Research progress in the treatment of chronic fatigue syndrome through interventions targeting the hypothalamus-pituitary-adrenal axis.

Chronic fatigue syndrome (CFS) causes great harm to individuals and society. Elucidating the pathogenesis of CFS and developing safe and effective treatments are urgently needed. This paper reviews the functional changes in the hypothalamus-pituitary-adrenal (HPA) axis in patients with CFS and the associated neuroendocrine mechanisms. Despite some controversy, the current mainstream research evidence indicates that CFS patients have mild hypocortisolism, weakened daily variation in cortisol, a weakened response to the HPA axis, and an increase in negative feedback of the HPA axis. The relationship between dysfunction of the HPA axis and the typical symptoms of CFS are discussed, and the current treatment methods are reviewed.

Effect of Caffeine on the Inflammatory-Dependent Changes in the GnRH/LH Secretion in a Female Sheep Model.

Caffeine is one of the most widely consumed psychoactive drugs in the world. It easily crosses the blood-brain barrier, and caffeine-interacting adenosine and ryanodine receptors are distributed in various areas of the brain, including the hypothalamus and pituitary. Caffeine intake may have an impact on reproductive and immune function. Therefore, in the present study performed on the ewe model, we decided to investigate the effect of peripheral administration of caffeine (30 mg/kg) on the secretory activity of the hypothalamic-pituitary unit which regulates the reproductive function in females during both a physiological state and an immune/inflammatory challenge induced by lipopolysaccharide (LPS; 400 ng/kg) injection. It was found that caffeine stimulated (p < 0.01) the biosynthesis of gonadotropin-releasing hormone (GnRH) in the hypothalamus of ewe under both physiological and inflammatory conditions. Caffeine also increased (p < 0.05) luteinizing hormone (LH) secretion in ewes in a physiological state; however, a single administration of caffeine failed to completely release the LH secretion from the inhibitory influence of inflammation. This could result from the decreased expression of GnRHR in the pituitary and it may also be associated with the changes in the concentration of neurotransmitters in the median eminence (ME) where GnRH neuron terminals are located. Caffeine and LPS increased (p < 0.05) dopamine in the ME which may explain the inhibition of GnRH release. Caffeine treatment also increased (p < 0.01) cortisol release, and this stimulatory effect was particularly evident in sheep under immunological stress. Our studies suggest that caffeine affects the secretory activity of the hypothalamic-pituitary unit, although its effect appears to be partially dependent on the animal's immune status.

Dissociating Mechanisms That Underlie Seasonal and Developmental Programs for the Neuroendocrine Control of Physiology in Birds.

Long-term programmed rheostatic changes in physiology are essential for animal fitness. Hypothalamic nuclei and the pituitary gland govern key developmental and seasonal transitions in reproduction. The aim of this study was to identify the molecular substrates that are common and unique to developmental and seasonal timing. Adult and juvenile quail were collected from reproductively mature and immature states, and key molecular targets were examined in the mediobasal hypothalamus (MBH) and pituitary gland. qRT-PCR assays established deiodinase type 2 (DIO2) and type 3 (DIO3) expression in adults changed with photoperiod manipulations. However, DIO2 and DIO3 remain constitutively expressed in juveniles. Pituitary gland transcriptome analyses established that 340 transcripts were differentially expressed across seasonal photoperiod programs and 1,189 transcripts displayed age-dependent variation in expression. Prolactin (PRL) and follicle-stimulating hormone subunit beta (FSHß) are molecular markers of seasonal programs and are significantly upregulated in long photoperiod conditions. Growth hormone expression was significantly upregulated in juvenile quail, regardless of photoperiodic condition. These findings indicate that a level of cell autonomy in the pituitary gland governs seasonal and developmental programs in physiology. Overall, this paper yields novel insights into the molecular mechanisms that govern developmental programs and adult brain plasticity.

IGFBP1a is a nutrient deficient response factor that can inhibit fish reproduction through the hypothalamus-pituitary-ovary axis†.

