Anterior Pituitary Research Articles

CD9/SOX2-positive cells in the intermediate lobe of the rat pituitary gland exhibit mesenchymal stem cell characteristics.

Adult tissue stem cells of the anterior pituitary gland, CD9/SOX2-positive cells, are believed to exist in the marginal cell layer (MCL) bordering the residual lumen of the Rathke's pouch. These cells migrate from the intermediate lobe side of the MCL (IL-MCL) to the anterior lobe side of the MCL and may be involved in supplying hormone-producing cells. Previous studies reported that some SOX2-positive cells of the anterior lobe differentiate into skeletal muscle cells. These findings suggest that CD9/SOX2-positive cells in the anterior pituitary have mesenchymal stem cell (MSC) properties. To substantiate this hypothesis, we examined whether CD9-positive cells isolated from IL-MCL of adult male rats differentiate into mesenchymal cells, such as endothelial cells, adipocytes, chondrocytes, and osteocytes. Immunohistochemical analysis revealed that the CD9-positive cells were positive for the MSC markers, CD349, CD105, CD271, and CD273 and were detected in the early postnatal period at the boundary between the posterior and intermediate lobes but not in the embryonic period. In addition, some adult tissue stem cells derived from neural crest cells and bone marrow haematopoietic stem cells were positive for both CD9 and MSC markers, indicating that several CD9/SOX2-positive cells in the IL-MCL of the pituitary gland are MSCs that invaded from external tissues during pituitary development in the early postnatal period and exist in the adult tissue stem cells as suppliers of hormone-producing and endothelial cells in the anterior lobe. These findings should have implications for the application of CD9/SOX2-positive cells in regenerative therapy of the pituitary.

Capillary connections between sensory circumventricular organs and adjacent parenchyma enable local volume transmission.

Among contributors to diffusible signaling are portal systems which join two capillary beds through connecting veins. Portal systems allow diffusible signals to be transported in high concentrations directly from one capillary bed to the other without dilution in the systemic circulation. Two portal systems have been identified in the brain. The first was discovered almost a century ago and connects the median eminence to the anterior pituitary gland. The second was discovered a few years ago and links the suprachiasmatic nucleus to the organum vasculosum of the lamina terminalis, a sensory circumventricular organ (CVO). Sensory CVOs bear neuronal receptors for sensing signals in the fluid milieu. They line the surface of brain ventricles and bear fenestrated capillaries thereby lacking blood-brain barriers. It is not known whether the other sensory CVOs, namely the subfornical organ (SFO), and area postrema (AP) form portal neurovascular connections with nearby parenchymal tissue. To preserve the integrity of the vasculature of CVOs and their adjacent neuropil, we combined iDISCO clearing and light-sheet microscopy to acquire volumetric images of blood vessels and traced the vasculature in two experiments. In the first, the whole brain vasculature was registered to the Allen Brain Atlas in order to identify the nuclei to which the SFO and AP are attached. In the second study, regionally specified immunolabeling was used to identify the attachment sites and vascular connections between the AP, and the SFO to their respective parenchymal attachment sites. There are venous portal pathways linking the capillary vessels of the SFO and the posterior septal nuclei, namely the septofimbrial nucleus and the triangular nucleus of the septum. Unlike the arrangement of portal vessels, the AP and the nucleus of the solitary tract share a common capillary bed. Taken together, the results reveal that all three sensory CVOs bear direct capillary connections to adjacent neuropil, providing a direct route for diffusible signals to travel from their source to their targets.

Anterior pituitary gland volume mediates associations between adrenarche and changes in transdiagnostic symptoms in youth.

