Eureka 2023! Part II: Top Endocrine Discoveries

For the ninth year running, Endocrine News talks to editors from Endocrine Society publications to unearth the endocrine nuggets of 2023. Here, the editors of Endocrinology weigh in on what they think qualify as the year’s biggest discoveries in endocrine science.

Endocrinology Editor-in-Chief Carol A. Lange, PhD, professor of medicine (Division of Hematology, Oncology, and Transplantation) and pharmacology; Tickle Family Land Grant Endowed Chair of Breast Cancer Research; co-lead, Cellular Mechanisms of Cancer Program; and director, Molecular, Genetic, and Cellular Targets of Cancer Training Program at the University of Minnesota Masonic Cancer Center in Minneapolis chose “Estradiol Augments Tumor-Induced Neutrophil Production to Promote Tumor Cell Actions in Lymphangioleiomyomatosis Models,” by Minor, B. M. N. et al. from the April issue of Endocrinology. Says Lange: “This is really a sweeping mechanistic and translational story that I predict will have a high impact on the field and on patients with lymphangioleiomyomatosis (LAM). Estrogen signaling promotes LAM via activation and expansion of neutrophils within the bone marrow, which in turn drive the disease.”

Lange’s other picks include another great mechanistic study that looks at “the other” estrogen receptor ligands as well as two papers from the John Blenis lab at Weill Cornell that explore “the intersection of aging, metabolism, and cancer and suggest we can modify diet to fight cancer in very impactful ways”:

• “Estrone, the major postmenopausal estrogen, binds ERa to induce SNAI2, epithelial-to-mesenchymal transition, and ER+ breast cancer metastasis,” by Qureshi, R. et al. from the November 2022 issue of Cell Reports

• “Altered propionate metabolism contributes to tumour progression and aggressiveness,” by Gomes, A. P. et al. from the March 2022 issue of Nature Metabolism

• “Tumor-produced and aging-associated oncometabolite methylmalonic acid promotes cancer-associated fibroblast activation to drive metastatic progression,” by Li, Z. et al. from the October 2022 issue of Nature Metabolism

“This is really a sweeping mechanistic and translational story that I predict will have a high impact on the field and on patients with lymphangioleiomyomatosis (LAM). Estrogen signaling promotes LAM via activation and expansion of neutrophils within the bone marrow, which in turn drive the disease.”

Carol A. Lange, PhD, editor-in-chief, Endocrinology

More From the Editors of Endocrinology

Several associate editors of Endocrinology also contributed. Hershel Raff, PhD, FAAAS, FAPS, professor of medicine, surgery, and physiology and professor of Pharmacy School, at the Medical College of Wisconsin (MCW), and director of the Endocrine Research Laboratory at Aurora St. Luke’s Medical Center, in Milwaukee chose “Vasopressin Expressed in Hypothalamic CRF Neurons Causes Impaired Water Diuresis in Secondary Adrenal Insufficiency” from the August issue of Endocrinology by Yamagata, S. et al.

“Impaired free water excretion and hyponatremia are common clinical findings in patients with secondary adrenal insufficiency,” Raff says. “Using adrenalectomized AVP-floxed mice, this group demonstrated the novel finding that CRF neurons in the PVH are responsible for the pathogenesis of impaired water excretion in secondary adrenal insufficiency.”

Raff’s honorable mentions include:

• “Hybrid Functional Polymer-Enabled Multiplexed Chemosensor Patch for Wearable Adrenocortex Stress Profiling,” by Yeasmin, S. et al. from the October issue of ACS Applied Material Interfaces

• “Integrative neurocircuits that control metabolism and food intake,” by Brüning, J.C. and Fenselau, H. from the September issue of Science

• “High-resolution daily profiles of tissue adrenal steroids by portable automated collection,” by Upton, T. J. et al. from the June issue of Science Translational Medicine

• “Hormone-mediated neural remodeling orchestrates parenting onset during pregnancy ,” by Ammari, R. et. al from the October issue of Science

Patricia L. Brubaker, PhD, FRSC, professor, Departments of Physiology and Medicine; Banting & Best Distinguished Scholar at the University of Toronto, in Ontario, credits “Enhanced Endosomal Signaling and Desensitization of GLP-1R vs GIPR in Pancreatic Beta Cells,” by Manchanda, Y. et al., published in Endocrinology in May.

“Current interest in the use GLP-1-, GLP-1/GIP- and GLP-1/GIP/GCG-agonist therapy for type 2 diabetes and obesity is extremely high,” Brubaker says. “This paper enhances our understanding of the actions of GLP-1 and GIP through elucidation of their differential receptor dynamics in pancreatic beta cells.”

David R. Grattan, PhD, of the University of Otago, in Dunedin, New Zealand, gave “Warm Responsive Neurons in the Hypothalamic Preoptic Area are Potent Regulators of Glucose Homeostasis in Male Mice,” by Deem, J. D. et al., published in Endocrinology in July, top billing. Grattan says, “This paper shows how elevation in ambient temperature can have dramatic effects on glucose homeostasis, mediated by specific thermoregulatory circuits in the hypothalamus. This provides mechanistic understanding for why glucose tolerance and type 2 diabetes are more common in warmer climates. In a world threatened by global climate change, it is important to understand how rising temperature can influence these critical homeostatic circuits.”

Grattan’s honorable mentions go to two additional Endocrinology “studies that cast light onto longstanding questions about how stress and nutrient availability can influence reproduction”:
• “Hypothalamic PVN CRH Neurons Signal Through PVN GABA Neurons to Suppress GnRH Pulse Generator Frequency in Female Mice,” by McIntyre, C. et al. from June

• “Fasting Modulates GABAergic Synaptic Transmission to Arcuate Kisspeptin Neurons in Female Mice,” by Mansano, N. D. S. et al. from November

Najiba Lahlou, MD, PhD, of the Paris Descartes University in France particularly appreciated the work of Costaglio, S. and Romitti, M., with “Progress Toward and Challenges Remaining for Thyroid Tissue Regeneration,” published in Endocrinology in August her number one pick.

For Lahlou, other work from the broader Costaglio team complements this study, including “Emerging technologies in thyroid biology: Pushing the frontiers of thyroid research,” published in Molecular and Cellular Endocrinology in May, and “Thyroid-on-a-Chip: An Organoid Platform for In Vitro Assessment of Endocrine Disruption,” from Advanced Healthcare Materials in March.

For honorable mentions, Lahlou chose “New Horizons: Gonadotropin-Releasing Hormone and Cognition,” out in the November 2023 in JCEM by Prévot, V; Tena-Sempere, M; and Pitteloud, N., as well as a trio of studies from the Michel Salzet team:
• “Pan-Genomic Regulation of Gene Expression in Normal and Pathological Human Placentas,” by Apicelle, C. et al. from the February issue of Cells

• “Challenges in glioblastoma research: focus on the tumor microenvironment,” by Bikfalvi, A, et al. from the January issue of Trends in Cancer

• “Neurotrauma investigation through spatial omics guided by mass spectrometry imaging: Target identification and clinical applications,” by Mallah, K. et al. from the January issue of Mass Spectrometry Reviews

 Horvath is a Baltimore, Md.-based freelance writer, a frequent and prolific contributor to Endocrine News, and has compiled and written the annual “Eureka!” articles annually for nine years.