary to confirm its therapeutic utility as an antichoreic drug.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 79%

A proof‐of‐concept study with SOM3355 (bevantolol hydrochloride) for reducing chorea in Huntington's disease

Gamez

Calopa

Muñoz

et al. 2022

Brit J Clinical Pharma

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“…However, a recent study demonstrated that cells of the anterior pituitary gland can synthesise dopamine from L-DOPA by the local action of AADC. Moreover, locally produced dopamine was able to regulate PRL secretion [179]. We propose that our finding that Ddc is expressed in the adult pituitary gland and upregulated in pregnancy suggests an additional mechanism by which maternal PRL secretion is suppressed in gestation, and thus, merits further investigation.…”

Section: Imprinted Genes In the Pregnant Pituitary Glandmentioning

confidence: 71%

Dynamic Expression of Imprinted Genes in the Developing and Postnatal Pituitary Gland

Scagliotti

Esse

Willis

et al. 2021

Genes

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In mammals, imprinted genes regulate many critical endocrine processes such as growth, the onset of puberty and maternal reproductive behaviour. Human imprinting disorders (IDs) are caused by genetic and epigenetic mechanisms that alter the expression dosage of imprinted genes. Due to improvements in diagnosis, increasing numbers of patients with IDs are now identified and monitored across their lifetimes. Seminal work has revealed that IDs have a strong endocrine component, yet the contribution of imprinted gene products in the development and function of the hypothalamo-pituitary axis are not well defined. Postnatal endocrine processes are dependent upon the production of hormones from the pituitary gland. While the actions of a few imprinted genes in pituitary development and function have been described, to date there has been no attempt to link the expression of these genes as a class to the formation and function of this essential organ. This is important because IDs show considerable overlap, and imprinted genes are known to define a transcriptional network related to organ growth. This knowledge deficit is partly due to technical difficulties in obtaining useful transcriptomic data from the pituitary gland, namely, its small size during development and cellular complexity in maturity. Here we utilise high-sensitivity RNA sequencing at the embryonic stages, and single-cell RNA sequencing data to describe the imprinted transcriptome of the pituitary gland. In concert, we provide a comprehensive literature review of the current knowledge of the role of imprinted genes in pituitary hormonal pathways and how these relate to IDs. We present new data that implicate imprinted gene networks in the development of the gland and in the stem cell compartment. Furthermore, we suggest novel roles for individual imprinted genes in the aetiology of IDs. Finally, we describe the dynamic regulation of imprinted genes in the pituitary gland of the pregnant mother, with implications for the regulation of maternal metabolic adaptations to pregnancy.

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“…The mainly enriched pathway of Tyrosine metabolism involved in elevated levels of L-Dopa, HVA and Dopaquinone in AF patients with HF. In particular, HVA and Dopaquinone can be biosynthesized from L-Dopa, which was the precursor of dopamine [ 33 ]. As an endogenous catecholamine, dopamine worked as an autocrine and paracrine factor in the nonneuronal systems [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Integration of proteomic and metabolomic characterization in atrial fibrillation-induced heart failure

et al. 2022

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Background The exact mechanism of atrial fibrillation (AF)-induced heart failure (HF) remains unclear. Proteomics and metabolomics were integrated to in this study, as to describe AF patients’ dysregulated proteins and metabolites, comparing patients without HF to patients with HF. Methods Plasma samples of 20 AF patients without HF and another 20 with HF were analyzed by multi-omics platforms. Proteomics was performed with data independent acquisition-based liquid chromatography-tandem mass spectrometry (LC-MS/MS), as metabolomics was performed with LC-MS/MS platform. Proteomic and metabolomic results were analyzed separately and integrated using univariate statistical methods, multivariate statistical methods or machine learning model. Results We found 35 up-regulated and 15 down-regulated differentially expressed proteins (DEPs) in AF patients with HF compared to AF patients without HF. Moreover, 121 up-regulated and 14 down-regulated differentially expressed metabolites (DEMs) were discovered in HF patients compared to AF patients without HF. An integrated analysis of proteomics and metabolomics revealed several significantly enriched pathways, including Glycolysis or Gluconeogenesis, Tyrosine metabolism and Pentose phosphate pathway. A total of 10 DEPs and DEMs selected as potential biomarkers provided excellent predictive performance, with an AUC of 0.94. In addition, subgroup analysis of HF classification was performed based on metabolomics, which yielded 9 DEMs that can distinguish between AF and HF for HF classification. Conclusions This study provides novel insights to understanding the mechanisms of AF-induced HF progression and identifying novel biomarkers for prognosis of AF with HF by using metabolomics and proteomics analyses.

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Anterior pituitary gland synthesises dopamine from l‐3,4‐dihydroxyphenylalanine (l‐dopa)

Cited by 5 publications

References 71 publications

A proof‐of‐concept study with SOM3355 (bevantolol hydrochloride) for reducing chorea in Huntington's disease

A proof‐of‐concept study with SOM3355 (bevantolol hydrochloride) for reducing chorea in Huntington's disease

Dynamic Expression of Imprinted Genes in the Developing and Postnatal Pituitary Gland

Integration of proteomic and metabolomic characterization in atrial fibrillation-induced heart failure

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