The pituitary gland (PG) plays a central role in the production and secretion of pubertal hormones, with documented links to the increase in mental health symptoms during adolescence. Although literature has largely focused on examining whole PG volume, recent findings have demonstrated associations among pubertal hormone levels, including dehydroepiandrosterone (DHEA), PG subregions, and mental health symptoms during adolescence. Despite the anterior PG's role in DHEA production, studies have not yet examined potential links with transdiagnostic symptomology (i.e., dysregulation) pertinent to long-term functioning. Therefore, the current study sought examine whether anterior PG volume mediates associations between DHEA levels and changes in dysregulation symptoms in an adolescent sample (N = 114, 9 -17 years, Mage = 12.87, SD = 1.88). Following manual tracing, structural equation modeling revealed that greater anterior, not posterior, PG volume mediated the association between greater DHEA levels and increasing dysregulation symptoms across time, controlling for baseline dysregulation symptom levels. Results also showed that greater DHEA levels related to decreasing symptoms across time, suggesting potential attenuation effects. Altogether, these results provide support for separating the anterior and posterior PG by demonstrating specificity in the role of the anterior PG in adrenarcheal processes that may confer risk for adolescent psychopathology.

Prolactin-induced sensitization of trigeminal nociceptors promotes migraine co-morbidity in endometriosis

Background Women with endometriosis are more likely to have migraine. The mechanisms underlying this co-morbidity are unknown. Prolactin, a neurohormone secreted and released into circulation from the anterior pituitary, can sensitize sensory neurons from female, but not male, rodents, monkeys and human donors. Methods We used a syngeneic model of endometriosis to determine whether elevated prolactin levels can sensitize trigeminal ganglion neurons and increase vulnerability to migraine pain. Results Mice with endometriotic lesions showed increased serum prolactin levels and developed persistent abdominal, but not cephalic, allodynia. However, inhalation of a transient receptor potential ankyrin 1 agonist, umbellulone, a known environmental trigger of headache in some patients, elicited cephalic allodynia in mice with endometriosis but not sham controls, suggesting that endometriosis can promote sensitization of trigeminal neurons and migraine attacks. Endometriosis dysregulated the expression of prolactin receptor isoforms in trigeminal neurons and increased their excitability measured by in vitro patch clamp electrophysiology. Inhibition of pituitary prolactin following a 2-week treatment with a dopamine receptor agonist, cabergoline, prevented cephalic allodynia elicited by activation of trigeminal afferents with umbellulone. Cabergoline treatment also normalized the expression of prolactin receptor isoforms in trigeminal ganglia and the hyperexcitability of trigeminal neurons. Conclusions These data demonstrate that circulating prolactin in endometriosis promotes vulnerability to migraine through sensitization of trigeminal afferents. Clinically available dopamine receptor agonists or novel monoclonal antibodies targeting prolactin signaling may be effective for migraine prevention in women with endometriosis.

Inflammation of adenohypophysis is commonly associated with headache in surgically managed Rathke's cleft cysts.

Rathke's cleft cysts (RCC) are present in up to 20% of autopsy studies but only a minority necessitate surgical treatment. Inflammation of RCC is thought to be significant in three processes: the development of classical symptoms, a predisposition to rupture or apoplexy, and increasing the rate of RCC recurrence. We aim to characterize clinical presentation, histological and radiological findings in patients with surgically managed RCC. We conducted a retrospective case series of 31 RCC, which had undergone surgical management between April 2016 and April 2024. Histopathology and radiology were independently reviewed by neuropathologist and neuroradiologist, and case notes were reviewed for clinical and biochemical data. Median age was 43 years (IQR 32-63); 77% were female. 23/31 demonstrated inflammation of RCC cyst epithelium (n = 13), cyst wall (n = 20) or anterior pituitary (adenohypophysitis) (n = 12). 8 cases were not inflamed. Preoperative features included pituitary dysfunction (70%), headache (65%), visual disturbance (26%) and polyuria/polydipsia (7%). Six patients presented with features of apoplexy. Headache was more prevalent (92%) in patients with adenohypophysitis vs. those without (47%), p = 0.020, and present in all 11 cases where inflammation in the adenohypophysis was chronic. Pituitary dysfunction was not associated with inflammation overall (76% vs. 70% p = ns), nor specifically within the adenohypophysis (75 vs. 63% p = 0.69). Histological inflammation was associated with radiological loss of posterior bright spot (70% vs. 14% p = 0.024). Headache but not pituitary dysfunction was associated with adenohypophyseal inflammation. A trend of increasing headache prevalence was seen with increasing degree of inflammatory infiltrate within RCC.