Reproduction is a high energy consuming process, so long-term malnutrition can significantly inhibit gonadal development. However, little is known about the molecular mechanism by which fasting inhibits reproduction. Our present study found that fasting could dramatically induce insulin-like growth factor binding protein 1 (IGFBP1) expression in the liver, hypothalamus, pituitary and ovaries of grass carp. In addition, IGFBP1a in the hypothalamus-pituitary-gonad axis could inhibit the development of gonads. These results indicated that fasting may participate in the regulation of fish gonadal development through the mediation of IGFBP1a. Further studies found that IGFBP1a could markedly inhibit gonadotropin-releasing hormone 3 expressions in hypothalamus cells. At the pituitary level, IGFBP1a could significantly reduce the gonadotropin hormones (LH and FSH) expression by blocking the action of pituitary insulin-like growth factor 1. Interestingly, IGFBP1a could also directly inhibit the expression of lhr, fshr, and sex steroid hormone synthase genes (cyp11a, cyp17a, and cyp19a1) in the ovary. These results indicated that IGFBP1a should be a nutrient deficient response factor that could inhibit fish reproduction through the hypothalamus-pituitary-ovary axis.

Salivary testosterone and cortisol response in acute stress modulated by seven sessions of mindfulness meditation in young males.

Stress is an established risk factor for negative health outcomes. Salivary cortisol and testosterone concentrations increase in response to acute psychosocial stress. It's crucial to reduce stress for health and well-being through evidence-based interventions. Body-mind interventions such as meditation and Tai Chi have shown reduced cortisol levels but mixed results in testosterone concentration after stress. To address this research gap, we conducted a pilot randomized controlled trial to examine the modulating effects of a short-term (seven 20-minute sessions) mindfulness meditation on testosterone and cortisol in response to acute stress. Using one form of mindfulness meditation - Integrative Body-Mind Training (IBMT) and an active control-relaxation training (RT), we assessed salivary cortisol and testosterone concentrations at three stages of stress intervention - rest, stress, and an additional 20-min IBMT or RT practice. We found increased cortisol and testosterone concentrations after acute stress in both groups, but testosterone rise was not associated with cortisol rise. Moreover, an additional practice immediately after stress produced higher testosterone concentrations in the IBMT group than the RT group, whereas cortisol concentration increased in the RT group than in the IBMT group at the same time point. These findings indicate that brief mindfulness intervention modulates a dual-hormone profile of testosterone and cortisol in response to acute stress presumably via the co-regulation of hypothalamus-pituitary-adrenal and hypothalamus-pituitary-testicular axes.

Microsurgical Resection of a Parachiasmatic Craniopharyngioma via a Left-Sided Pterional Transsylvian Approach.

Craniopharyngiomas are histologically benign tumors that originate from squamous rests along the pituitary stalk. They make up approximately 1.2% to 4.6% of all intracranial tumors and do not show significant differences in occurrence based on sex. Adamantinomatous craniopharyngiomas have 2 peaks of incidence, commonly observed in patients from ages 5 to 15 years and again from 45 to 60 years. In contrast, papillary craniopharyngiomas mainly affect adults in their fifth and sixth decades of life.1 The "malignancy" of craniopharyngiomas is attributed to their location and the challenges associated with achieving complete removal because they can manifest in the sellar, parachiasmatic, and intraventricular regions or a combination of these.2,3 Various approaches have been used to resect these tumors.4,5 Radical resection offers the most promising option for disease control, potential cure, and the ability to transform the disease from lethal to survivable in children, allowing for a functional adult life.2,3 Meticulous evaluation is crucial to determine the appropriate approach and side, with particular emphasis on closely examining the relationship between the tumor and optic pathways (nerve, chiasm, tract), which are frequently involved. This assessment should also include the tumor's relationship with other crucial structures, such as the hypothalamus and adjacent arteries, to ensure that the strategy is adjusted accordingly to further minimize the risk of postoperative morbidity. Video 1 demonstrates a left-sided pterional transsylvian approach to remove a parachiasmatic craniopharyngioma involving the left optic chiasm and tract.

