Lactotroph Cells Research Articles

The role of prolactin/vasoinhibins in cardiovascular diseases.

Prolactin (PRL) is a polypeptide hormone that is mainly synthesized and secreted by the lactotroph cells of the pituitary. There are two main isoforms of PRL: 23-kDa PRL (named full-length PRL) and vasoinhibins (including 5.6-18 kDa fragments). Both act as circulating hormones and cytokines to stimulate or inhibit vascular formation at different stages and neovascularization, including endothelial cell proliferation and migration, protease production, and apoptosis. However, their effects on vascular function and cardiovascular diseases are different or even contrary. In addition to the structure, secretion regulation, and signal transduction of PRL/vasoinhibins, this review focuses on the pathological mechanism and clinical significance of PRL/vasoinhibins in cardiovascular diseases.

Prolactin and its significance in the placenta.

Prolactin, a pituitary hormone that was discovered about 80years ago and is primarily known for its functions in mammary gland development and lactation, is now known to participate in numerous functions across different phylogenetic groups. Fundamentally known for its secretion from lactotroph cells in adenohypophysis region of pituitary gland, newer studies have demonstrated a number of extrapituitary sites which secrete prolactin, where it acts in an autocrine, paracrine, and endocrine manner to regulate essential physiological and biochemical processes. These sites include lymphocytes, epithelial cells of lactating mammary glands, breast cancer cells of epithelial origin, and the placenta. The placenta is one of the most important organs secreting prolactin; however, its role in placental biology has not to date been reviewed comprehensively. This review elaborates upon the various facets of prolactin hormone, including prolactin production and its post-translational modifications and signaling. Major emphasis is placed on placental prolactin and its potential roles, ranging from the role of prolactin in angiogenesis, preeclampsia, maternal diabetes, and anti-apoptosis, among others.

Abstract #1185225: Hyperprolactinemia in a Transgender Male: A unique etiology

Prolactin is a hormone which is primarily synthesized and secreted by lactotroph cells located in the anterior pituitary gland. Hyperprolactinemia, which is excess levels of Prolactin, may be caused by a number of etiologies including pathologic, functional, drug-related, or physiologic. We report a cause of a transgender male with hyperprolactinemia with no obvious etiology.

Rational Evaluation and Treatment of Prolactinomas: A Concise Review

AbstractProlactinoma is the most common pituitary tumor. It arises from the lactotroph cells and leads to a hyperprolactinemia state. The clinical presentation of prolactinomas is either due to the high prolactin state or the adenoma mass effect. Diagnosis of prolactinomas starts with the confirmation of persistent pathologic hyperprolactinemia. Subsequently, pituitary MRI is required to characterize the prolactinoma size and extension within the sella turcica. Further investigation may include visual field assessment and laboratory investigations for hypopituitarism. Prolactinoma management is mainly medical with dopamine agonists as most of these tumors are responsive. Surgical intervention is rarely required with specific indications.

Decipher the inhibitory potential of phytocompounds from Leptadenia reticulata on dopamine D2 receptor to enhance prolactin secretion.

Dopamine is secreted by the hypothalamus, which inhibits the proliferation and effectiveness of lactotroph cells that release prolactin via dopamine D2 receptor (D2R). D2R activation inhibits lactotroph cell prolactin synthesis and regulates prolactin gene expression. Although, commercial medications are available for hypogalactia and agalactia, various plant sources significantly alleviate these problems. Leptadenia reticulata (Jivanti) is one of the important medicinal plants often consumed by nursing mothers to improve breast milk production. However, mechanism and chemical constituents involved in the inhibition of D2R by Jivanti is unclear. Therefore, in this study the phytocompounds reported from Jivanti were used for in-silico analysis to predict D2R inhibitory potential. The binding affinity value of campesterol and β-sitosterol (- 10.1 and -10.0 kcal/mol) with D2R has high revealed by molecular docking and stable interaction reveled by molecular dynamics simulation. Thus, these lead compounds could exert more D2R inhibitory activity resulting into prolactin release, which may lead to an increase in breast milk production. Although all selected compounds had fine permeation, non-toxic, and non-carcinogenic characteristics predicted by ADMET, campesterol had good solubility, absorption characteristics compared to other. Therefore, Jivanti, which is traditionally known medicinal plant, could be explored as a medication candidate to boost breast milk production.

