Hypophyseal Hormones Research Articles

Clinical and genetic spectrum from a prototype of ciliopathy: Joubert syndrome

ObjectiveJoubert syndrome is a neurodevelopmental disorder with a distinctive hindbrain malformation called molar tooth sign, causing motor and cognitive impairments. More than 40 genes have been associated with Joubert syndrome. We aim to describe a group of Joubert syndrome patients clinically and genetically emphasizing organ involvement. MethodsWe retrospectively collected clinical information and molecular diagnosis data of 22 patients with Joubert syndrome from multiple facilities. Clinical exome or whole-exome sequencing were performed to identify causal variations in genes. ResultsThe most common variants were in the CPLANE1, CEP290, and TMEM67 genes, and other causative genes were AHI1, ARMC9, CEP41, CSPP1, HYLS1, KATNIP, KIAA0586, KIF7, RPGRIP1L, including some previously unreported variants in these genes. Multi-systemic organ involvement was observed in nine (40%) patients, with the eye being the most common, including Leber’s congenital amaurosis, ptosis, and optic nerve coloboma. Portal hypertension and esophageal varices as liver and polycystic kidney disease and nephronophthisis as kidney involvement was encountered in our patients. The HYLS1 gene, which commonly causes hydrolethalus syndrome 1, was also associated with Joubert syndrome in one of our patients. A mild phenotype with hypophyseal hormone deficiencies without the classical molar tooth sign was observed with compound heterozygous and likely pathogenic variants not reported before in the KATNIP gene. ConclusionSome rare variants that display prominent genetic heterogeneity with variable severity are first reported in our patients. In our study of 22 Joubert syndrome patients, CPLANE1 is the most affected gene, and Joubert syndrome as a ciliopathy is possible without a classical molar tooth sign, like in the KATNIP gene-affected patients.

Extended endoscopic endonasal approach for resecting anterior intrinsic third ventricular craniopharyngioma.

BackgroundThe surgical treatment of the extended endoscopic endonasal approach (EEEA) is a safe and effective treatment for suprasellar craniopharyngiomas. However, due to damage to the hypothalamus and third ventricle floor (TVF), EEEA is generally regarded as unsuitable in treating intrinsic third ventricle craniopharyngioma (ITVC) that is entirely within the third ventricle. Until now, there have been only a small number of reports using EEEA to treat TVC via a supra-infrachiasmatic approach. Given that the translamina terminalis (TLT) corridor was used in the transcranial subfrontal approach, EEEA via a suprachiasmatic approach may be feasible and practical to treat ITVC. In the current study, we accumulated experience applying the suprachiasmatic translamina terminalis (STLT) corridor for anterior treatment of ITVC.MethodsFrom March 2016 to December 2020, 14 patients with ITVC in our center were analyzed retrospectively. All patients underwent surgery by EEEA via an STLT corridor. The multilayer reconstruction technique was adopted to achieve skull base reconstruction. Data concerning the patient’s tumor resection, vision, hypophyseal hormone, and complications were collected.ResultsGross-total resection was achieved in 13 (92.8%) of14 patients, with achievement of near-total (90%) resection in the remaining 1 patient. Nine cases (64.3%) were papillary craniopharyngiomas, and the other 5 cases were adamantinomatous subtypes. Postoperatively, 3 patients with pituitary insufficiency received hormone replacement therapy. No permanent diabetes insipidus or hypothalamic obesity was found. All pairs showed significant improvement or stability in vision except 1 patient who encountered visual deterioration. No other neurological deficit occurred postoperatively. Observation results for the exudation of nasal tissue and the length of hospitalization were satisfactory. After a mean follow-up period of 26.2 months, tumor recurrence was not observed.ConclusionTLT is a minimally invasive corridor used in EEEA for treating anterior ITVC without increasing risks of visual and hormonal deficits. The multilayered reconstruction technique we used is a safe and effective method for achieving watertight closure and avoiding cerebrospinal fluid leaks and infection. The endonasal approach via STLT provides a new, safe and efficacious operative strategy that should be considered a surgical alternative in treating ITVC.