Rathke’s cleft cyst: A case report

Abstract A Rathke cleft cyst (RCC) is a nonmalignant growth originating from Rathke’s pouch, which is the precursor to the anterior pituitary gland during early development. Most RCCs are asymptomatic and are typically discovered incidentally during computed tomography scans or magnetic resonance imaging (MRI). The progressive enlargement of the RCC is often symptomatic due to compression of the adjacent structures. The clinical presentations of the RCC are headache, visual disturbances, pituitary dysfunction causing hypogonadism, hyperprolactinemia, deficits of growth hormones, hypothyroidism, and diabetes insipidus. The conventional treatment of the symptomatic RCC is surgical excision through a transsphenoidal approach. Here, we are presenting a patient of Rathke’s cleft cyst presenting severe headache that was relieved after endoscopic transsphenoidal decompression of the cyst.

Identifying Growth Hormone Deficiency in Brain-Injured Patients: The Quality of Life Scale-99.

Traumatic brain injury (TBI) is frequently associated with hypopituitarism. The hypothalamic-pituitary axis appears to be susceptible to the same forces that cause injury to the parenchyma of the brain. Following even a mild TBI (mTBI), patients may suffer transient or permanent decreases in anterior pituitary hormones, including somatotropin (growth hormone [GH]), gonadotropins (luteinizing hormone and follicle-stimulating hormone), thyrotropin, and adrenocorticotropic hormone, with the most frequent long-term deficiency being GH deficiency (GHD). GHD is common after mTBI and is often the cause of persistent post-concussive symptoms a year or more post-injury. GHD is known to cause physical and cognitive fatigue, cognitive inefficiency, metabolic changes, and a range of psychological symptoms. Confusing the picture is that some symptoms of GHD are also common to brain injury itself. To facilitate the detection of GHD when comorbid with TBI, we utilized a new symptom inventory, the Quality-of-Life Scale-99 (QoLS-99), and administered it to a cohort of chronic TBI subjects with and without GHD, distinguished using the insulin tolerance test (ITT). Between 2018 and 2023, 371 patients completed the QoLS-99, of which 263 underwent GH testing with the ITT. Of these 263 patients, 136 (52%) were diagnosed with GHD. A retrospective comparison of QoLS-99 scores found that loss of libido (p < 0.006), a reliance on sleep aids (p < 0.011), and feeling overweight (p < 0.015) were the strongest univariate predictors of GHD. Most survey items did not elicit a significant difference in response between the GHD groups, and for those that did, effect sizes were mild to moderate. Still, initial findings demonstrate strong predictive value in a subset of survey items (i.e., GHD symptoms) that are most discriminating in the sample of patients with TBI. A multivariate prediction model using this subset of questions was able to differentiate GHD status in patients with TBI, correctly identifying 88% of GHD cases with a 37% false positive rate. Based on these findings, we recommend that clinicians inquire about libido, insomnia, and body image as potential markers for GHD. Furthermore, given the amenability of patients with GHD to growth hormone replacement therapy, we strongly encourage clinicians and basic scientists to develop interventions for the large and underserved population of patients with TBI with comorbid GHD.