Prolactin and its receptor: From animal models to pituitary pathophysiology

Prolactin (PRL) is a polypeptide hormone that is mainly synthesized and secreted by lactotroph cells of the anterior pituitary gland. The actions of prolactin are mediated by its transmembrane receptor, PRLR. The principal role attributed to PRL is to stimulate the proliferation and differentiation of the mammary cells required for lactation, but studies of animal models have assigned more than 300 separate actions to this hormone in various species. Hyperprolactinaemia is the prototypical pathological state associated with this hormone. Indeed, hyperprolactinaemia is the most common cause of amenorrhoea due to hypogonadotropic anovulation and is one of the most prevalent endocrine causes of infertility in women. In recent years, the study of conditional or complete Prlr -/- mouse models had improved the understanding concerning the regulation of gonadotroph and lactotroph axes. It is now demonstrated that prolactin exerts autocrine or paracrine actions on lactotroph cells in vivo. One of the major advances was to better understand, using mouse models, the impact of hyperprolactinemia on gonadotroph axis. It is now accepted that hypogonadotropic hypogonadism in patients with hyperprolactinemia is mediated by a decrease of hypothalamic kisspeptin secretion. Gonadotroph axis can be restored by intravenous administration of kisspeptin. However, the mechanisms of lactotroph tumorigenesis in Prlr -/- animals remain incompletely understood and transposable to the human species, since the only patient with biallelic PRLR loss-of-function mutation leading to complete prolactin resistance that has been described so far did not have pituitary adenoma visible on MRI.

Can clinical parameters of patients, sans serum prolactin measurement, identify amenorrhea associated with risperidone use? Results from a cross-sectional analytical study

Background: Risperidone is a second-generation antipsychotic, which exerts its action by antagonizing dopamine (D2) and serotonin (5-HT2A) receptors. Amenorrhea is a common adverse effect observed in risperidone. Risperidone blocks the dopamine receptor of lactotroph cells of the pituitary gland, resulting in loss of the inhibitory effect of dopamine on prolactin. The resultant hyperprolactinemia decreases estrogen through its impact on the pulsatile secretion of gonadotropins and ovarian follicular growth leading to amenorrhea. Identifying the associated clinical parameters will aid in predicting the occurrence of amenorrhea in patients on treatment with risperidone, especially in a setting devoid of prolactin estimation. The objective of this study was to compare the clinical profile of patients with and without risperidone-induced amenorrhea.Methodology: A cross-sectional comparative study was done in a tertiary care hospital. A total of 30 female patients on risperidone who developed amenorrhea were recruited, and age-matched patients on risperidone without amenorrhea were taken as controls. The clinical parameters of the groups were compared using the Mann–Whitney U-test. Binary logistic regression was used to predict the clinical predictors associated with risperidone-induced amenorrhea.Results: The amenorrhea group had a significantly longer duration of untreated psychosis (DUP) (P = 0.011), duration of total treatment (P = 0.003), and duration of treatment exclusively with risperidone (P = 0.002). No significant differences were noted in the dose of risperidone (P = 0.570) and the diagnosis (P = 0.455) between the groups. However, the regression test did not confer any risk due to any clinical parameters.Conclusion: Individuals who developed amenorrhea had a longer DUP and a longer duration of treatment exclusively with risperidone.