Hypophysial angiogenesis decodes annual time and underlies physiological adaptation to seasonal changes in the environment.

Adaptation to annual changes in the environment is controlled by hypophysial hormones. In temperate zones, photoperiod is the primary external cue that regulates annual biological cycles and is translated by the pattern of melatonin secretion acting primarily in the hypophysial pars tuberalis. Angiogenic mechanisms within this tissue contribute to decode the melatonin signal through alternative splicing of the vascular endothelial growth factor A (VEGF-A) gene in both the pars tuberalis and the capillary loops of the infundibulum. The resulting melatonin-evoked differential productions of VEGF-A isoforms will induce seasonal remodeling of the vascular connection between the hypothalamus and hypophysis, and act as paracrine messengers in the pars distalis to generate the required seasonal endocrine response. Specifically, the long melatonin signal in winter upregulates antiangiogenic VEGF-A isoforms, which will reduce the number of vascular loops and the density of VEGF receptors in endocrine and folliculo-stellate (FS) cells, inhibit prolactin secretion, and stimulate FSH. In contrast, the short melatonin signal in summer upregulates proangiogenic VEGF-A isoforms that will increase the number of vascular loops and the density of VEGF receptors in endocrine and FS cells, stimulate prolactin secretion, and suppress FSH. A similar system has been identified in long day seasonal breeders, revealing that this is a conserved mechanism of adaptation across species. Thus, an angiogenesis-based, intrahypophysial system for annual time measurement controls local microvascular plasticity and conveys the photoperiodic signal readout from the melatonin sensitive pars tuberalis to the endocrine cells of the pars distalis to regulate seasonal adaptation to the environment.

Analysis of perioperative negative emotion risk factors in patients with pituitary adenoma and its impact on prognosis: a retrospective study.

BackgroundPituitary adenoma (PA) is the third most common tumor in craniocerebral surgery. Most patients will experience varying degrees of negative emotions before and after surgery, which may affect the prognosis of surgery. This study analyzed the perioperative negative emotional risk factors of patients with different characteristics of PA and their impact on prognosis, so as to provide a reference for improving the prognosis of patients with PA.MethodsA total of 234 patients who underwent PA surgery in the Affiliated Hospital of Nantong University from January 2017 to January 2022 were selected as the observation population. The general characteristics of the subjects were collated using a general information questionnaire designed by the researchers. The negative emotions of the patients were evaluated using a Self-rating Anxiety Scale (SAS) and a Self-rating Depression Scale (SDS). The prognosis of patients was determined by assessing the hypophyseal hormone levels. Multiple regression analysis and logistic regression were used to analyze the risk factors of perioperative negative emotions and the effects of negative emotions on patient prognosis.ResultsMultiple regression analysis showed that with and without children, education, income, PA type, PA size, and surgical approach were independent factors influencing negative emotions in patients after PA surgery (P<0.05). Logistic regression analysis showed that negative emotion was an independent prognostic factor (P<0.05).ConclusionsThere are many factors that affect the anxiety and depression of patients after PA surgery. The family members and medical staff of the patients should take effective measures to relieve the anxiety and depression of the patients so as to improve the prognosis of patients according to the influencing factors.

Endogenous and Synthetic Regulators of the Peripheral Components of the Hypothalamo-Hypophyseal-Gonadal and -Thyroid Axes

