Journal of Neuroendocrinology最新文献

{"title":"Peptide receptor radionuclide therapy with somatostatin analogs beyond gastroenteropancreatic neuroendocrine tumors","authors":"Giulia Santo,&nbsp;Gianpaolo di Santo,&nbsp;Francesco Cicone,&nbsp;Irene Virgolini","doi":"10.1111/jne.70013","DOIUrl":"10.1111/jne.70013","url":null,"abstract":"<p>First isolated by Brazeau et al. in 1972, somatostatin (SST) is a neuropeptide known for regulating various signaling pathways through its specific cell surface receptors. Somatostatin receptors (SSTRs) comprise a family of five G protein-coupled receptors that are widely distributed across the human body and are expressed by various tumor types. The growing understanding of their clinical potential led to the introduction of both cold and radiolabeled somatostatin analogs (SSAs), which have revolutionized the management of several cancers, especially neuroendocrine tumors. As a direct consequence, advances in peptide receptor radionuclide therapy (PRRT) over the last 30 years led to the approval of ¹⁷⁷Lu-DOTATATE for the treatment of gastroenteropancreatic neuroendocrine tumors (GEPNETs). Theoretically, any cancer patients whose tumors express SSTR, as demonstrated in vivo through SSTR-based molecular imaging, could be candidates for PRRT, especially those with limited treatment options. However, evidence on the efficacy of PRRT in non-GEPNET SSTR-expressing tumors is limited, and mainly derived from small retrospective studies. Given the limited therapeutic options for advanced/metastatic patients, there is a clear need for randomized trials to formally approve PRRT with SSAs for patients who may benefit from this treatment, particularly in certain types of neuroendocrine neoplasms such as lung carcinoids, paragangliomas, and meningiomas, where high rates of disease control (up to 80%) can be achieved. In addition, emerging evidence supports the potential of combination therapies, alpha emitters, and non-SSTR-based radionuclide therapy in tumors beyond GEPNET. This review aims to provide a comprehensive overview of PRRT's role in cancers beyond GEPNET, exploring new possibilities and future directions for most SSTR highly expressing tumors.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"37 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.70013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prostaglandin synthesis mediates the suppression of arcuate Kiss1 neuron activation and pulsatile luteinizing hormone secretion during immune/inflammatory stress in female mice.","authors":"Rodrigo A Carrasco, Jessica Jang, Jacklyn Jung, Richard B McCosh, Michael J Kreisman, Kellie M Breen","doi":"10.1111/jne.70004","DOIUrl":"10.1111/jne.70004","url":null,"abstract":"<p><p>Stress induces a series of compensatory mechanisms with the objective of restoration or adaptation of physiological function. A common casualty of the response to stress is impaired reproduction via the inhibition of pulsatile luteinizing hormone (LH) secretion; however, how stressors convey LH inhibition remains unclear and may be dependent on stress type. Immune/inflammatory stress, modeled with peripheral lipopolysaccharide (LPS) exposure, induces a systemic inflammatory response which may contrast with the neural mechanisms employed by psychosocial stressors. We examined the suppressive effect of LPS versus psychosocial stress, modeled with restraint, on pulsatile LH secretion and investigated the neural mechanisms underlying LPS-induced LH suppression in ovariectomized (OVX) female mice. We observed that both LPS and restraint significantly suppressed mean LH concentrations; however, the dynamics of pulse suppression displayed stress-type dependency. LPS induced a reduction in both LH pulse frequency and amplitude, whereas restraint suppressed LH pulse frequency without compromising pulse amplitude. Next, we investigated the mediatory role of immune/inflammatory signaling for LPS to impair LH secretion and upstream arcuate Kiss1 cell function. Peripheral administration of flurbiprofen, a prostaglandin synthesis inhibitor, blocked the suppressive effect of LPS on LH pulse frequency and amplitude. Interestingly, flurbiprofen only partially prevented the suppressive effect of LPS on arcuate Kiss1 cell activity, as measured by c-Fos expression. These data demonstrate that immune/inflammatory stress inhibits the activity of the LH pulse generator, in part, via a prostaglandin-dependent pathway and supports the role of differential neural mechanisms mediating LH pulse suppression during stress.