Perinatal DEHP exposure modulates pituitary estrogen receptor α and β expression altering lactotroph and somatotroph cell growth in prepuberal and adult male rats

Phthalates are synthetic chemicals widely used to make polyvinylchloride (PVC) soft and flexible. Of these, Di-(2-ethylhexyl) phthalate (DEHP) is the most commonly used, with high human exposure occurring as early as the fetal developmental stage and affecting the endocrine system. We focused on the perinatal DEHP effects on pituitary estrogen receptor (ER) expression in male rats, explored their impact on lactotroph and somatotroph cell growth, and evaluated the direct effects of this phthalate on pituitary cell cultures. Our results showed that DEHP perinatal exposure was unable to modify the ERα+ pituitary cell number from prepuberal rats, but increased ERβ+ cells. In adulthood, the pituitary ERα+ cells underwent a slight decrease with ERβ showing the greatest changes, and with a significant increase observed in somatotroph cells. Also, in vitro, DEHP reduced the ERα+ cells, increased the percentage of ERβ+ pituitary cells and modified the Ki67 index, as well as decreasing the lactotrophs and increasing the somatotroph cells. In conclusion, the present study showed that DEHP induced ER expression changes in normal pituitary glands from male rats in in vivo and in vitro conditions, suggesting that DEHP could differentially modulate lactotroph and somatotroph cell growth, possibly as a consequence of ER imbalance.

Anastrozole as add-on therapy for cabergoline-resistant prolactin-secreting pituitary adenomas: real-life experience in male patients

IntroductionProlactin-secreting adenoma (PRLoma) can present as large and invasive neoplasm, with increased markers of cellular proliferation. First-line approach is Dopamine Agonists (DAs) treatment; however, DA-resistance has been reported, especially in male patients. Estrogens induce lactotroph cell replication and PRL secretion: the use of anti-estrogen treatment in patients with PRLoma have been described in few cases. We reported our experience regarding treatment with the aromatase inhibitor anastrozole (ANA) as add-on therapy for male patients with DA resistant PRLoma.Materials and methodsWe describe four male patients (26, 38, 29 and 19 years old at diagnosis), with PRLoma (median diameter 26 mm, PRL 7730 μg/L). They were resistant to cabergoline (CAB, > 2 mg/week) in terms of PRL secretion and tumor size reduction. ANA 1 mg/day was added to the maximum tolerated dose of CAB for at least 1 year. Magnetic Resonance was performed at baseline, after 6 months of CAB + ANA combination and every 12 months afterward.ResultsPRL levels decreased in all patients after CAB + ANA (mean − 70%, range − 44/− 97%), achieving a normalization of PRL levels in one case. Tumor size decreased in all cases (mean − 47%, range − 24.5/− 68%). No severe adverse effects have been reported, a moderate weight gain has been observed in two cases.ConclusionsAddition of an aromatase inhibitor (ANA) to the dopamine agonist therapy improved the control of prolactin levels and induced tumour regression.

Analytical platforms Vitros ECi 3600 and Cobas 6000: comparative analysis of prolactin measurement.

Prolactin is a polypeptide hormone secreted by the lactotrophic cells of the anterior pituitary gland and has a wide range of biological effects in the human body. Accurate measurements of prolactin concentration are essential in obtaining biochemical data to support clinical decisions in the diagnosis, treatment and prevention of diseases of the pituitary gland, reproductive, immune and other body systems. The aim of our study is to carry out a comparative analysis of the serum prolactin measurement determined by the two analytical platforms Vitros ECi 3600 (Ortho-Clinical Diagnostics) and Cobas 6000 (Roche). Serum samples from 664 patients undergoing examination at the Endocrinology Research Center were included in the study. Comparative analysis of serum prolactin measurement showed that results obtained by the two analytical systems are consistent with each other (r = 0.89, p<0,05). Clinically accuracy of prolactin measurement and to a large extent using the same method is of particular importance in primary diagnosis, treatment and long-term follow-up of the patient.