Activity in the peripheral components of the hypothalamo-hypophyseal-gonadal and -thyroid axes is regulated by hypophyseal hormones – gonadotropins and thyrotropic hormones (thyroid-stimulating hormone, TSH), which are secreted by specialized cells in the adenohypophysis. Luteinizing hormone (LH) and its homolog chorionic gonadotropin (CG) realize their steroidal effects by binding to LH/CG receptors on the surfaces of Leydig cells in the testes and theca cells and granulosa cells in mature follicles in the ovaries. Follicle-stimulating hormone (FSH) binds FSH receptors on Sertoli cells in the testes and granulosa cells in primordial and maturing follicles in the ovaries, controlling the processes of folliculogenesis, spermatogenesis, and steroidogenesis. TSH, via activation of TSH receptors, stimulates the synthesis of thyroid hormones by thyrocytes in the thyroid gland. Gonadotropins (LH, CG, and FSH) and TSH, which bind with high affinity to the extracellular domains of specific G protein-coupled receptors, directly activate various signal cascades operating via different types of G-proteins and β-arrestins. Recombinant gonadotropins and gonadotropins extracted from natural sources and used for the treatment of reproductive dysfunction and as assisted reproduction technologies have a number of drawbacks, which has led to the development of peptide and low molecular weight regulators of LH/CG and FSH receptors which interact with allosteric sites on the transmembrane or cytoplasmic domains of the receptors. Wide perspectives in the regulation of reproductive functions and the control of fertility are opened up by the use of adipokines, peptides of the insulin and relaxin families, and the antidiabetic drug metformin, which not only regulate and modify the responses of the gonads to gonadotropins, but also themselves influence steroidogenesis and gamete maturation. In the case of TSH receptors, the most acute problem is that of reversing increases in their activity in autoimmune and oncological diseases of the thyroid gland and in endocrine ophthalmopathy. The greatest potential in this direction lies in the ongoing development of low molecular weight inverse agonists and neutral antagonists, which interact with an allosteric site located in the transmembrane domain of the TSH receptor. The present review addresses contemporary advances in the development and study of endogenous and synthetic regulators and modulators of gonadotrophic and TSH receptors, along with their influences on the peripheral components of the hypothalamo-hypophyseal-gonadal and -thyroid axes.

Proposal of a clinically relevant working classification of pituitary neuroendocrine tumors based on pituitary transcription factors

The immunohistochemistry (IHC) characterization of pituitary transcription factors (PTFs) PIT1, TPIT, and SF1, which enable the identification of three different adenohypophyseal cell lines, has been incorporated into the latest classification system of the World Health Organization (WHO) for pituitary adenomas. This change overturns the concept of the adenoma as solely a hormone producer and classifies these tumors based on their cell lineage. The aim of the study was to provide a diagnostic algorithm, based on IHC expression of hypophyseal hormones with potential use in diagnostic practice, contributing to an improved classification of pituitary adenomas. Our sample included 146 pituitary adenomas previously classified based on hormonal subtypes by IHC (former 2004 WHO criteria) and re-evaluated after the IHC quantification of PIT1, TPIT, and SF1 expression, under WHO 2017 recommendations. We assessed the correlation between expression of PTFs and the classification as per hormonal IHCand correlated clinicopathological profiles based on PTFs. The IHC study of PTFs allowed reclassification of 82% of tumors that were negative for all pituitary hormones, with 21 positive cases for SF1 (reclassified as gonadotroph tumors), 1 positive case for TPIT (reclassified as a corticotroph tumor), and 4 positive cases for PIT1. Using SF1 enabled detection of a substantial portion of gonadotroph tumors, reducing the estimated prevalence of null cell tumors to less than 5%, and identification of plurihormonal pituitary neuroendocrine tumors with PIT1-SF1 coexpression and hormone-negative PIT1s, a group in which we did not observe differences in the clinical behavior compared with the rest of the tumors of the same cell lineage.Our results suggest that applying a diagnostic algorithm based on the study of PTFs could contribute to improving the classification of pituitary adenomas. By adding TPIT assessment, we propose a two-step algorithm, with hypophyseal hormones being used in a selective modality, depending on initial results.