Investigation the impact of turmeric supplementation on mRNA expression of growth-related peptides and gut health in broilers

Antibiotic resistance has prohibited its use for non-therapeutic purposes in livestock. Recent studies have suggested that turmeric, a natural compound, could serve as a potential alternative to antibiotics in promoting growth in chickens. Therefore, this study aimed to determine the effects of turmeric supplementation on the gene expression of growth-related peptide and mucin2, an indicator of intestinal health, in broilers. We added two percentages of turmeric (0.5% and 1%) to the standard diet, categorizing them as turmeric 0.5% and turmeric 1%, and compared the results with the control group (turmeric 0.0%). Gene expression analysis was conducted anterior pituitary (APit), liver, and intestine. The results showed that body weight gain was higher in the turmeric-treated groups, and feed conversion ratio was improved significantly, indicating that turmeric is more efficient in converting feed into body mass. Analysis of gene expression by RT-qPCR revealed an increase in mucin2 gene expression in the turmeric-treated groups, suggesting an enhancement of gut health. Furthermore, the study found overexpression of the growth hormone (GH) and thyroid-stimulating hormone mRNA expression in the APit. In the liver, an increase in the mRNA expression of the GH receptor in the turmeric-treated groups could facilitate GH action on hepatocytes, leading to an increase in the gene expression of insulin-like growth factors and their binding proteins, which supports muscle cell differentiation and proliferation. Data suggested that turmeric might stimulate myoblast differentiation and satellite cell proliferation to increase muscular growth. In summary, turmeric addition promoted body growth by activating certain genes and inhibiting others. This effect could be due to an increase in the expression of genes that drive muscle cell proliferation. Finally, turmeric enhances gut health through the mucin2 gene.

Research progress on FSH-FSHR signaling in the pathogenesis of non-reproductive diseases.

Follicle-stimulating hormone (FSH), a glycoprotein hormone synthesized and secreted by the anterior pituitary gland, plays a critical role in reproductive development and regulation by binding to FSH receptor (FSHR). Beyond reproductive tissue, FSHRs have been identified in various non-reproductive tissues, indicating broader functions. FSH levels chronically rise during menopause and remain elevated in postmenopausal life. This increase in FSH level has been indicated to be associated with heightened risk of several non-reproductive diseases, including osteoporosis, hypercholesterolemia, type 2 diabetes mellitus, obesity, cardiovascular disease, Alzheimer's disease, and certain cancers. In this review, we will examine the role of FSH-FSHR signaling in the pathogenesis of these non-reproductive diseases and explore therapeutic strategies targeting FSH-FSHR signaling pathways.

Reference intervals for serum prolactin concentrations: analytical and clinical considerations.

Prolactin is a 23kDa protein synthesised and released by lactotrophs located in the anterior pituitary gland. The main function of prolactin is the development of the mammary glands and the production and maintenance of milk secretion during pregnancy and lactation. Prolactin is present in 3 forms in the circulation monomeric, dimeric and macroprolactin which is one of the causes of variability between assay manufacturers. Although most assays have been standardised using the WHO's 3rd international standard there is still considerable variability between commercially available assays and as such laboratories need to establish their own reference intervals. Clinicians use reference intervals to distinguish between healthy and diseased individuals. Direct methods to establish reference intervals are expensive and time consuming and are impractical for most routine clinical laboratories. Indirect methods using the laboratories own data are more commonly used but also have drawbacks. Determination of reference intervals for prolactin is particularly difficult due to various physiological causes for variation in prolactin levels including age, sex and menopause. The presence of macroprolactin, its detection and methods for reporting its presence adds to reference interval determination complexity and harmonisation of these methods may improve clinical care.

Place of surgery in prolactinomas treatment (clinical study)