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e70004"},"PeriodicalIF":3.3,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective changes in vasopressin neurons and astrocytes in the suprachiasmatic nucleus of Prader-Willi syndrome subjects.","authors":"Felipe Correa-da-Silva, Jari B Berkhout, Pim Schouten, Margje Sinnema, Constance T R M Stumpel, Leopold M G Curfs, Charlotte Höybye, Ahmed Mahfouz, Onno C Meijer, Alberto M Pereira, Eric Fliers, Dick F Swaab, Andries Kalsbeek, Chun-Xia Yi","doi":"10.1111/jne.70015","DOIUrl":"https://doi.org/10.1111/jne.70015","url":null,"abstract":"<p><p>The hypothalamic suprachiasmatic nucleus (SCN) hosts the central circadian pacemaker and regulates daily rhythms in physiology and behavior. The SCN is composed of peptidergic neuron populations expressing arginine vasopressin (AVP) and vasoactive intestinal polypeptide (VIP), as well as glial cells. Patients with Prader-Willi Syndrome (PWS) commonly experience circadian disturbances, which are particularly evident in their sleep/wake patterns. Using publicly available single-cell RNA sequencing data, we assessed the cell-type specificity of PWS-causative genes in murine SCN, which revealed the differential presence of PWS-related genes in glial and neural subpopulations. We then investigated neurons and glial cells in the SCN using immunohistochemistry in the postmortem hypothalami of PWS subjects and matched controls. We profiled neural populations characterized by AVP and VIP, astroglia characterized by glial fibrillary acid protein (GFAP), and microglia marked by ionized calcium-binding adapter molecule 1 (Iba1) and NADPH oxidase 2 (NOX2). Our analysis revealed an increased total number, neuronal density, and relative staining intensity of AVP-containing neurons in the PWS compared to controls while VIP-containing cells were unaltered. In contrast, GFAP-expressing astroglial cells were significantly lower in PWS subjects. Moreover, we did not detect any differences in microglia between PWS subjects and controls. Collectively, our findings show that PWS selectively affects AVP-containing neurons and GFAP-expressing astrocytes in the SCN. As each of these cell populations can affect the daily rhythmicity of the SCN biological clock machinery, the disruption of these cells may contribute to the circadian disturbances in patients with PWS.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e70015"},"PeriodicalIF":3.3,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear medicine and perspective thoughts in the diagnosis and treatment of pheochromocytoma and paraganglioma.","authors":"Emirhan Harbi, Michael Aschner","doi":"10.1111/jne.70017","DOIUrl":"https://doi.org/10.1111/jne.70017","url":null,"abstract":"<p><p>Pheochromocytoma and paraganglioma (PPGL) are rare and life-threatening tumors of the adrenal medulla and extra-adrenal paraganglia, respectively. Management of PPGL depends on accurate diagnosis and treatment. This review provides a very comprehensive overview of nuclear medicine in PPGL with some of our perspective views on diagnostic challenges and pitfalls, treatment, and new phase studies. It describes nuclear medicine techniques including ⁶⁴Cu/⁶⁸Ga-DOTA-SSA, ¹⁸F-FDOPA, ¹⁸F-FDG, ¹²³I-MIBG, and some emerging molecular imaging agents and PRRT therapies, such as ²⁰³Pb VMT-α-NET and ²¹²Pb VMT-α-NET targeted alpha therapy (TAT). It also provides insight into the use of proliferating cell nuclear antigen (PCNA) inhibitors in combination with therapeutics in aggressive/metastatic PPGL. Through a comprehensive review of the latest developments and clinical practice, this review aims to guide healthcare professionals in improving the diagnostic accuracy and therapeutic efficacy of PPGL.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e70017"},"PeriodicalIF":3.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A glucocorticoid receptor antagonist affects corticosterone but not neophobia in wild-caught house sparrows (Passer domesticus).","authors":"Marquise S Henry, Melanie G Kimball, Ella B Cochran, Blake A Dusang, William J Frazier, Keegan R Stansberry, Tosha R Kelly, Emily G Stelling, Christine R Lattin","doi":"10.1111/jne.70009","DOIUrl":"https://doi.org/10.1111/jne.70009","url":null,"abstract":"<p><p>Avoidance of novel stimuli (neophobia) affects how wild animals interact with their environment and may partly determine whether animals persist in human-altered landscapes. The neuroendocrine mediators of neophobia are poorly understood, although past work demonstrated that experimentally reducing circulating corticosterone in wild-caught house sparrows (Passer domesticus) decreased neophobia toward novel objects placed near the food dish. In this experiment, we directly tested the role of one of the two types of corticosterone receptors, the glucocorticoid receptor (GR), in mediating neophobia in house sparrows by administering a GR antagonist (RU486, n = 10) or a vehicle control (peanut oil, n = 10) over 5 consecutive days and measuring responses to novel objects both pre- and post-treatment. We also measured baseline and stress-induced corticosterone in all sparrows on the final day of behavior trials. To better understand the effects of RU486 on corticosterone over time, in a separate group of sparrows (n = 12) we administered RU486 or vehicle over 5 days and took multiple blood samples to assess baseline and stress-induced corticosterone. Overall, we did not detect an effect of subcutaneous RU486 injections on neophobia behavior. However, we did find that RU486 injections significantly decreased stress-induced corticosterone levels starting 1 day post-injection and baseline corticosterone levels starting 6 days post-injection, compared to vehicle-injected controls. Our results suggest that GR is not involved in mediating neophobia behavior in house sparrows.