Unilateral section of the superior ovarian nerve induces first ovulation in the Zucker fatty (fa/fa) rat

Hyperactivity in the sympathetic nervous system has been shown to be related to the development of ovarian pathologies. In addition, obesity has been found to be associated with multiple reproductive anomalies and is considered a chronic stress condition of low intensity with changes in the peripheral sympathetic activity. Therefore, in the present study, we aimed to evaluate if the information reaching the ovaries through the superior ovarian nerve (SON) modifies the ovarian function of Zucker fatty rats. We performed a unilateral section of the SON at 32 days of age and autopsies were carried out on the day of the first vaginal estrus. The results showed that fatty animals do not ovulate on the day of the first vaginal estrus and exhibit an increase in catecholaminergic fibers and the presence of precystic structures in the ovaries, without changes in the onset of puberty or in the secretion of ovarian and hypophyseal hormones. We also found that the section of the right SON resulted in ovulation on the day of the first vaginal estrus, which was accompanied by a decrease in ovarian noradrenaline content. The section of the left SON caused a delay in puberty without changes in the rest of the parameters. These results provide functional evidence that the peripheral sympathetic innervation participates in the regulation of ovarian functions in an animal model of genetic obesity.

Diabetes insipidus after suprasellar tumor surgery: case report

Introduction: Diabetes insipidus (DI) is a rare water and electrolyte imbalance with hypovolemic hypernatremia characteristic (1:25.000) however can be potentially fatal if not well-anticipated and managed adequately. Brain tumors, either operated or not, may lead to DI (25%). Based on anatomical location, the suprasellar tumor may cause hypophyseal hormone dysfunction. Sellar region tumors can be classified into hypophyseal (90%) and non-hypophyseal (10%). Non-hypophyseal tumors with neurological deficits are more often causing hypophyseal hormone hyposecretion including DI. Sellar tubercle meningioma is one of the sellar region non-hypophyseal tumors which is often encountered and surgically managed. Worsening symptoms may become the surgical indication e.g. headache and visual disturbance. Case: We are reporting two meningioma cases in Salatiga local hospital with almost similar tumor characteristics either size and frontal lobe location. Both cases were managed by similar transcranial tumor excision craniotomy. Their differences were in the presence of neurological manifestations and the degree of hypothalamic compression. One patient developed postoperative DI without thirst thus the clinical manifestation was polyuria which was closely monitored in the intensive ward. We were convinced that the DI incidence was affected by the tumor manifestation and location which can be assessed by computed tomography (CT) scans. Conclusion: The clinicians should anticipate the possibility of post craniotomy DI thus may provide adequate monitoring and management in patients developing postoperative DI.

The Interplay Between Pituitary Health and Diabetes Mellitus - The Need for 'Hypophyseo-Vigilance'.

The anterior and posterior hypophyseal hormones alter glucose metabolism in health and disease. Secondary diabetes may occur due to hypersecretion of anterior pituitary hormones like adrenocorticotrophic hormone in Cushing's disease and growth hormone in acromegaly. Other hormones like prolactin, gonadotropins, oxytocin and vasopressin, though not overtly associated with causation of diabetes, have important physiological role in maintaining glucose homeostasis. Hypoglycaemia is not an unusual occurrence in hypopituitarism. Many of the medications that are used for treatment of hypophyseal diseases alter glucose metabolism. Agents like pasireotide should be used with caution in the setting of diabetes, whereas pegvisomant should be given preference. Diabetes mellitus itself, on the other hand, can alter the functioning of hypothalamic pituitary axis; this is documented in both type 1 and type 2 diabetes. This review focuses on the clinically relevant interplay of hypophyseal hormones and glucose homeostasis. The authors define 'hypophyseo-vigilance' as an approach which keeps the bidirectional, multifaceted interactions between the pituitary and glucose metabolism in mind while managing diabetes and pituitary disease.

Association between Biomarkers of Low-grade Inflammation and Sex Hormones in Women with Polycystic Ovary Syndrome.