Relevance. Prolactinoma is one of the most common neuroendocrine tumors of the pituitary. Its prevalence 77,6 per 100,000 patients with pituitary masses. The first line of treatment for prolactinomas is drug therapy with dopamine agonists (DA). Cabergoline is the medicine of choice because it is more effective and has a better safety profile. In approximately 15 % of patients who fail to achieve remission of the disease even on the maximum tolerated dose of cabergoline, they are recommended to undergo transsphenoidal adenomectomy (TSA). However, in real clinical practice, when surgical treatment is performed despite achieving or nor achieving maximum tolerated dose of DA including being considered as first line of treatment. Knowing that risk of complications of TSA at the centers of excellence is practically zero and the development of remission is expected immediately after surgery, the choose of using TSA in the treatment of prolactinomas is being discussed.Purpose and objectives of the study. Using the example of a specialized neurosurgical hospital, study the population of patients operated prolactinomas, determine the reasons for performing TSA, compare the contribution of known factors influencing remission of the disease after surgical treatment, and identify among them the most significant for the study population.Materials and methods. The study included patients with prolactinoma who performed TSA at the V.A. Almazov National Medical Research Center in the period from 01.2018 to 03.2023, and the diagnosis of prolactinoma was confirmed by data from a morphological study of the surgical material (excatly, cells adenoma expressed prolactin). Based on the results of TSA, patients were divided into 2 groups depending on the outcome of the operation: a group of patients with succesful surgery and a group where there was no effect from the TSA (unsuccessful operation). The outcome of the operation was considered succesful when: 1) the fact of normoprolactinemia for 1 year after TSA, 2) to a significant (more than 50 %) reduction in the need for DA.Results. The study included 60 patients with prolactinoma who performed TSA. Among the included patients, there were 36 men (60 %) and 24 women (40 %). The median age at diagnosis was 43 (Q1–Q3: 38–47) years for men and, 52 (Q1–Q3: 41–60) years for women. In 26 (43 %) patients, the indications for surgery corresponded to clinical recommendations: meanwhile 34 patients (56 %) were operated on at the request of the patient/doctor’s choice. Patients didn’t differ in age in the two groups (p = 0.447). Patients in the unsuccessful surgery group received DA therapy for a longer period of time (48 against 9 months, p &lt; 0.001) and their weekly dosage was higher compared to patients with a positive effect from surgery (4 vs. 2 mg/week, p &lt; 0.001). There was a statistically significant difference in such indicators as visual field impairment, deficiency of hormones of the anterior pituitary gland before/after surgery (p &gt; 0.05).Conclusion. In the study population, TSA was successful in 38 of them (63 %). The factors determining TSA success were the value of preoperative prolactin — 2476.5 ng/ml, the degree of invasion into the cavernous sinus according to the Knosp classification, the weekly dosage and duration of DA therapy.

Bilateral Correlational Behavior of Pyroglutamate Aminopeptidase I Activity in Rat Photoneuroendocrine Locations During a Standard 12:12 h Light–Dark Cycle

We previously described the circadian variation and bilateral distribution of pyroglutamate aminopeptidase I (pGluPI) activity levels in photoneuroendocrine locations of adult male rats during a standard 12:12 h light–dark cycle. However, the correlational analysis between such locations has not yet been studied. This may provide new data about the unilateral and bilateral functional interaction between photoneuroendocrine locations under light and dark conditions. We analyzed the correlations between locations of a photoneuroendocrine circuit consisting of retina, anterior hypothalamus, superior cervical ganglion, and pineal gland, as well as other related photoneuroendocrine locations: posterior hypothalamus, anterior pituitary, posterior pituitary, occipital cortex, and serum. In particular, we analyzed the correlations between the left retina or the right retina versus the rest of the locations, as well as the correlations between the left and right sides of paired structures at the different time points selected from 12 h light and 12 h dark periods. Also, the profiles of correlational results were compared with the corresponding mean levels. The results demonstrate the complexity of asymmetrical brain behavior. The correlation profile did not always parallel the profile observed with the mean activity values. The diurnal behavior of correlations with the left or right retina differed from one location to another. Likewise, the diurnal variation of correlations between the left and right sides of the paired structures differed between them. Particularly, while most correlations between the left versus right sides of paired structures showed positive values, that of the posterior hypothalamus showed a negative value at 13 h of light period. In addition, except the posterior hypothalamus, most paired locations only correlated significantly with right retina at 07 h of the light period. The results demonstrate the dynamic complexity of brain asymmetry, which represents a challenge for understanding its functional meaning.

Real-time intraoperative ultrasound imaging of the posterior pituitary gland during endoscopic endonasal approach.