Transcriptomic analysis of the HPG axis-related tissues reveals potential candidate genes and regulatory pathways associated with testicular size in Hu sheep.

Testicular size is an excellent proxy for selecting high-fertility rams. The hypothalamus-pituitary-gonadal (HPG) axis plays an important role in regulating reproductive capacity in vertebrates, while key genes and regulatory pathways within the HPG axis associated with testicular size remain largely unknown in sheep. This study comprehensively compared the transcriptomic profiles in the hypothalamus, pituitary and testis of rams after sexual maturity between the large-testis group (LTG, testicular weight = 454.29 ± 54.24 g) and the small-testis group (STG, testicular weight = 77.29 ± 10.76 g). In total, 914, 795 and 10518 differentially expressed genes (DEGs) were identified in the hypothalamus, pituitary and testis between LTG and STG, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that these DEGs were mainly involved in the biological processes of reproduction, biological regulation, and development process. Notably, the neuroactive ligand-receptor interaction and cAMP signaling pathways, commonly enriched by the DEGs in the hypothalamus and pituitary between two groups, were considered as two key signal pathways regulating testicular development through the HPGs axis. Weighted gene co-expression network analysis (WGCNA) identified two modules that were significantly associated with testicular size, and 97 key genes were selected with high module membership (MM) and gene significance (GS) in these two modules. Finally, a protein-protein interaction (PPI) network was constructed, and ten genes with the highest degree were represented as hub genes, including FOS, NPY, SST, F2, AGT, NTS, OXT, EDN1, VIP and TAC1. Taken together, these results provide new insights into the molecular mechanism underlying the HPG axis regulating testicular size of Hu sheep.

Selenium protects against nesfatin-1 modulation of the hypothalamic-pituitary-testicular axis during hypothyroidism in male rats.

Normal gonadal function can be disrupted by hypothyroidism. Hypothyroidism disturbs testicular function directly and centrally by affecting the hypothalamic-pituitary-testicular axis with unclear mechanism. As nesfatin-1 neurons co-localized with TRH and GnRH neurons in the hypothalamus, it could play a role in centrally hypothyroidism induced testicular dysfunction. Selenium (Se), by affecting thyroid iodide supply, could relieve these disturbances. So, we aim to identify the role of nesfatin-1 as a link between testicular dysfunction and hypothyroidism through modulating the MAPK/ERK pathway while discussing the possible role of Se in alleviating hypothyroidism and associated testicular damage. Forty male rats were divided equally into: Control: distilled water, Se: Se orally, Propylthiouracil (PTU): PTU orally, PTU + Se: Se with PTU orally. Serum thyroid function, gonadal hormones, nesfatin-1, testicular redox status, sperm analysis, brain tissue GnRH, nucleobindin 2-derived polypeptide, pMAPK/ERK gene expression, histological changes and immunohistochemical expression of testicular proliferating cell antigen (PCNA) were done. PTU induced hypothyroidism and reduction of gonadal hormones which both were correlated with reduced nesfatin-1. There was testicular stress with reduced GnRH, NUCB2, pMAPK/ERK gene expression, and PCNA immunopositive cells. These parameters were reversed by Se. Nesfatin-1 could be the central link between hypothyroidism and disturbances of the hypothalamic pituitary testicular axis.

Efficacy of the spirit-regulation method of Jin's three-needle therapy for post-stroke anxiety and its effect on the hypothalamus-pituitary-adrenal axis. / 靳三针调神针法治疗卒中后焦虑的疗效观察及对下丘脑-垂体-è‚¾ä¸Šè ºè½´çš„å½±å“.

