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Aging Jun 2021Dopamine receptor, a polypeptide chain composed of 7 hydrophobic transmembrane regions, is a new and vital drug target, especially Dopamine receptor 2(D2). Targeting...
Dopamine receptor, a polypeptide chain composed of 7 hydrophobic transmembrane regions, is a new and vital drug target, especially Dopamine receptor 2(D2). Targeting dopamine receptors, Dopamine receptor agonists are a class of drugs similar in function and structure to dopamine and can directly act on dopamine receptors and activate it. Clinically, Dopamine receptor agonist drugs have achieved significant therapeutic effects on prolactinoma and Parkinson's Disease. In the study, we virtually screened a series of potential effective agonists of Dopamine receptor by computer techniques. Firstly, we used the Molecular Docking (LibDock) step to screen out some molecules that can dock well with the protein. Then, analysis of toxicity prediction and ADME (adsorption, distribution, metabolism and excretion) were carried out. More precise molecular docking (CDOCKER) and 3-Dimensional Quantitative Structure-Activity Relationship Modeling Study(3D-QSAR) pharmacophore generation were implemented to research and explore these compounds' binding mechanism with Dopamine receptor. Last but not least, to assess compound's binding stabilities, we carried out a molecular dynamic analysis. As the results show, two compounds (ZINC000008860530 and ZINC000004096987) from the small molecule database (ZINC database) were potential effective agonists of Dopamine receptor. These two compounds can combine with Dopamine receptor with higher affinity and proved to be no toxic. The cell experiment showed that two compounds could inhibit the proliferation and PRL secretion of MMQ cells (pituitary tumor cells). Thus, this study provided valuable information about Dopamine receptor agonist-based drug discovery. So, this study will benefit patients with prolactinoma and Parkinson's disease a lot.
Topics: Biological Products; Bromocriptine; Cell Line, Tumor; Cell Survival; Dopamine Agonists; Drug Evaluation, Preclinical; Humans; Hydrogen Bonding; Ligands; Molecular Docking Simulation; Molecular Dynamics Simulation; Prolactin; Receptors, Dopamine
PubMed: 34170848
DOI: 10.18632/aging.203180 -
Journal of Clinical Medicine Jul 2022A recall for histological pseudocapsule (PS) and reappraisal of transsphenoidal surgery (TSS) as a viable alternative to dopamine agonists in the treatment algorithm of...
A recall for histological pseudocapsule (PS) and reappraisal of transsphenoidal surgery (TSS) as a viable alternative to dopamine agonists in the treatment algorithm of prolactinomas are getting vibrant. We hope to investigate the effectiveness and risks of extra-pseudocapsular transsphenoidal surgery (EPTSS) for young women with microprolactinoma, and to look into the factors that influenced remission and recurrence, and thus to figure out the possible indication shift for primary TSS. We proposed a new classification method of microprolactinoma based on the relationship between tumor and pituitary position, which can be divided into hypo-pituitary, para-pituitary and supra-pituitary groups. We retrospectively analyzed 133 patients of women (<50 yr) with microprolactinoma (≤10 mm) who underwent EPTSS in a tertiary center. PS were identified in 113 (84.96%) microadenomas intraoperatively. The long-term surgical cure rate was 88.2%, and the comprehensive remission rate was 95.8% in total. There was no severe or permanent complication, and the surgical morbidity rate was 4.5%. The recurrence rate with over 5 years of follow-up was 9.2%, and a lot lower for the tumors in the complete PS group (0) and hypo-pituitary group (2.1%). Use of the extra-pseudocapsule dissection in microprolactinoma resulted in a good chance of increasing the surgical remission without increasing the risk of CSF leakage or endocrine deficits. First-line EPTSS may offer a greater opportunity of long-term cure for young female patients with microprolactinoma of hypo-pituitary located and Knosp grade 0-II.