Psychotic Symptoms Subsequent to Chronic Untreated Prolactinoma: A Case Report

Prolactinomas are prolactin-secreting pituitary tumors originating from the lactotroph cells of the anterior pituitary gland. With hyperprolactinemia, prolactinoma patients may present symptoms of galactorrhea, amenorrhea, sexual dysfunction, and infertility, as well as symptoms due to tumor expansion. Moreover, high level of prolactin effects on mood and behavior thus may lead to depression, anxiety, and hostility through unknown mechanisms. A couple of previous case reports described psychotic disorders in patients with prolactinoma, but none of them came from Chinese population. The case presented here is a 24-year-old unmarried woman presenting psychotic symptoms and amenorrhea following menstrual irregularity. Her psychotic symptoms were intermittent and distressed her for 10 months. Her amenorrhea persisted for several years without a standardized therapy. A suspected prolactinoma was confirmed by a high level of serum prolactin and a brain MRI scanning showing a pituitary macroadenoma. Her psychotic symptoms were treated with olanzapine and psychotherapy during hospitalization. She has been maintained on aripiprazole, bromocriptine, and benzhexol after discharge. Olanzapine is effective and safe in treating psychotic symptoms resulting from hyperprolactinemia. Combination of aripiprazole and bromocriptine are a good option for the maintenance of patients with comorbid psychotic symptoms and prolactinoma.

MicroRNA-7a2 Regulates Prolactin in Developing Lactotrophs and Prolactinoma Cells.

Prolactin production is controlled by a complex and temporally dynamic network of factors. Despite this tightly coordinated system, pathological hyperprolactinemia is a common endocrine disorder that is often not understood, thereby highlighting the need to expand our molecular understanding of lactotroph cell regulation. MicroRNA-7 (miR-7) is the most highly expressed miRNA family in the pituitary gland and the loss of the miR-7 family member, miR-7a2, is sufficient to reduce prolactin gene expression in mice. Here, we used conditional loss-of-function and gain-of-function mouse models to characterize the function of miR-7a2 in lactotroph cells. We found that pituitary miR-7a2 expression undergoes developmental and sex hormone-dependent regulation. Unexpectedly, the loss of mir-7a2 induces a premature increase in prolactin expression and lactotroph abundance during embryonic development, followed by a gradual loss of prolactin into adulthood. On the other hand, lactotroph development is delayed in mice overexpressing miR-7a2. This regulation of lactotroph function by miR-7a2 involves complementary mechanisms in multiple cell populations. In mouse pituitary and rat prolactinoma cells, miR-7a2 represses its target Raf1, which promotes prolactin gene expression. These findings shed light on the complex regulation of prolactin production and may have implications for the physiological and pathological mechanisms underlying hyperprolactinemia.

Hyperprolactinemia and Galactorrhea Associated with Risperidone-Fluoxetine Combination Therapy: A Case Report

Prolactin is a polypeptide hormone secreted and released by lactotroph cells in the anterior pituitary gland in response to diverse physiological stimuli, principally via the inhibitory action of dopamine and serotonin. This paper describes a 44-year-old woman with depression and obsessive-compulsive disorder (OCD) who called the 13-Aban drug and poison information center (DPIC). She was being treated with fluoxetine (80 mg/day) for 10 months until risperidone was added to her regimen for augmentation therapy (0.5 mg/day). Her symptoms improved within less than two months without significant side effects until she experienced painful bilateral breast discharge along with spotting and menstrual irregularity, besides amenorrhea for the previous 2 cycles and serum prolactin level of 33.7 ng/mL, presenting hyperprolactinemia. After discontinuing risperidone, within two weeks, galactorrhea and breast pain disappeared and amenorrhea resolved. Further prolactin level measurement showed the significant reduction. This neuroendocrine effect observed with very low-dose risperidone plus fluoxetine is apparently exerted through both pharmacokinetic and pharmacodynamic augmentation of this combination therapy.