OBJECTIVES: To observe the clinical efficacy of the spirit-regulation method of Jin's three-needle therapy on post-stroke anxiety and its effects on the hypothalamus-pituitary-adrenal (HPA) axis. METHODS: Fifty-four patients with post-stroke anxiety were divided into spirit regulation (Jin's three needle therapy) group and sham-acupuncture group according to the random number table method, 28 cases in the spirit regulation and 26 cases in the sham-acupuncture group. The patients of the two groups received the same regimen of basic medication and rehabilitation, and the same acupoint prescription was adopted, including Sishenzhen (extra points, 1.5 cun to Baihui ［GV20］ at 3, 6, 9 and 12 o'clock positions), Shenting (GV24), Yintang (EX-HN3), and bilateral Shenmen (HT7), Sanyinjiao (SP6), Hegu (LI4) and Taichong (LR3). The true acupuncture was delivered in the spirit regulation group and the sham acupuncture operated in the sham-acupuncture group. One treatment lasted for 30 min, once daily, 5 times a week. The duration of treatment was 3 weeks in the trial. Before treatment and on day 10 and day 21 of treatment, the changes in the score of Hamilton anxiety scale (HAMA) and that of National Institutes of Health Stroke Scale (NIHSS) were compared between the two groups separately. Using ELISA, the contents of adrenocorticotropin (ACTH) and cortisol (CORT) in the serum were detected, and the adverse reactions were recorded. RESULTS: In the within-group comparison before and after treatment, HAMA score and NIHSS score dropped on day 10 and day 21 after treatment in the spirit regulation group (P<0.05)；HAMA score and NIHSS score in the sham-acupuncture group were decreased on day 21 of treatment (P<0.05). After 21 days of treatment, HAMA score and NIHSS score in the spirit-regulation group were decreased significantly than those in the sham-acupuncture group (P<0.05) and the contents of ACTH and CORT in the serum decreased when compared with those before treatment and those of the sham-operation group (P<0.05). No obvious adverse events occurred in the spirit-regulation group and the sham-acupuncture group. CONCLUSIONS: Using sham acupuncture as a control, it is preliminarily confirmed that the spirit regulation method of Jin's three-needle therapy is effective on post-stroke anxiety. In association of the downtrend of serological indicators, it is speculated that the underlying mechanism of this therapy is related to HPA axis.

A microscale 3D organ on a chip for recapitulating reciprocal neuroendocrine crosstalk between the hypothalamus and the pituitary gland.

Conventional 2D or even recently developed 3Din vitroculture models for hypothalamus and pituitary gland cannot successfully recapitulate reciprocal neuroendocrine communications between these two pivotal neuroendocrine tissues known to play an essential role in controlling the body's endocrine system, survival, and reproduction. In addition, most currentvitroculture models for neuroendocrine tissues fail to properly reflect their complex multicellular structure. In this context, we developed a novel microscale chip platform, termed the 'hypothalamic-pituitary (HP) axis-on-a-chip,' which integrates various cellular components of the hypothalamus and pituitary gland with biomaterials such as collagen and hyaluronic acid. We used non-toxic blood coagulation factors (fibrinogen and thrombin) as natural cross-linking agents to increase the mechanical strength of biomaterials without showing residual toxicity to overcome drawbacks of conventional chemical cross-linking agents. Furthermore, we identified and verified SERPINB2 as a reliable neuroendocrine toxic marker, with its expression significantly increased in both hypothalamus and pituitary gland cells following exposure to various types of toxins. Next, we introduced SERPINB2-fluorescence reporter system into loaded hypothalamic cells and pituitary gland cells within each chamber of the HP axis on a chip, respectively. By incorporating this SERPINB2 detection system into the loaded hypothalamic and pituitary gland cells within our chip platform, Our HP axis-on-chip platform can better mimic reciprocal neuroendocrine crosstalk between the hypothalamus and the pituitary gland in the brain microenvironments with improved efficiency in evaluating neuroendocrine toxicities of certain drug candidates.

Changes in pituitary gonadotropin subunits and hypothalamic Kiss-1 gene expression by administration of sex steroids in ovary-intact female rats.