PubMed: 35807204
DOI: 10.3390/jcm11133920 -
Frontiers in Endocrinology 2022Prolactin is a polypeptide hormone that is well known for its role in reproductive physiology. Recent studies highlight its role in neurohormonal appetite regulation and... (Review)
Review
Prolactin is a polypeptide hormone that is well known for its role in reproductive physiology. Recent studies highlight its role in neurohormonal appetite regulation and metabolism. Elevated prolactin levels are widely associated with worsening metabolic disease, but it appears that low prolactin levels could also be metabolically unfavorable. This review discusses the pathophysiology of prolactin related metabolic changes, and the less commonly recognized effects of prolactin on adipose tissue, pancreas, liver, and small bowel. Furthermore, the effect of dopamine agonists on the metabolic profiles of patients with hyperprolactinemia are discussed as well.
Topics: Dopamine Agonists; Humans; Hyperprolactinemia; Pituitary Neoplasms; Prolactin; Prolactinoma
PubMed: 36246929
DOI: 10.3389/fendo.2022.1002320 -
Pituitary Jun 2024Prolactinomas are common tumours that significantly reduce quality-of-life (QOL) due to sellar mass effect, secondary hypogonadism, and the peripheral effects of...
BACKGROUND
Prolactinomas are common tumours that significantly reduce quality-of-life (QOL) due to sellar mass effect, secondary hypogonadism, and the peripheral effects of prolactin. Understanding the factors that influence QOL would provide insights into therapeutic targets to optimise patient outcomes and improve wellbeing in prolactinoma.
METHODS
A systematic review was performed in accordance with the PRISMA statement. Studies that reported patient QoL using validated metrics were included. Bias and methodological rigour were assessed using the MINORS criteria.
RESULTS
A total of 18 studies were identified studies were available for review, comprising 877 patients. Most were small cross-sectional studies at high risk of bias. Prolactinoma exhibit worse QOL than healthy controls, particularly mental and psychosocial wellbeing. QOL is also worse than patients with non-functional adenomas, but better than those with Cushing's disease and acromegaly. QOL correlates with prolactin levels, and approaches population baseline with prolonged biochemical control. Dopamine agonists and surgery both improve overall QOL, however improvements are more rapid with surgery.
CONCLUSION
Poor quality of life in prolactinoma is multifactorial, related to biochemical control, side effects of therapy, and sellar mass effect. Targeting persistent symptoms, reducing healthcare costs, and reducing side-effects of therapy are avenues to improving QOL in patients with prolactinoma.
Topics: Prolactinoma; Humans; Quality of Life; Pituitary Neoplasms; Dopamine Agonists
PubMed: 38656635
DOI: 10.1007/s11102-024-01392-1 -
Indian Journal of Endocrinology and... 2023This study was aimed at determining the frequency of thyroid autoimmunity and subclinical hypothyroidism in patients with hyperprolactinemia due to prolactinoma compared...
BACKGROUND
This study was aimed at determining the frequency of thyroid autoimmunity and subclinical hypothyroidism in patients with hyperprolactinemia due to prolactinoma compared to well-matched healthy controls.
METHODS
This was a cross-sectional study wherein 78 treatment naïve prolactinoma patients and ninety-two healthy control subjects were recruited. Serum prolactin (PRL), thyroid-stimulating hormone (TSH), total thyroxine (T4), circulating anti-thyroid peroxidase (anti-TPO), and anti-thyroglobulin (anti-Tg) antibody levels were measured in all study subjects. Progression of the antibody-positive population to subclinical hypothyroidism was determined.
RESULTS
The median PRL level among patients was 166 ng/ml (IQR 85-467) compared to 11.4 ng/ml (IQR 8.5-15.9) in controls ( < 0.001). There was no significant difference in levels of T4 ( = 0.83) and TSH ( = 0.82) between the cases and controls. Overall, 25% of patients had the presence of anti-thyroid antibodies as compared to 20% of controls ( = 0.56). SCH was more common in antibody-positive hyperprolactinemia subjects compared with antibody-positive controls.
CONCLUSION
We did not find an increased prevalence of thyroid autoimmunity among untreated prolactinoma patients compared to healthy controls. At the same time, subclinical hypothyroidism was more common in thyroid antibody-positive patients with hyperprolactinemia than positive controls.