Pituitary adenomas are amongst the most common benign central nervous system tumors, and often require resection via an endoscopic endonasal approach (EEA). Two of the most common associated complications are central diabetes insipidus (DI) and syndrome of inappropriate antidiuretic hormone secretion (SIADH). Both are thought to be caused by manipulation of the posterior pituitary gland (PPG), making intraoperative visualization and preservation of this structure critical. Intraoperative endoscopic endonasal ultrasound (IEUS) may present an optimal tool for this purpose. This study aims to describe the appearance and morphology of the PPG on IEUS. This study included all pituitary adenoma surgeries during which IEUS was utilized and the PPG was visualized between 1/1/2022, and 12/31/2023. Demographic, clinical, pathological, and radiological data were retrospectively collected. The PPG was described as either hypoechoic, isoechoic, or hyperechoic as compared to the anterior pituitary gland and adenoma, and the morphology of the PPG was further classified as ellipse or crescent shaped. The PPG was hypoechoic in all 43 cases included in our final cohort (100.0%). Morphologically, the PPG appeared elliptical in 27 cases (62.8%), and crescent shaped in 16 cases (37.2%). The PPG can typically be visualized by IEUS as a hypoechoic structure immediately anterior to the posterior wall of the sella turcica, with elliptical morphology being the most common appearance. These characteristics can be used by the skull base surgeon to more confidently identify the position and morphology of the PPG intraoperatively for its' preservation.

Polysaccharides from Cordyceps cicadae Ameliorate Reproductive Impairments in Male Mouse through the Hypothalamic-Pituitary-Testicular Axis.

Cordyceps cicadae polysaccharides have received attention due to their potential in treating hyperglycemia and enhancing renal function. The beneficial effect of the purified C. cicadae polysaccharides fraction (CCP-1) on the reproductive impairments and spermatogenesis dysfunction of immunocompromised mice is unavailable and is studied herein. The study establishes a GC-1 spg cell apoptosis model induced by TNF-α+SM-164 (TS) and male mouse reproductive injury model induced by cyclophosphamide (CTX), and then intervened by CCP-1. CCP-1 improves the viability of GC-1 spg cell and inhibits cells apoptosis induced by TS in vitro. CCP-1 enhances sperm quality and spermatogenesis function, as well as ameliorating the histological lesions in the hypothalamus, testicular, and kidney. CCP-1 elevates gonadotropin-releasing hormone (GnRH) level that secreted by the hypothalamus, and increases the levels of follicle stimulating hormone (FSH) and luteizing hormone (LH) in the anterior pituitary stimulated by GnRH, and promotes the secretion of testosterone (T) by testis. Moreover, CCP-1 could protect the reproductive system by activating reproductive regulatory pathway such as SCF/C-kit pathway and inhibiting apoptotic signaling pathway such as Bax/Caspase-3 pathway. These results manifest that CCP-1 could serve as a natural promising reproductive system protective supplement for ameliorating CTX biotoxicity.

TMOD-06. ESTABLISHMENT OF PITUITARY NEUROENDOCRINE TUMOR (PITNET) ORGANOID MODELS

Abstract Pituitary neuroendocrine tumors (PitNETs) are tumors that originate from the anterior pituitary gland. While they are mostly benign, they can cause various clinical symptoms due to hormonal secretion abnormalities. PitNET can be broadly categorized into three lineages, each of which has its differentiation controlled by specific transcription factors. Treatment options for PitNET include surgical resection and pharmacotherapy, but available drugs are limited, and their efficacy markers remain unclear. To develop novel drugs for PitNET and identify their efficacy markers, it is necessary to develop new research models. In recent years, organoid models have garnered attention as novel research models for various cancer types. In this study, we established novel organoid models derived from PitNET patients and analyzed their histological and endocrinological characteristics. Surgical specimens from 4 cases of somatotroph adenoma, 1 case of double adenoma, 1 case of gonadotroph adenoma, and 1 case of corticotroph adenoma were minced in dissection medium and embedded in Matrigel basement membrane matrix respectively. The organoids were cultured under 5% CO2 at 37°C using media supplemented with various growth factors. After 28 days of culture, formalin-fixed paraffin-embedded sections were prepared to examine histological homology with patient tumors. Hematoxylin and eosin staining results showed that all organoids maintained cell morphology and tissue structure similar to the original tumors. Immunohistochemical staining for markers specific to each PitNET revealed similar staining patterns between the organoids and the original tumors. Furthermore, analysis of hormone levels in the culture medium showed that hormone production capabilities, such as growth hormone and follicle stimulating hormone, were maintained even after long-term culture. In this study, we successfully established PitNET organoid models that retain histological and endocrinological characteristics. These models are expected to serve as useful research tools for elucidating the molecular mechanisms of PitNET and developing novel therapies targeting critical molecular abnormalities.