OBJECTIVE: We examined how the sex steroids influence the synthesis of gonadotropins. MATERIALS AND METHODS: The effects of sex steroids estradiol (E2), progesterone (P4), and dihydrotestosterone (DHT) in pituitary gonadotroph cell model (LßT2 cells) in vitro and ovary-intact rats in vivo were examined. The effects of sex steroids on Kiss1 gene expression in the hypothalamus were also examined in ovary-intact rats. RESULTS: In LßT2 cells, E2 increased common glycoprotein alpha (Cga) and luteinizing hormone beta (Lhb) subunit promoter activity as well as their mRNA expression. Although gonadotropin subunit promoter activity was not modulated by P4, Cga and Lhb mRNA expression was increased by P4. DHT inhibited Cga and Lhb mRNA expression with a concomitant decrease in their promoter activity. During the 2-week administration of exogenous E2 to ovary-intact rats, the estrous cycle determined by vaginal smears was disrupted. P4 or DHT administration completely eliminated the estrous cycle. Protein expression of all three gonadotropin subunits within the pituitary gland was inhibited by E2 or P4 treatment in vivo; however, DHT reduced Cga expression but did not modulate Lhb or follicle-stimulating hormone beta subunit expression. E2 administration significantly repressed Kiss1 mRNA expression in a posterior hypothalamic region that included the arcuate nucleus. P4 and DHT did not modulate Kiss1 mRNA expression in this region. In contrast, P4 administration significantly inhibited Kiss1 mRNA expression in the anterior region of the hypothalamus that included the anteroventral periventricular nucleus. The expression of gonadotropin-releasing hormone (Gnrh) mRNA in the anterior hypothalamic region, where the preoptic area is located, appeared to be decreased by treatment with E2 and P4. CONCLUSION: Our findings suggest that sex steroids have different effects in the hypothalamus and pituitary gland.

Hypothalamic-pituitary dysfunction in Sturge-Weber syndrome: case report and review of the literature.

OBJECTIVES: Sturge-Weber syndrome (SWS) is a rare neurocutaneous disorder that is characterized by a segmental dermatomal facial port-wine stain birthmark and is frequently accompanied by ipsilateral brain and eye abnormalities. We present a case of a patient with SWS who exhibited hypogonadotropic hypogonadism, growth hormone (GH) deficiency, and central hypothyroidism at the age of 20 despite the absence of radiographic findings in the pituitary and hypothalamus. CASE PRESENTATION: A 20-year-old male with SWS with epilepsy and Klippel-Trenaunay syndrome presents with delayed pubertal development, short stature, and obesity. Upon further examination, he was found to have biochemical and clinical evidence of hypogonadism, hypothyroidism, and GH deficiency. A pituitary MRI displayed no abnormalities of the pituitary or hypothalamus. Treatment with testosterone cypionate and levothyroxine was initiated. Despite successful pubertal induction, IGF-1 levels have remained low and treatment with recombinant human growth hormone (rhGH) is now being considered for metabolic benefits. CONCLUSIONS: This case emphasizes the importance of endocrine evaluation and treatment of hormonal deficiencies in patients with SWS despite the absence of radiographic findings.

Therapeutic effects of melatonin in female mice with central precocious puberty by regulating the hypothalamic Kiss-1/Kiss1R system.

In recent years, central precocious puberty (CPP) in children is becoming more common, which seriously affects their physical and psychological health and requires finding a safe and effective treatment method. The aim of this study was to investigate the therapeutic effect of melatonin on CPP. A CPP model was established by subcutaneous injection of 300 micrograms of danazol into 5-day-old female mice, followed by treatment with melatonin and leuprolide. The vaginal opening was checked daily. Mice were weighed, gonads were weighed, gonadal index was calculated, and gonadal development was observed by hematoxylin and eosin (HE) staining. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) levels were measured by ELISA. By using RT-PCR and Western blotting, the mRNA and protein expression of the hypothalamus Kiss-1, Kiss-1 receptor (Kiss1R), gonadotropin-releasing hormone (GnRH), and pituitary GnRH receptor (GnRHR) were identified. The results showed that melatonin delayed vaginal opening time and reduced body weight, gonadal weight and indices in female CPP mice. Melatonin treatment prevents uterine wall thickening and ovarian luteinization in female CPP mice. Melatonin treatment reduces serum concentrations of FSH, LH, and E2 in female CPP mice. Melatonin suppressed the expressions of Kiss-1, Kiss1R and GnRH in the hypothalamus, and the expression of GnRHR in the pituitary of the female CPP mice. Our results suggest that melatonin can inhibit the hypothalamic-pituitary-gonadal (HPG) axis by down-regulating the Kiss-1/Kiss1R system, thereby treating CPP in female mice.