Protocolo diagnóstico de la hiperprolactinemia

Prolactin hormone is mainly secreted by lactotroph cells of adenohypophyses. As consequence, the causes of hyperprolactinemia are almost exclusively physiological and pathological, triggering lactotroph cells prolactin hypersecretion. Clinically hyperprolactinemia is easily recognizable. In women symptoms are menstrual cycle disorders and galactorrhea; in men decreased libido and erectile dysfunction is observed. Diagnosis is performed by the measurement of serum prolactin levels above normal range (> 20 ng/ml in men and in post-menopausal women, and >25 ng/ml in pre-menopausal women). Once diagnosis is confirmed, cause has to be identified. Because in the most cases the etiology is prolactinoma or other disorder of the pituitary fossa (excluded physiologic or pharmacologic causes), neuro-imaging test of the hypothalamic-pituitary region has to be performed.

Surgical Complications of Endoscopic Endonasal Trans-Sphenoidal Approach for Pituitary Tumors

Background: Pituitary macro-adenomas form about 10% of intracranial tumors. Most of them are non-functioning and manifestations are due to space-occupying effects or clinical hypo-pituitarism. Functioning adenomas result in the conditions of Cushing’s disease, galactorrhoea/oligo/amenorrhoea and acromegaly. Non-functioning pituitary tumors may also produce hyper-prolactinaemia due to dis-inhibition of the effects of hypothalamic dopamine on lactotroph cells. Aim of the work: Detection of surgical complications of endoscopic endo-nasal trans-sphenoidal surgery for pituitary tumors and how to avoid and manage them. Material and Methods: This study is conducted upon 40 cases diagnosed to have pituitary tumors, operated upon in department of Neurosurgery at Al-Azhar University Hospitals, and Shibin Al.Kawm teaching hospital from March 2017 to March 2019. prospectively collected and retrospectively analyzed. Results: 11 patients suffered complications, as CSF leak, intra-operative bleeding, and herniation of diaphragm sellae. Conclusions: Endoscopic Trans-sphenoidal approach usually is the method of choice for treating pituitary tumors due to lower risk of complications.

Beta-Arrestin 2 Is Required for Dopamine Receptor Type 2 Inhibitory Effects on AKT Phosphorylation and Cell Proliferation in Pituitary Tumors

Dopamine receptor type 2 (DRD2) agonists are the first-choice treatment for prolactin-secreting pituitary tumors but are poorly effective in nonfunctioning pituitary neuroendocrine tumors (NF-PitNETs). DRD2 reduces AKT phosphorylation in lactotrophs, but no data are available in NF-PitNETs. DRD2 effects on AKT are mediated by a β-arrestin 2-dependent mechanism in mouse striatum. The aim of this study was to investigate DRD2 effects on AKT phosphorylation and cell proliferation in human primary cultured NF-PitNET cells and in rat tumoral lactotroph cells MMQ, and to test β-arrestin 2 involvement. We found that the DRD2 agonist BIM53097 induced a reduction of the p-AKT/total-AKT ratio in MMQ (–32.8 ± 17.6%, p < 0.001 vs. basal) and in a subset (n = 15/41, 36.6%) of NF-PitNETs (subgroup 1). In the remaining NF-PitNETs (subgroup 2), BIM53097 induced an increase in p-AKT. The ability of BIM53097 to reduce p-AKT correlated with its antimitotic effect, since the majority of subgroup 1 NF-PitNETs was responsive to BIM53097, and nearly all subgroup 2 NF-PitNETs were resistant. β-Arrestin 2 was expressed in MMQ and in 80% of subgroup 1 NF-PitNETs, whereas it was undetectable in 77% of subgroup 2 NF-PitNETs. In MMQ, β-arrestin 2 silencing prevented DRD2 inhibitory effects on p-AKT and cell proliferation. Accordingly, β-arrestin 2 transfection in subgroup 2 NF-PitNETs conferred to BIM53097 the ability to inhibit both p-AKT and cell growth. In conclusion, we demonstrated that β-arrestin 2 is required for DRD2 inhibitory effects on AKT phosphorylation and cell proliferation in MMQ and NF-PitNETs, paving the way for a potential role of β-arrestin 2 as a biomarker predicting NF-PitNETs’ responsiveness to treatment with dopamine agonists.