PIT-1/SF-1 co-expression in pituitary neuroendocrine tumors (PitNETs) with comprehensive review of the literature: How should we best characterize these neoplasms?

The nomenclature and classification of neuroendocrine tumors of the anterior pituitary have undergone significant change over the last few years. Despite the updated classification system as devised by the World Health Organization, some tumors do not fit neatly into the currently defined categories. The most common tumor type not defined by the updated guidelines is a pituitary neuroendocrine tumor with co-expression of SF-1 and PIT-1. In this manuscript, we provide our institutional experience with such unusual cases and combine our findings with those in the available literature to provide the largest, most comprehensive dataset regarding clinical and pathologic information for these unique tumors. Based on our findings, we also propose a classification scheme for pituitary neuroendocrine tumors to integrate lineage, hormonal expression, and clinical function as we believe this constellation of information will best help the clinical teams treating these patients.

The goat PRLR gene: mRNA expression, association analysis of InDel variants with body weight and growth traits

Prolactin is a single-chain peptide hormone produced by the anterior pituitary gland and plays an important role in the reproductive development of mammals. Therefore, we investigated the expression of the PRLR gene in various goat tissues during distinct developmental stages, as well as the correlation between the 16 bp InDel and growth traits in goats. The study findings demonstrated a consistent expression and distribution of PRLR in both yearling and adult goat tissues, with the highest levels observed in the testis. Association analysis showed that in the yearling IMWC goat population (n = 463), this 16 bp InDel variation was associated with body weight (P = 0.026), body height (P = 0.005), body length (P = 0.008), heart girth (P = 0.001), chest depth (P = 0.000075), and chest width (P = 0.005); In the adult IMWC goat population (n = 211), the 16 bp InDel variation was associated with body height (P = 0.011), height across the hip (P = 0.0003), chest depth (P = 0.001), and cashmere fineness (P = 0.022); In all IMWC goat populations (n = 674), this 16 bp InDel was related to body weight (P = 0.042), body height (P = 0.001), body length (P = 0.013), heart girth (P = 0.012), height across the hip (P = 0.038), chest depth (P = 0.001), and chest width (P = 0.006). The bioinformatics analysis has revealed that the significant impact of a 16 bp InDel on growth traits in goats may be attributed to its specific binding to the transcription factors AP-2α and Sp1. These findings suggest that this genetic variant plays a crucial role in the growth and development of goats, making it a valuable DNA marker for selecting goats with superior growth traits.

Causal Relationship Between Immune Cells and Hypopituitarism: Bidirectional Mendelian Randomization Study