Women with polycystic ovary syndrome (PCOS) have higher circulating levels of C-reactive protein, but the relationship between inflammation and endocrine function in PCOS remains poorly understood. Thus, this study aimed to investigate the association between low-grade inflammation and sex hormones in women with PCOS. A comprehensive panel of biomarkers of inflammation was measured in serum of 63 women with PCOS using proximity extension assay technology. Associations of 65 biomarkers with sex hormones were assessed without and with adjustment for age and body mass index (BMI). In the unadjusted analysis, 20 biomarkers were positively correlated with 17-OH-progesterone (17-OH-P), 14 with prolactin and 6 with free testosterone, whereas inverse associations were found for 16 biomarkers with sex hormone-binding globulin (SHBG), 6 with luteinizing hormone (LH) and 6 with estrogen (all p<0.05). Among the positive associations, correlations were mainly found for five chemokines (CXCL11, CCL4, MCP-4/CCL13, CXCL5, CXCL6) and for VEGF-A, LAP-TGFβ1, TNFSF14 and MMP-1. Inverse associations with sex hormones were mainly present for two chemokines (CXCL1, MCP-2/CCL8), CDCP1, CST5 and CSF-1. Adjustment for age and BMI reduced the number of biomarker associations for SHBG and estrogen, but had hardly any impact on associations with 17-OH-P, prolactin, free testosterone and LH. Women with PCOS feature BMI-independent associations between biomarkers of inflammation and certain sex steroid and hypophyseal hormones. Most of these inflammation-related biomarkers were chemokines, which may be relevant as potential mediators of the increased cardiometabolic risk of women with PCOS.

Neonatal Hypopituitarism: Approaches to Diagnosis and Treatment

Hypopituitarism is defined as a decreased release of hypophyseal hormones, which may be caused by disease of the pituitary gland disease or hypothalamus. The clinical findings of neonatal hypopituitarism depend on the causes and on presence and extent of hormonal deficiency. Patients may be asymptomatic or may demonstrate non-specific symptoms, but may still be at risk for development of pituitary hormone deficiency over time. Patient history, physical examination, endocrinological, radiological and genetic evaluations are all important for early diagnosis and treatment. The aim of this paper was to present a review of etiological factors, clinical findings, diagnosis and treatment approaches in neonatal hypopituitarism.

Effect of melatonin on regulation of apoptosis and steroidogenesis in cultured buffalo granulosa cells.

This study was aimed to address melatonin receptor expression, mRNA level of hypothalamus and hypophysis hormone receptors (GnRHR, FSHR, and LHR), steroidogenesis, cell cycle, apoptosis, and their regulatory factors after addition of melatonin for 24hr in cultured buffalo granulosa cells (GCs). The results revealed that direct addition of different concentrations of melatonin (100pM, 1nM, and 100nM) resulted in significant upregulation (p<0.05) of mRNA level of melatonin receptor 1a (MT1) without affecting melatonin receptor 1b (MT2). Melatonin treatment significantly downregulated (p<0.05) mRNA level of FSH and GnRH receptors, whereas 100nM dose of melatonin significantly increased mRNA level of LH receptor. Treatment with 100nM of melatonin significantly decreased the basal progesterone production with significant decrease (p<0.05) in mRNA levels of StAR and p450ssc, and lower mRNA level of genes (Insig1, Lipe, and Scrab1) that affect cholesterol availability. Melatonin supplementation suppressed apoptosis (100nM, p<0.05) and enhanced G2/M phase (1nM, 100nM, p<0.05) of cell cycle progression which was further corroborated by decrease in protein expression of caspase-3, p21, and p27 and increase in bcl2. Our results demonstrate that melatonin regulates gonadotrophin receptors and ovarian steroidogenesis through MT1. Furthermore, the notion of its incorporation in apoptosis and proliferation of buffalo GCs extends its role in buffalo ovaries.