Pediatric craniopharyngiomas: magnetic resonance imaging assessment for hypothalamus-pituitary axis dysfunction and outcome prediction.

BACKGROUND: In adamantinomatous craniopharyngiomas, tumor topographical categories, cystic component volume, and magnetic resonance signal intensity may impact prognosis. OBJECTIVE: To identify magnetic resonance imaging (MRI) variables associated with pituitary-hypothalamic axis dysfunction and predictive of outcome in children with cystic adamantinomatous craniopharyngiomas. MATERIALS AND METHODS: We evaluated 40 preoperative MRIs of adamantinomatous craniopharyngiomas to classify tumor topography, volume, and signal intensity of the cystic components and peritumoral edema. Volumes and normalized signal intensity minimum values were extracted from coronal T2-weighted images (nT2min). Radiological variables were compared to pituitary-hypothalamic axis dysfunction-related clinical data and surgical outcomes. RESULTS: Adamantinomatous craniopharyngiomas were categorized into five topographic classes (12 patients, sellar-suprasellar; seven patients, pseudo-intraventricular; six patients, strict intraventricular; 14 patients, secondary intraventricular; one patient, not strict intraventricular). All cases exhibited a predominant (30 patients, 80%) or total (10 patients, 20%) cystic tumor component and displayed low nT2min percentage values compared to cerebrospinal fluid (42.3% [interquartile range 28.4-54.6%]). Significant associations between tumor topographic classes and pituitary dysfunction (P<0.001), and between peritumoral edema and hypothalamic dysfunction (P<0.001) were found. Considering extent of surgical removal and tumor relapse, volume of the cystic tumor component displayed a positive correlation (P=0.002; r=0.48; P=0.02; r=0.36), while nT2min intensity values exhibited a negative correlation (P=0.01; r= - 0.40; P=0.028; r= - 0.34). CONCLUSION: Severe hypothalamic-pituitary axis dysfunction is associated with tumors along the pituitary stalk and peritumoral edema. Tumor invasion of the third ventricle, tight adherence to the hypothalamus, larger volumes, and lower nT2min intensity of the tumor cystic component are independent predictors of extent of adamantinomatous craniopharyngioma excision and recurrence.

Regulation of circulating thyroid hormone levels by hypothalamic tanycytes and hypophysial pars tuberalis-specific cells and their morphological and gene- and protein-expression changes under different photoperiods.

Thyroid hormone in the hypothalamus acts as a key determinant of seasonal transitions. Thyroid hormone-levels in the brain are mainly regulated by the hypothalamic tanycytes and pituitary pars tuberalis (PT)-specific cells. TSHß produced by the PT-specific cells stimulates Dio2 expression and decreases Dio3 expression of the tanycytes. Both tanycytes and PT-specific cells in photosensitive animals exhibit remarkable changes of morphological appearance and expressions of genes and proteins under different photoperiods. Long photoperiods induce increased gene- and protein-expressions and active features. Short photoperiods cause the decreased gene- and protein-expressions and inactive features. In the PT, expressions of TSHß, common α-subunit of glycoprotein hormones (α-GSU), and MT1 receptor of melatonin receptors and eyes absent 3 change under different photoperiods. Diurnal rhythms of α-GSU mRNA expression are observed in the PT of Djungarian hamsters. Hes1, Nkx2.1, and LIM homeodomain gene 2 (Lhx2) are involved in the differentiation of PT. In the hypothalamic tanycytes, expressions of Dio2, Dio3, vimentin, serine/threonine kinase 33, GPR50, Nestin, Retinoid signaling genes (retinaldehyde dehydrogenase 1, cellular retinol binding protein 1, and Stra6), monocarboxylate transporter 8, and neural cell adhesion molecule change under different photoperiods. Rax, Lhx2, Nfia/b/x, and fibroblast growth factor 10 are involved in the differentiation of tanycytes.