Hypopituitarism, one or more pituitary hormones inefficiently produced by the anterior pituitary or released from the posterior pituitary to adapt to the needs of the organism. Existing epidemiological data show that immune-mediated diffuse infiltration of the anterior pituitary is important in the development of hypopituitarism. However, the precise connection between immune cells and hypopituitarism remains unclear. This study aimed to elucidate the potential causal links between the 731 immune cell types and hypopituitarism risk. Based on data from a genome-wide association study (GWAS), a bidirectional two-sample Mendelian Randomization (MR) analysis was performed using five methods to explore the potential influence of immune cell phenotypes on hypopituitarism. Sensitivity analyses were conducted to examine the robustness of these findings. Our findings support that B cells, T cells, Tregs, dendritic cells, monocytes, and myeloid cells each have a bidirectional influence on hypopituitarism. One B-cell phenotype was associated with increased hypopituitarism risk, while two B-cell phenotypes play a protective role in hypopituitarism. Moreover, seven T-cell phenotypes demonstrate significant protective properties on hypopituitarism. Seven Tregs were associated with increased hypopituitarism risk. Furthermore, one monocyte was identified to be significantly associated with hypopituitarism risk. In addition, reverse MR analysis revealed that hypopituitarism was positively associated with 30 additional immune cell phenotypes and negatively associated with 17 immune cells. Our investigation shed light on the intricate potential relationship between immune cells and hypopituitarism via genetic methods, underscoring the immune-mediated pathway in hypopituitarism pathogenesis, thereby offering valuable insights for future clinical investigations.

GHRH and the prostate.

In the late 1960s and early 1970s, hypothalamic regulatory hormones were isolated, characterized and sequenced. Later, it was demonstrated hypothalamic and ectopic production of growth hormone-releasing hormone (GHRH) in normal and tumor tissues, of both humans and animals. Pituitary-type GHRH receptors (pGHRH-R) had been demonstrated to be expressed predominantly in the anterior pituitary gland but also found in other somatic cells, and significantly present in various human cancers; in addition, the expression of splice variants (SVs) of GHRH receptor (GHRH-R) has been found not only in the pituitary but in extrapituitary tissues, including human neoplasms. In relation to the prostate, besides the pGHRH-R, it has been detected the presence of truncated splice variants of GHRH-R (SV1-SV4) in normal human prostate and human prostate cancer (PCa) specimens; lastly, a novel SV of GHRH-R has been detected in human PCa. Signaling pathways activated by GHRH include AC/cAMP/PKA, Ras/Raf/ERK, PI3K/Akt/mTOR and JAK2/STAT3, which are involved in processes such as cell survival, proliferation and cytokine secretion. The neuropeptide GHRH can also transactivate the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor (HER)-2. Thus, GHRH-Rs have become drug targets for several types of clinical conditions, including prostate-related conditions such as prostatitis, benign hyperplasia and cancer. Over the last fifty years, the development of GHRH-R receptor antagonists has been unstoppable, improving their potency, stability and affinity for the receptor. The last series of GHRH-R antagonists, AVR, exhibits superior anticancer and anti-inflammatory activities in both in vivo and in vitro assays.

Subacute Toxicity Study of Alchornea cordifolia Ethanolic Leaf Extract on the Pituitary Gland of Wistar Rats

Introduction: Herbal medicines are plant-based products used to treat various illnesses and their uses have dramatically increased over the past years in many developed and developing nations. Alchornea cordifolia is one of these plants with reports of its use in health promotion. Some plants exhibit toxicity due to the presence of phytochemicals inherent in them, therefore further studies are necessary in evaluating their toxicity levels. In this study, the sub-acute toxicity of ethanolic extract of Alchornea cordifolia leaves was investigated on the pituitary gland of adult male Wistar rats. The objective was to determine its effect on the histology of the anterior pituitary gland. Methods: Twenty (20) adult male Wistar rats weighing 140-200 were used for the research and were randomly divided into four groups labelled A, B, C. and D. Each group consisted of five (5) rats. Group A (normal control) received normal saline, while group B, C and D received 500 mg/kg, 1,000 mg/kg and 1,500 mg/kg body weight of Alchornea cordifolia extract respectively with the aid of an oral gavage. This was done for a duration of 28 days after which the rats were sacrificed and the pituitary gland obtained for histological analysis using H&amp;E and PAS Orange G staining methods. Results: Histological observations showed that the various doses of the extract used had no detrimental effect of the anterior pituitary gland microstructure in groups B, C, and D when compared to group A. Conclusion: The findings showed that the various doses of Alchornea cordifolia leaf extract used in this study are non-toxic to the anterior pituitary gland in Wistar rats.