Relation of Anthropometric and Lifestyle Related Factors with Primary Dysmenorrhea

Menstrual cycle is a cycle of natural changes that occurs in the uterus and ovaries as an essential part of making sexual reproduction possible. The biological activity of the menstrual cycle is created by coordination among hypothalamic, hypophyseal and ovarian hormones. Many females suffer from dysmenorrhea, painful cramping sensation in the lower abdomen during menstruation. It is one of the most frequently encountered gynaecological disorders, often accompanied by other biologic symptoms, including fatigue, dizziness, sweating, headaches, back ache, nausea, vomiting, and diarrhoea, all occurring just before or during menses

Prognosis of Hormonal Deficits in Empty Sella Syndrome Using Neuroimaging.

Aim:We have evaluated the anatomic measurements on sellar area of patients who were radiologically diagnosed with empty sella to determine the relation between the amount of pressure on the adenohypophysis and hormonal imbalances.Materials and Methods:Sixty-one cases were diagnosed with empty sella and had hormone tests and hypophysis magnetic resonance (MR). The cases were categorized into two groups – patients with hypophyseal hormone anomaly and patients without hormone anomaly. We have measured interclinoid distance, anteroposterior distance from the anterior diaphragm sella to the pituitary stalk, depth of the sella turcica, craniocaudal distance of the optic chiasm from the diaphragm sella, the heights of the right and left adenohypophysis, subcutaneous fat thickness measured orthogonal to the coronal suture and posteriorly at the level of C2–C3 for two groups on hypophysis and cranial MR imaging MRI.Results:Twenty-five hormone-positive cases (40.9%) (hormone test were abnormal) and 36 hormone-negative cases (59.1%) (hormone tests were normal) were included in the study. The most common hormone abnormality was thyroid-stimulating hormone, T3 and T4 deficiency in 12 cases (48%) and increase in prolactin level in 7 cases (28%). Right adenohypophysis height was 1.54 ± 0.840 mm for the 1st group, and 1.96 ± 0.83 mm for the 2nd group. The left adenohypophysis height was 1.66 ± 0.80 mm for the 1st group, and 1.94 ± 0.94 mm for the 2nd group. It was found out that the thickness at right and left side in the hormone-positive group diminished significantly.Conclusion:Adenohypophysis height and distance between stalk and optic nerve were good determiner for hormone defect.

Serotonin transporter (5‐HTTLPR) genotypes and trinucleotide repeats of androgen receptor exert a combinatorial effect on hormonal milieu in patients with lifelong premature ejaculation

Premature ejaculation is one of the most common sexual disorders in men due to uncontrolled modulation of spinal reflexes controlled by cortico-limbic centers in the brain. In this study, we investigate the combinatorial effects of trinucleotide repeats of androgen receptor and allelic variants of the 5-HTTLPR gene on sex steroids, hypophyseal hormones, sexual performance, and premature ejaculation assessment parameters among evidence-based lifelong premature ejaculation subjects. A total of 271 outpatients (age 26.6±1.9) consulting for evidence-based lifelong premature ejaculatory dysfunction were selected in this study. The control group consists of 155 men with normal IELT (>4min). The study revealed that the subjects who have the highest (≥26) CAG stretches depicted a significantly higher serum oxytocin levels (102.1pg/ml; n=126, p<0.001) compared with the control group (71.2 pg/ml; n = 75, p = <0.001) and patients which have medium (22-25) and short (≤21) CAG stretches (76.63ng/ml; n=64, p<0.001 vs. 77.4ng/ml; n=81, p<0.001). Almost 33 (26.1%) lifelong premature ejaculatory patients had AR variant of longer (≥26) CAG repeats was homozygous for S alleles (SS), 45 (35.7%) was homozygous for L allele (LL), and 48 (38%) had the L/S or S/L genotype of 5-HTTLPR gene. Homozygous (SS) alleles have a significant positive correlation (r=0.44, p<0.0001) with the high score of BDI-II (39.1, n=126, p<0.001). However, LL alleles have shown a significant positive correlation with PEDT (r=0.46, p<0.001) and negative correlation with self-estimated IELT and intercourse satisfaction (r=-0.35, p<0.001). The innovative study design elaborates that androgen receptor trinucleotide repeats and 5-HTTLPR genotypes have combinatorial impact on hormonal milieu and sexual function regarding evidence-based lifelong premature ejaculatory dysfunction patients.