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e70009"},"PeriodicalIF":3.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New insights in cellular senescence: The pituitary model.","authors":"Florencia Herbstein, Josefina Rosmino, Mirtha Adriana Guitelman, Joaquina Cagliero, David Gonilski-Pacin, Nicolas Ciancio Del Giudice, Manuel Fiz, Mariana Fuertes, Eduardo Arzt","doi":"10.1111/jne.70008","DOIUrl":"https://doi.org/10.1111/jne.70008","url":null,"abstract":"<p><p>Pituitary tumors are characterized by slow proliferation rates and a high prevalence within the population. The pathogenesis of these tumors remains incompletely understood, although accumulating evidence suggests that the activation of the cellular senescence program, triggered by various stressors and functioning as a brake on cellular proliferation, may contribute to their typically benign nature. Multiple mediators of the senescence response are implicated in this process. Interleukin-6 (IL-6), a proinflammatory cytokine, plays a dual role in pituitary tumor biology. It is involved in both physiological pituitary growth and the senescence-associated secretory phenotype (SASP), where it mediates paracrine-proliferative signals. In addition to its secretory functions, IL-6 has been implicated in the regulation of pituitary senescence through non-secretory mechanisms. Other factors, such as growth hormone (GH), the pituitary tumor-transforming gene (PTTG), and interactions within the tumor microenvironment, including immune cell dynamics, also contribute to the senescence observed in these tumors. This review examines the latest evidence concerning the role of senescence in pituitary tumors, with a particular focus on the contribution of IL-6 to this process.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e70008"},"PeriodicalIF":3.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anatomic distribution of kisspeptin neurons in the adult sheep amygdala: Associations with sex, estrogen receptor alpha, androgen receptor, and sexual partner preference.","authors":"Anna Igler, Rebecka Amodei, Charles E Roselli","doi":"10.1111/jne.70011","DOIUrl":"https://doi.org/10.1111/jne.70011","url":null,"abstract":"<p><p>Kisspeptin neurons are primarily known for regulating reproductive function by stimulating hormone release that controls puberty and fertility. While typically associated with the hypothalamus, recent research suggests their presence in other brain regions, including the amygdala. The amygdala, crucial for emotional processing and social behaviors, consists of various nuclei. However, the specific distribution and potential functional implications of kisspeptin neurons within this region remain unclear. Understanding kisspeptin neuron distribution in the sheep amygdala could provide insights into their roles in modulating reproductive functions, emotional, and social behaviors in a species closely related to humans. This study employed immunohistochemistry and RNAscope™ fluorescent in situ hybridization to map the distribution of kisspeptin fibers and cells in the amygdala of intact adult male and luteal-phase female sheep. The research also investigated the co-expression of Kiss1 with estrogen receptor-α (ESR1) and androgen receptor (AR) mRNA, as well as the presence of kisspeptin receptor (Kiss1r) mRNA-containing cells. Kisspeptin immunoreactive fibers were most dense in the medial amygdala, while Kiss1 mRNA-containing cells were abundant in the medial, cortical, and basal nuclei. Extensive co-expression of Kiss1 with ESR1 and AR mRNA was observed. In the posterior medial nucleus, 80% of kisspeptin neurons co-expressed ESR1, and 40% co-expressed AR. Kiss1r mRNA-containing cells were found in the medial, cortical, and basal nuclei and co-localized within cells expressing Kiss1 mRNA. No differences in kisspeptin cell numbers were found between rams and ewes or between rams with different sexual partner preferences. This study provides a foundational map of the kisspeptin system in the sheep amygdala, offering insights into its potential roles in reproductive, emotional, and social behaviors. The extensive co-expression of Kiss1 mRNA with ESR1 and AR mRNA suggests possible regulation by sex steroids, while the presence of Kiss1r mRNA-containing cells indicates potential autocrine or paracrine signaling. These findings contribute to our understanding of kisspeptin neurons' distribution and potential functions beyond the hypothalamus, particularly in the amygdala.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e70011"},"PeriodicalIF":3.