The phthalate DEHP modulates the estrogen receptors α and β increasing lactotroph cell population in female pituitary glands

Humans are exposed to numerous endocrine disruptors on a daily basis, which may interfere with endogenous estrogens, with Di-(2-ethylhexyl) phthalate (DEHP) being one of the most employed. The anterior pituitary gland is a target of 17β-estradiol (E2) through the specific estrogen receptors (ERs) α and β, whose expression levels fluctuate in the gland under different contexts, and the ERα/β index is responsible for the final E2 effect. The aim of the present study was to evaluate in vivo and in vitro the DEHP effects on ERα and β expression in the pituitary cell population, and also its impact on lactotroph and somatotroph cell growth.Our results revealed that perinatal exposure to DEHP altered the ERα and β expression pattern in pituitary glands from prepubertal and adult female rats and increased the percentage of lactotroph cells in adulthood. In the in vitro system, DEHP down-regulated ERα and β expression, and as a result increased the ERα/β ratio and decreased the percentages of lactotrophs and somatotrophs expressing ERα and β. In addition, DEHP increased the S + G2M phases, Ki67 index and cyclin D1 in vitro, leading to a rise in the lactotroph and somatotroph cell populations. These results showed that DEHP modified the pituitary ERα and β expression in lactotrophs and somatotrophs from female rats and had an impact on the pituitary cell growth. These changes in ER expression may be a mechanism underlying DEHP exposure in the pituitary gland, leading to cell growth deregulation.

OR06-03 Serotonin Regulates Corticotroph Tumor Cell Proliferation and ACTH Secretion

Serotonin (5-HT) is an important hormonal modulator and neurotransmitter, and 5-HT has been demonstrated in pituitary tissue from several species. Previous responses to 5-HT antagonists have been reported in some patients with Cushing disease although this effect was unsustained, and ACTH and cortisol levels actually increased in some patients. To better understand the role of serotonin in the regulation of corticotroph tumor growth and ACTH secretion, we first measured serotonin levels in supernatants (SNs) derived from murine corticotroph tumor AtT20 cells. We demonstrated that AtT20 cells secrete serotonin (2±0.05ng/105cells/24h) which was ~50% of the levels secreted by the serotonin secreting mid-gut carcinoid BON-1 cell-line (4.2±0.05ng/105cells/24h). In contrast, serotonin secretion was not detected in rat pituitary tumor lactotroph (GH3) or human embryonic kidney (HEK293) cell SNs, or in our Ham’s F12 medium control. Immunocytochemical staining using serotonin specific antibodies demonstrated that serotonin was diffusively present in AtT20 cell cytoplasm, suggesting that serotonin was endogenously generated in the AtT20 cells. Using real-time PCR, we demonstrated that both serotonin synthesis enzymes, tyrosine hydroxylase-1 (THP1) and -2 (THP2) are expressed in AtT20 cells with higher relative THP1 expression, confirming endogenous corticotroph pituitary tumor serotonin production. We further demonstrated that the synthetic glucocorticoid Dexamethasone (100nM x 24h) suppressed TPH1 expression and inhibited corticotroph tumor serotonin secretion. We next evaluated the actions of serotonin and various serotonin antagonists on corticotroph tumor cell proliferation and ACTH secretion. Ritanserin (10-5M) inhibited murine corticotroph tumor proliferation by 5% and inhibited ACTH secretion by ~25%. In contrast, metergoline (10-5M) and the orally administered TPH inhibitor, telotristat etiprate (10-5M for 1-3 days), inhibited ACTH secretion by 50% and 30% respectively but did not reduce cell proliferation, suggesting that Metergoline and telotristat may regulate ACTH secretion independently of their anti-proliferative effect. Addition of serotonin (10-4~10-5M) to corticotroph tumor cells cultured in reduced serum (OptiMEM) or no serum conditions, resulted in an 80% increase in cell proliferation but had little effect on ACTH secretion with a 1-4% increase. In summary, we have demonstrated that serotonin is synthesized in and secreted from corticotroph tumor cells and that serotonin plays a role in regulation of corticotroph tumor proliferation and ACTH secretion in vitro. Our findings using inhibitors of serotonin action indicate potential for targeting this pathway as a novel treatment for patients with CD.