Epilepsy onset in puberty

Objective: To research age of epilepsy onset in puberty in girls. Methods: Research was a part of prospective observational uncontrolled comparative study of the antiepileptic drugs reproductive side effects. The age of epilepsy onset were studied in 155 female patients in reproductive age. 3 groups of puberty age and 4 subgroups of puberty period were allocated. STATISTICA for Windows system (version 5.5) was used. Results: Patients were divided into three groups according WHO classification of puberty age (1997): 1gr. – before puberty- 1–9y.o., 2gr. – puberty- 10–18, 3g. – after puberty- older 18. There were 23 patients (15%) in 1 gr., 92 (59%) – in 2gr, 40 (26%) – in 3 gr. Differences in the epilepsy onset in the comparison groups were statistically significant above in puberty (p<0,001). Epilepsy began in childhood (until 18 y.o) in 75%. Frequency of epilepsy onset was studied in 4 subgroups of puberty period according phases of maturing of hypothalamo-hypophysial system: 10–11y.o- beginning of hypothalamo- hypophysial hormones secretion , 12-13 – beginning menses, 14-15- becoming of ovulatory peak, 17-18- establishment of a constant rhythm of hormones secretion. There were 18 patients (20%) into 1subgr., 35 (38%) – 2nd, 24 (26%)- 3d, 15 (16%) into 4 subgroup. Prevalence of epilepsy onset in the integrated age range of 12-16 years was statistically reliable (p<0,001). Conclusion: Thus, hormonal changes during the puberty period often provoked epilepsy onset. The epilepsy onset prevailed during the periods of the beginning oestradiolum production and its ovulatory peaks. It has confirmed estrogens proconvulsive effect. The reported study was funded by Russian humanitarian scientific fund according to the research project № 15-06-10816.

Evaluation of the Relationship of Intracranial Pressure with the Levels of Hypothalamic-Pituitary-Gonadal Axis Hormones on Prognosis in Severe Brain Injury

Objective: Head traumas have an important place among all traumatic injuries and it is an important public health problem worldwide. Novel methods predicting prognosis may contribute to a decrease in the mortality and morbidity rates. Materials and Methods: Continuous intracranial pressure (ICP) measurements, initial cerebral computed tomography (CT) and measurement of the hypothalamic-pituitary-gonadal (HPG) axis hormones between the 0th and 4th days were performed in 15 adult male patients with severe head trauma. The relationship of these parameters with the short-term results of the patients on the 15th day was evaluated. Additionally, provocation tests were carried out to evaluate the HPG axis function. Results: High ICP and compression of basal cisterna increased mortality and they were found to affect prognosis (p=0.009 and p=0.033, respectively) No statistically significant association was found between midline shift and prognosis. No relationship was found between mortality and mean basal hormone values on the 0th day and between the 1st and 4th days. Conclusion: ICP measurement values and the presence of compression of basal cistern on the initial brain CT can be used to predict the prognosis in severe head injury but there is no significant relationship between hypophyseal hormone values and prognosis.

Intracranial Lesions in Children and Adolescents with Morbid Obesity.