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Critical role of arcuate nucleus kisspeptin and Kiss1R in regulation of the ovine luteinizing hormone surge.","authors":"Max J Griesgraber, Lique M Coolen, Kayla M Onslow, Jacob R Corey, Rachel E Rice, Eliana G Aerts, Elizabeth C Bowdridge, Steven L Hardy, Michael N Lehman, Robert L Goodman, Stanley M Hileman","doi":"10.1111/jne.70010","DOIUrl":"https://doi.org/10.1111/jne.70010","url":null,"abstract":"<p><p>Hypothalamic kisspeptin (Kiss), neurokinin B (NKB), and dynorphin-containing (KNDy) neurons in the arcuate nucleus (ARC) have consistently been shown to be the central generator of gonadotropin-releasing hormone (GnRH) and corresponding luteinizing hormone (LH) pulses in mammals and possibly contribute to surge secretion as well. Additionally, recent evidence from experiments in sheep suggests that ARC Kiss1R-containing neurons play an important role in regulating the timing and amplitude of LH pulses. In this study, we examined the functional role of ARC KNDy and Kiss1R-containing neurons in ovine LH surge secretion via injection of saporin-ligand conjugates (SAP) to ablate these neural populations. NKB-SAP injections significantly reduced the percentage of ARC Kiss1 (~65% decrease) cells compared to control animals, and a surge-like increase of LH was prevented in ewes with the greatest degree of Kiss1 cell ablation. Kiss-SAP injections had no effect on Kiss1 cell percentage or ARC Kiss1R cell number compared to controls, the latter perhaps due to Kiss1R suppression in control animals from elevated estradiol concentrations during the LH surge. However, Kiss-SAP injections consistently and robustly decreased LH surge amplitude, with 80% of Kiss-SAP-treated ewes failing to generate a surge. While the exact identity of these ARC Kiss1R neurons has yet to be fully elucidated, they likely act downstream or in concert with KNDy neurons and possibly integrate other surge-centric signaling pathways to generate the ovine LH surge. These results support the conclusion that KNDy neurons contribute significantly to the ovine LH surge, while ARC Kiss1R neurons appear to be necessary for a functional surge to occur in sheep.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e70010"},"PeriodicalIF":3.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peptide receptor radionuclide therapy (PRRT) special issue","authors":"Shaunak Navalkissoor,&nbsp;Robert P. Millar","doi":"10.1111/jne.70014","DOIUrl":"10.1111/jne.70014","url":null,"abstract":"","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"37 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estrogens produced within the central amygdala inhibit varicella zoster-induced orofacial pain.","authors":"Phillip Kramer, Lauren Nguyen, Paul R Kinchington","doi":"10.1111/jne.70012","DOIUrl":"https://doi.org/10.1111/jne.70012","url":null,"abstract":"<p><p>Varicella zoster virus (VZV) causes chicken pox, and reactivation of this virus later in life causes shingles. Previous work demonstrated that estrogens could reduce VZV-induced orofacial pain and affect gene expression in the central amygdala. It is known that the central amygdala processes pain signals from the orofacial region and that estrogens produced by the enzyme aromatase within the central amygdala regulate neuronal function. Based on the previous studies, it was hypothesized estrogens produced within the central amygdala attenuate VZV-induced orofacial pain. To address this hypothesis, male Long-Evans rats were implanted with cannulas terminating in the central amygdala. Through these cannulas, the aromatase inhibitor letrozole or estrogen receptor alpha (ERα) agonist, 4,4',4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT), was infused in the central amygdala. The whisker pad of each rat was injected with either MeWo cells or MeWo cells containing VZV. One week after VZV injection, letrozole or PPT was infused into the central amygdala, followed by measuring pain behavior, GABA release, and estradiol concentrations. Tissues in the orofacial pain pathway were isolated, and neuronal activity was quantitated by counting c-Fos-positive neurons. Letrozole significantly increased the pain response and decreased GABA release. Letrozole also decreased estradiol within the central amygdala. Infusion of PPT reduced pain and increased GABA release. Moreover, letrozole increased the number of active neurons in the lateral parabrachial nucleus and spinal trigeminal nucleus, while PPT reduced the number of active neurons in the trigeminal ganglia, lateral parabrachial nucleus, and spinal trigeminal nucleus. The results suggest aromatase-derived estradiol interacts with ERα within the central amygdala to attenuate VZV-induced pain by increasing GABA release and reducing neuronal activity in the pain pathway.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e70012"},"PeriodicalIF":3.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}