[Change of the retinoic acid pathway in hypothalamus and pituitary damage induced by combined exposure to low-level Pb~(2+) and 1-nitropyrene in mice].

OBJECTIVE: To observe the expression of the retinoic acid(RA) pathway in hypothalamus and pituitary damage induced by combined exposure of low-level lead and 1-nitropyrene in mice, and to explore the relationship between the changes of RA pathway and hypothalamus and pituitary damage. METHODS: A total of 84 4-week-old ICR mice were randomly divided into the control group, Pb~(2+) tainted group(0.008 mg/L), 1-NP tainted group(0.1 mg/kg), low(0.008 mg/L Pb~(2+)+0.004 mg/kg 1-NP), medium(0.008 mg/L Pb~(2+)+0.02 mg/kg 1-NP), and high-dose co-toxicity group(0.008 mg/L Pb~(2+)+0.1 mg/kg 1-NP) according to body weight, with 14 mice in each group. Among them, Pb~(2+) was provided by lead acetate, added to deionized water and ingested by mice drinking freely, 1-NP was given by intraperitoneal injection, 1-NP was administered by intraperitoneal injection. Record daily water intake and food intake. After 21 consecutive days of exposure, body mass was measured, histological changes in the hypothalamus and pituitary were observed under an optical microscope, and lead content in brain tissue was measured by atomic absorption spectrometry. The real-time fluorescence quantitative PCR was used to detect the abundance of retinoic acid pathway members and c-Jun N-terminal kinases genes(Jnks), and the western blot method was used to detect expression levels of acetaldehyde dehydrogenase 2(ALDH2), cytochrome P450 family member 26A1(CYP26a1) proteins. RESULTS: There was no difference in the mean weekly water intake and food intake of the mice in each group. The body weight of the high-dose co-toxicity group mice((27.4±1.9)g) was lower than that of the control group((29.8±2.3)g)(P<0.05). The level of serum follicle-stimulating hormone(FSH) in the middle and high dose co-toxicity groups((265.01±2.99), (260.42±3.61)pg/mL, respectively) was lower than that in the control group((279.00±1.30)pg/mL, P<0.05). The content of Pb~(2+) in the brain of each group containing Pb~(2+) was higher than that of the control group. In the hypothalamic and pituitary tissues, the abundance of Adh1, Adh2, Rar and Rxr, and ALDH2 levels in the medium and high dose co-toxicity groups were higher than those in the control group(P<0.05). Cyp26a1 gene abundance and protein levels were lower in the medium and high dose co-toxicity groups than in the control group(P<0.05). The abundance of Jnks in the high-dose co-toxicity group was higher than that in the control group(P<0.05). CONCLUSION: Continuous exposure to 0.008 mg/L Pb~(2+)+0.1 mg/kg 1-NP for 21 days can cause damage to the hypothalamus and pituitary of mice, and activate the RA signaling pathway.

Transcriptome analysis of hypothalamus and pituitary tissues reveals genetic mechanisms associated with high egg production rates in Changshun green-shell laying hens.