PubMed: 37215267
DOI: 10.4103/ijem.ijem_425_21 -
Cancers Dec 2019Pituitary adenomas (PAs) are among the most common intracranial neoplasms, but despite their histologically benign nature, these tumors sometimes grow large enough to... (Review)
Review
Pituitary adenomas (PAs) are among the most common intracranial neoplasms, but despite their histologically benign nature, these tumors sometimes grow large enough to cause symptoms of mass effect such as vision loss, headaches, or hypopituitarism. When they get this large, surgery will unfortunately not be curative and, other than prolactinomas, medical options are limited, and radiation has variable efficacy in controlling growth. Understanding the genetic perturbations, such as single nucleotide polymorphisms (SNPs), that promote the formation or growth of functional and nonfunctional PAs is important because such genetic insights could improve the diagnosis and subsequent classification of PAs as well as unlock potential therapeutic targets outside contemporary standard of care. While there have been great strides in the research of SNPs as drivers of PA formation and maintenance, a comprehensive discussion of these genetic mutations has not been undertaken. In the present article, and with the goal of providing scientists and clinicians a central review, we sought to summarize the current literature on SNPs and their relationship to PA formation. Across multiple tumor types, such as nonfunctioning PAs, prolactinomas, corticotroph adenomas, somatotroph adenomas, thyrotropic adenomas, and gonadotroph adenomas, SNPs in cell surface receptors implicated in proliferation can be appreciated. Polymorphisms found in tumor suppressors and cell cycle regulators have also been identified, such as p53 SNPs in nonfunctioning PAs or cyclin D1 in prolactinomas. While the translational relevance of SNPs in the formation of PAs is still in the early stages, the use of wide-scale genomic analysis to identify patients at risk for developing PAs could yield therapeutic benefit in the future.
PubMed: 31818039
DOI: 10.3390/cancers11121977 -
Journal of Cardiology Cases Aug 2023Both peripartum cardiomyopathy (PPCM) and takotsubo syndrome (TTS) are diagnoses of exclusion and are thus considered a heterogeneous disease group. TTS is generally...
UNLABELLED
Both peripartum cardiomyopathy (PPCM) and takotsubo syndrome (TTS) are diagnoses of exclusion and are thus considered a heterogeneous disease group. TTS is generally triggered by psychogenic or physical stress. Recently, the anti-angiogenic factor cleaved prolactin has been noted as a cause of PPCM, but the precise mechanisms of these diseases remain unexplained. An 87-year-old female with a past surgical history, including transsphenoidal endoscopic surgery to remove a pituitary prolactinoma, recently underwent surgery to repair a left-sided femoral neck fracture and developed dyspnea followed by back pain; shortly after, she became embarrassed by fecal incontinence. Her initial electrocardiogram showed T wave inversions with QT prolongation leading to sustained ventricular tachycardia. No obstructive coronary artery disease was found on emergent coronary angiography, and the left ventriculography findings were consistent with TTS. After acute-phase treatment, she was diagnosed with recurrent prolactinoma based on her head magnetic resonance imaging findings. This patient's high levels of prolactin may have played a role in the pathogenesis of TTS.
LEARNING OBJECTIVE
Peripartum cardiomyopathy and takotsubo syndrome (TTS) are diagnosed by exclusion, and their precise mechanisms remain unknown. We present a case of TTS associated with a prolactinoma.
PubMed: 37521571
DOI: 10.1016/j.jccase.2023.04.002 -
Neurology India 2020Functioning pituitary tumors contribute to significant morbidity and mortality. Proper diagnostic approach and management is essential for optimal outcomes.... (Review)
Review
Functioning pituitary tumors contribute to significant morbidity and mortality. Proper diagnostic approach and management is essential for optimal outcomes. Prolactinomas, the commonest of these, are the only tumors which can be managed medically. Acromegaly, apart from acral enlargement, can have multiple comorbidities like diabetes, hypertension, and obstructive sleep apnea. The primary treatment is surgical and it can be supplemented by radiotherapy and medications such as somatostatin analogs, growth hormone receptor blockers, or cabergoline. Thyrotropin-secreting tumors are rare and present with hyperthyroidism. Optimal preoperative management followed by surgical resection often leads to cure.