SAT-312 Beta-Arrestin 2 Is Required for Dopamine Receptor Type 2 Inhibitory Effects on Akt Phosphorylation and Cell Proliferation in Pituitary Tumors

Dopamine receptor type 2 (DRD2) agonists are the first-choice treatment for PRL-secreting pituitary tumors but are poorly effective in non-functioning pituitary neuroendocrine tumors (NF-PitNETs). DRD2 reduces AKT phosphorylation in lactotrophs, but no data are available in NF-PitNETs. DRD2 effects on AKT are mediated by a β-arrestin 2-dependent mechanism in mouse striatum.The aim of this study was to investigate DRD2 effects on AKT phosphorylation and cell proliferation in human primary cultured NF-PitNET cells and in rat tumoral lactotroph cells MMQ, and to test β-arrestin 2 involvement.We found that DRD2 agonist BIM53097 induced a reduction of p- AKT /total-AKT ratio in MMQ (-32.8±17.6%, p<0.001 vs basal) and in a subset (n=15/41,36.6%) of NF-PitNETs (subgroup 1). In the remaining NF-PitNETs (subgroup 2), BIM53097 induced an increase of p- AKT. The ability of BIM53097 to reduce p-AKT correlated to its antimitotic effect, since the majority of subgroup 1 NF-PitNETs was responsive to BIM53097 and nearly all subgroup 2 NF-PitNETs were resistant. β-arrestin2 was expressed in MMQ and in 80% of subgroup 1 NF-PitNETs, whereas it was undetectable in 77% of subgroup 2 NF-PitNETs.In MMQ, β-arrestin 2 silencing prevented DRD2 inhibitory effects on p-AKT and cell proliferation. Accordingly, β-arrestin 2 transfection in subgroup 2 NF-PitNETs conferred to BIM53097 the ability to inhibit both p-AKT and cell growth.In conclusion, we demonstrated that β-arrestin 2 is required for DRD2 inhibitory effects on AKT phosphorylation and cell proliferation in MMQ and NF-PitNETs, paving the way for a potential role of β-arrestin 2 as a biomarker predicting NF-PitNETs responsiveness to treatment with dopamine agonists.

How to Classify the Pituitary Neuroendocrine Tumors (PitNET)s in 2020.

Adenohypophyseal tumors, which were recently renamed pituitary neuroendocrine tumors (PitNET), are mostly benign, but may present various behaviors: invasive, “aggressive” and malignant with metastases. They are classified into seven morphofunctional types and three lineages: lactotroph, somatotroph and thyrotroph (PIT1 lineage), corticotroph (TPIT lineage) or gonadotroph (SF1 lineage), null cell or immunonegative tumor and plurihormonal tumors. The WHO 2017 classification suggested that subtypes, such as male lactotroph, silent corticotroph and Crooke cell, sparsely granulated somatotroph, and silent plurihormonal PIT1 positive tumors, should be considered as “high risk” tumors. However, the prognostic impact of these subtypes and of each morphologic type remains controversial. In contrast, the French five-tiered classification, taking into account the invasion, the immuno-histochemical (IHC) type, and the proliferative markers (Ki-67 index, mitotic count, p53 positivity), has a prognostic value validated by statistical analysis in 4 independent cohorts. A standardized report for the diagnosis of pituitary tumors, integrating all these parameters, has been proposed by the European Pituitary Pathology Group (EPPG). In 2020, the pituitary pathologist must be considered as a member of the multidisciplinary pituitary team. The pathological diagnosis may help the clinician to adapt the post-operative management, including appropriate follow-up and early recognition and treatment of potentially aggressive forms.