BACKGROUND: Changshun green-shell laying hens are unique to the Guizhou Province, China, and have high egg quality but relatively low yield. Egg production traits are regulated by the hypothalamus-pituitary-ovary axis. However, the underlying mechanism remains unclear. Thus, we conducted RNA sequencing of hypothalamic and pituitary tissues from low- and high-yielding Changshun green-shell laying hens to identify critical pathways and candidate genes involved in controlling the egg production rate. RESULTS: More than 39 million clean reads per sample were obtained, and more than 82% were mapped to the Gallus gallus genome. Further analysis identified 1,817 and 1,171 differentially expressed genes (DEGs) in the hypothalamus and pituitary, respectively. Nineteen DEGs were upregulated in both the hypothalamus and pituitary of high-yielding chickens. The functions of these DEGs were mainly associated with ion transport or signal transduction. Gene set enrichment analysis revealed that the pathways enriched in the hypothalamus were mainly associated with gonadotropin-releasing hormone (GnRH) secretion, neurotransmitter release, and circadian rhythms. The pathways enriched in the pituitary were mainly associated with GnRH secretion, energy metabolism, and signal transduction. Five and four DEGs in the hypothalamus and pituitary, respectively, were selected randomly for qRT-PCR analysis. The expression trends determined via qRT-PCR were consistent with the RNA-seq results. CONCLUSIONS: The current study identified 19 DEGs upregulated in both the hypothalamus and pituitary gland, which could provide an important reference for further studies on the molecular mechanisms underlying egg production in Changshun green-shell laying hens. In addition, enrichment analysis showed that GnRH secretion and signal transduction, especially neurotransmitter release, play crucial roles in the regulation of egg production.

A 36-Year-Old Woman With an Unexpected Cause of Hypokalemia.

A 36-year-old woman complained of bilateral lower limb weakness for the last 3 days. She could move her upper limb, neck, and facial muscles and had no respiratory or swallowing difficulties. About 4 years ago, she complained of sudden weakness involving her lower limbs. Two years later, she had another episode involving only the right upper limb. In both cases, she was hypokalemic and received oral and intravenous potassium. She is a known diabetic and has polycystic ovary disease. Her blood pressure was 150/100 mm Hg, and body mass index was 29. Her serum potassium was 2 mEq/L, plasma renin 5 ng/dL, plasma aldosterone 0.63 µIU/mL, and aldosterone to plasma renin activity ratio 8. Cushing syndrome was considered a possibility. Subsequent analysis indicated a baseline cortisol level of 19.6 µg/dL at 8 Am. A screening overnight 1-mg dexamethasone suppression test (DST) showed 17 µg/dL cortisol. The low-dose DST revealed a cortisol level of 10.8 µg/dL. Adrenocorticotropin level was 196 pg/mL, and 24-hour urinary cortisol level was 1284 mg/dL. A high dose of 8-mg DST at 11 Pm to find the source of hypercortisolism performed yielded 15.9 µg/dL. Magnetic resonance imaging of the pituitary displayed a well-defined, heterogeneously enhanced mass lesion (15 × 13 × 11 mm) in the sella with mild suprasellar extension. Transsphenoidal resection and stereotactic radiosurgery were performed on the tumor with hormone replacement and glycemic control following surgery.

Correlational Study of Aminopeptidase Activities between Left or Right Frontal Cortex versus the Hypothalamus, Pituitary, Adrenal Axis of Spontaneously Hypertensive Rats Treated with Hypotensive or Hypertensive Agents.

It has been suggested that the neuro-visceral integration works asymmetrically and that this asymmetry is dynamic and modifiable by physio-pathological influences. Aminopeptidases of the renin-angiotensin system (angiotensinases) have been shown to be modifiable under such conditions. This article analyzes the interactions of these angiotensinases between the left or right frontal cortex (FC) and the same enzymes in the hypothalamus (HT), pituitary (PT), adrenal (AD) axis (HPA) in control spontaneously hypertensive rats (SHR), in SHR treated with a hypotensive agent in the form of captopril (an angiotensin-converting enzyme inhibitor), and in SHR treated with a hypertensive agent in the form of the L-Arginine hypertensive analogue L-NG-Nitroarginine Methyl Ester (L-NAME). In the control SHR, there were significant negative correlations between the right FC with HPA and positive correlations between the left FC and HPA. In the captopril group, the predominance of negative correlations between the right FC and HPA and positive correlations between the HPA and left FC was maintained. In the L-NAME group, a radical change in all types of interactions was observed; particularly, there was an inversion in the predominance of negative correlations between the HPA and left FC. These results indicated a better balance of neuro-visceral interactions after captopril treatment and an increase in these interactions in the hypertensive animals, especially in those treated with L-NAME.