Topics: Acromegaly; Humans; Pituitary Neoplasms; Prolactinoma; Treatment Outcome
PubMed: 32611888
DOI: 10.4103/0028-3886.287672 -
Annals of Translational Medicine Jul 2020Prolactinoma is the most common hormone-secreting pituitary adenoma. Dopamine receptor agonists (DAs) are effective in reducing prolactin levels and tumor mass, but some...
BACKGROUND
Prolactinoma is the most common hormone-secreting pituitary adenoma. Dopamine receptor agonists (DAs) are effective in reducing prolactin levels and tumor mass, but some prolactinoma patients are resistant to DAs. Treating patients with DA-resistant prolactinoma is challenging. In this study, we examined the anti-prolactinoma effect of artesunate (ART), a potential new treatment option for prolactinoma, and its mechanism of action.
METHODS
Cell Counting Kit-8 (CCK8) and flow cytometry were used to detect the effect of ART on the proliferation, cycle, and apoptosis of rat pituitary adenoma cell line MMQ. The subcellular localization of ART was observed using confocal fluorescence microscopy. The JC-1 mitochondrial membrane potential (MMP) detection and Seahorse assays were used to detect the effect of ART on mitochondrial function. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were used to detect the effect of ART on the expression of prolactin (PRL) and apoptosis-related proteins. A mouse xenograft model of prolactinoma was used to detect the inhibitory effect of ART on MMQ .
RESULTS
ART specifically inhibited MMQ proliferation and PRL synthesis, induced G0/G1 phase arrest and apoptosis . ART accumulated in the mitochondria of MMQ cells, inhibiting mitochondrial respiratory function and mediating apoptosis through the mitochondrial pathway. ART also inhibited proliferation and activated the apoptosis of MMQ cells .
CONCLUSIONS
ART has a strong inhibitory effect on prolactinoma both and , and its effects rely on high MMP to inhibit mitochondrial metabolism and induce apoptosis. Our results provide evidence for ART as a candidate drug for the treatment of prolactinoma.
PubMed: 32793702
DOI: 10.21037/atm-20-1113 -
Journal of Cancer 2021To identify critical roles played by NEK2 in prolactinomas and to clarify the corresponding underlying mechanisms. We performed RNA-seq on MMQ cell lines treated with...
To identify critical roles played by NEK2 in prolactinomas and to clarify the corresponding underlying mechanisms. We performed RNA-seq on MMQ cell lines treated with the dopamine receptor agonist cabergoline (CAB) to identify genes involved in prolactinoma progression and dopamine receptor-agonist (DA) sensitivity. NEK2 was then selected for further study. The expression of NEK2 was examined using quantitative real-time PCR, western immunoblotting, and immunohistochemistry - both in pituitary adenomas (PA) and in normal pituitary tissue. We used gain-of-function and loss-of-function assays to explore the biologic roles of NEK2 in cell growth and . Co-immunoprecipitation was also used to detect the binding between NEK2 and USP7. Herein, we reported that NEK2 was upregulated in prolactinomas, particularly dopamine-resistant prolactinomas. NEK2 overexpression significantly promoted pituitary tumor GH3 and MMQ cell proliferation, and it impaired cellular sensitivity to CAB. Conversely, knockdown of NEK2 inhibited GH3 and MMQ cell growth, and sensitized the cells to CAB. Mechanistically, NEK2 regulated cell proliferation via the Wnt-signaling pathway; and in addition, we demonstrated that USP7 interacted with, deubiquitylated, and stabilized NEK2. Collectively, our results suggest that NEK2 might be a potential therapeutic target for prolactinoma.
PubMed: 33754007
DOI: 10.7150/jca.52937