Pituitary tumours are intracranial neoplasms that pose significant clinical challenges due to their potential for recurrence, therapeutic resistance and resultant endocrine dysfunction and mass effects. In the normal anterior pituitary, resident pituitary stem cells (PSCs) contribute to tissue homeostasis and cellular turnover. The extent to which PSCs contribute to tumourigenesis is not known, but an increasing number of studies have been aiming to address this. In this review, we summarise current evidence implicating PSCs and tumour stem-like populations in pituitary tumour biology, including potential roles in tumour initiation, maintenance and progression. We outline practical criteria for defining TSCs and evaluate findings from functional studies of human tumours, emerging single-cell and spatial transcriptomic datasets and murine lineage-tracing models. We also provide a curated overview of published single-cell RNA sequencing studies of pituitary tumours, highlighting reported stem/progenitor populations and transcriptional signatures across tumour subtypes and propose a framework for future genomic analyses. Finally, we discuss the translational implications of these findings, including the potential for targeting stem-like populations and their associated signalling pathways.

Tris(2-chloroethyl) phosphate (TCEP) is a widely used chlorinated organophosphorus flame retardant, that has been frequently detected in aquatic organisms and surface water. While previous studies have shown the potential endocrine disrupting effects of TCEP, its long-term reproductive toxicities at environmentally relevant concentrations remain unclear. This study comprehensively analyzed the reproductive toxicity and mechanisms of TCEP in zebrafish. Zebrafish were exposed to TCEP (0.2-200 µg/L) from embryo to adult stages for 120 days. Results showed significant alterations in reproductive indicators, including decreased body length and weight, reduced tissue indices and impaired gonadal development. Notably, TCEP altered sex hormone levels, with decreased 17β-estradiol (E2) and vitellogenin (VTG) in females, increased E2 and VTG in males, and reduced testosterone in both sexes. A female-biased sex ratio was observed at 22.01 and 241.84 µg/L TCEP, with reduced spawning and impaired F1 offspring development. Transcriptomic analysis revealed significant alterations in hypothalamus-pituitary-gonad-liver (HPGL) axis gene expression, such as hsd17b12a. Molecular docking simulations suggested that TCEP may interfere with sex hormone receptor binding and cytochrome P450 (CYP450) enzyme function. This study reveals new insights into the reproductive toxicity mechanisms of TCEP in zebrafish. The toxic effects follow an inverted U-shaped curve, with peak toxicity occurring at approximately 2.62 µg/L. These findings underscore the importance of regulating this emerging contaminant in freshwater ecosystems.

Dysregulation of physiological stress systems, including the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS), is considered the pathway that links child maltreatment with psychopathology. However, how child maltreatment is linked with the coordination of the HPA axis and ANS stress responses remains unclear, particularly during the critical developmental period such as adolescence. This study investigated the association between the HPA axis indexed by cortisol and the ANS indexed by cardiovascular stress responses among adolescents with and without child maltreatment. The Childhood Trauma Questionnaire was administered to 116 adolescents (59 in the child maltreatment group and 57 in the comparison group), who took part in the Trier Social Stress Test during which their cortisol, heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) reactivity were collected. Results showed that after controlling for age, sex, body mass index, and socioeconomic status, a symmetry between the HPA axis and ANS stress response marked by significantly positive relationships between cortisol reactivity and SBP and DBP reactivity was found in the comparison group, while an asymmetry between the HPA axis and ANS stress response marked by a negative association between cortisol reactivity and DBP reactivity and a null association between cortisol reactivity and SBP reactivity was observed in the child maltreatment group. These findings suggest that child maltreatment disrupts the symmetry between the HPA axis and ANS stress response in adolescents.

Pituitary adenomas are common intracranial neoplasms and represent a clinically relevant but frequently underrecognized cause of secondary osteoporosis and fragility fractures. Hormonal excess, coexisting pituitary deficiencies, and the iatrogenic burden of multimodal treatments act synergistically to impair bone remodeling, microarchitecture, and mechanical strength. Consequently, skeletal fragility may manifest at a relatively young age and is often inadequately predicted by dual-energy X-ray absorptiometry (DXA)-derived areal bone mineral density (aBMD) alone.This narrative review summarizes current evidence on skeletal involvement in functioning pituitary adenomas, including acromegaly, Cushing's disease (CD), prolactinomas, and thyrotropin [TSH]-secreting adenomas (TSHomas), with a specific focus on sex-related differences relevant to clinical practice. Although several pituitary adenomas are more prevalent in women, male patients frequently present with delayed diagnoses, harboring larger and more aggressive tumors. Consequently, men may be affected by a longer cumulative exposure to hormone excess and a higher prevalence and severity of panhypopituitarism, often exacerbated by the mass effect and multiline therapies. Across clinical cohorts, these interacting factors are consistently associated with an increased burden of fragility fractures, particularly in male patients.In pituitary disorders, fracture risk is commonly underestimated because DXA-derived aBMD does not adequately capture alterations in bone quality and structural integrity. Comprehensive skeletal evaluation, including systematic vertebral morphometry, trabecular bone score (TBS), and selected advanced imaging techniques, improves detection of occult fractures and refines fracture risk stratification. Moreover, the persistently low awareness, diagnosis, and treatment rates of osteoporosis in men represent a substantial and potentially modifiable gap in care, particularly in secondary forms related to endocrine diseases.This review highlights the need for a proactive, sex-aware clinical approach that integrates endocrine management with appropriate skeletal assessment and bone-directed therapy, with the aim of reducing fracture burden and improving long-term outcomes in patients with pituitary diseases.

Ertugliflozin is a sodium-glucose co-transporter-2 inhibitor that has demonstrated promise as a treatment for hyperinsulinaemia in horses. Despite the frequent use of ertugliflozin in equine clinical practice, the pharmacokinetics of this drug in horses has not been established. The aim of the present study was to determine the pharmacokinetics of one supratherapeutic dose (0.25 mg/kg) of ertugliflozin in eight horses. Horses were defined as being healthy by physical examination, haematological, blood biochemical and oral sugar test (OST) results. Plasma concentrations of ertugliflozin were quantified using high-performance liquid chromatography-tandem mass spectrometry 0, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 14, 18, 24, 30, 36, 48, 60, 72, 96, and 120 h after drug administration enterally. Non-compartmental analysis led to determination of key pharmacokinetic variables, including mean ± SD time to maximum concentration (Tmax) of 0.91 ± 0.13 h, maximum measured concentration (Cmax) of 267.52 ± 25.37 ng/mL, terminal elimination half-life (T1/2) of 17.65 ± 3.15 h and apparent oral clearance (CL/F) of 106.95 ± 27.53 mL/h/kg. No clinical signs of adverse effects or blood biochemical abnormalities occurred after drug administration. The results of this study suggest that a single supratherapeutic dose of ertugliflozin in healthy horses is safe. The pharmacokinetics of enterally administered ertugliflozin in horses are similar to pharmacokinetics of the drug in humans and the long T1/2 makes ertugliflozin suitable for once daily dosing in horses. It is proposed that a starting dose for ertugliflozin in horses be in the range 0.05-0.1 mg/kg. Further pharmacokinetic studies are required to optimise the dose regimen for treating horses with hyperinsulinaemia.