Background:Intracranial lesions may affect the hypothalamo-hypophyseal axis and lead to some neuro-endocrinological dysfunctions (hyperphagia, sleep disorders and hormonal dysfunctions). There is a very limited number of studies about childhood obesity and intracranial lesions.Aims:To evaluate the incidence of intracranial lesions and its role in clinical symptoms and aetiology in cases with morbid obesity who have been admitted to the paediatric endocrinology department with this complaint.Study Design:Cross-sectional study.Methods:A total of 120 cases admitted to the paediatric endocrinology department with the complaint of morbid obesity between 2002 and 2015 were included in this study. A detailed history was taken and a physical examination was performed; biochemical, hormonal parameters were evaluated. Contrast dynamic magnetic resonance imaging was performed in order to visualize cranial pathologies.Results:An intracranial lesions was detected in 16.6% of the patients and 55% of these lesions were adenoma of the hypophysis. Prolactin levels were increased in six patients but front hypophyseal hormone levels were within normal range in the rest of the patients. Growth velocity of the patients was not affected.Conclusion:In our study, the incidence of intracranial lesions in children and adolescents with morbid obesity was much higher than in the normal population. According to this data, we are of the opinion that contrast dynamic magnetic resonance imaging is helpful in children with morbid obesity for the early detection of the mass before it causes any clinical or neurological symptoms and in the prevention of future complications.

Approaches Mediating Oxytocin Regulation of the Immune System.

The hypothalamic neuroendocrine system is mainly composed of the neural structures regulating hormone secretion from the pituitary gland and has been considered as the higher regulatory center of the immune system. Recently, the hypothalamo-neurohypophysial system (HNS) emerged as an important component of neuroendocrine–immune network, wherein the oxytocin (OT)-secreting system (OSS) plays an essential role. The OSS, consisting of OT neurons in the supraoptic nucleus, paraventricular nucleus, their several accessory nuclei and associated structures, can integrate neural, endocrine, metabolic, and immune information and plays a pivotal role in the development and functions of the immune system. The OSS can promote the development of thymus and bone marrow, perform immune surveillance, strengthen immune defense, and maintain immune homeostasis. Correspondingly, OT can inhibit inflammation, exert antibiotic-like effect, promote wound healing and regeneration, and suppress stress-associated immune disorders. In this process, the OSS can release OT to act on immune system directly by activating OT receptors or through modulating activities of other hypothalamic–pituitary–immune axes and autonomic nervous system indirectly. However, our understandings of the role of the OSS in neuroendocrine regulation of immune system are largely incomplete, particularly its relationship with other hypothalamic–pituitary–immune axes and the vasopressin-secreting system that coexists with the OSS in the HNS. In addition, it remains unclear about the relationship between the OSS and peripherally produced OT in immune regulation, particularly intrathymic OT that is known to elicit central immunological self-tolerance of T-cells to hypophysial hormones. In this work, we provide a brief review of current knowledge of the features of OSS regulation of the immune system and of potential approaches that mediate OSS coordination of the activities of entire neuroendocrine–immune network.

Current knowledge of ghrelin in amphibians.

We are exploring physiological importance of the ghrelin system in vertebrates. This review summarizes current knowledge of the ghrelin system in amphibians. Our study on ghrelin precursor in various amphibians revealed that the third amino acid with acyl modification has changed to threonine (Thr-3) instead of serine (Ser-3) only in the genus, Rana. Functional analyses of the ghrelin receptor in three species of amphibians, Japanese fire belly newt, American bullfrog and Japanese tree frog revealed that ghrelin and GHS-R1a agonists increase intracellular Ca2+ concentration in HEK293 cells expressing each receptor, and that ligand selectivity of ghrelin with Ser-3 and Thr-3 that expected to see in the bullfrog receptor was not found in the two frog receptors, but in the newt receptor. The brain, gastrointestinal tract, kidney and gonad highly express GHS-R1a mRNA. In frogs and newt, fasting did not increase GHS-R1a mRNA expression in the brain, but in the stomach. However, intraperitoneal (IP) injection of ghrelin did not affect food intake. A dehydration treatment increased GHS-R1a mRNA expression in the brain, stomach and ventral skin in the tree frog. However, intracerebroventricular (ICV) injection of ghrelin did not affect water absorption. Ghrelin did not influence gastrointestinal motility in in vitro studies using smooth muscle strips of the bullfrog and newt in vitro. These results suggest that the ghrelin system is present in various amphibians, but little is known about the physiological functions except hypophyseal hormone secretion.