Thyroglobulin is the most important and abundant protein in thyroid follicles and has been widely studied as a tumor marker of thyroid cancer recurrence and persistence. Tg is considered the material basis of thyroid hormone synthesis and does not participate in the regulation of thyroid hormone synthesis and secretion. This review summarizes the recent progress in the research of thyroid hormone synthesis and secretion regulation via a negative feedback regulation mechanism by the thyroid-hypothalamus-pituitary axis. Thyroglobulin can negatively regulate the synthesis of thyroid hormone by thyroid follicular cells and antagonize the positive regulation of thyrotropin TSH. The function of thyroid follicular cells is presumably a result of Tg and TSH interaction, and a follicular cycle model is proposed to explain the causes of follicular heterogeneity in glands. We also discuss the prospects and clinical significance of studies into the negative feedback regulation mechanism of the thyroid-hypothalamus-pituitary axis and compare two theories for this mechanism.
Feedback, Physiological ; Humans ; Hypothalamo-Hypophyseal System ; physiology ; Neoplasm Recurrence, Local ; Thyroglobulin ; metabolism ; Thyroid Gland ; physiology ; Thyroid Hormones ; metabolism ; Thyrotropin ; metabolism

Objective: To explore the developmental characteristics of circadian rhythms in hypothalamus-pituitary-adrenal (HPA) axis during puberty. Methods: A total of 1 070 students from Grade 2-3 in 3 primary schools in Ma'anshan city, Anhui province, were selected for physical examination and circadian rhythm of HPA axis checked from 2015 to 2017. Saliva samples were collected at each of the following three time points: immediately upon wakening, 30 minutes after wakening and bedtime, with the index of circadian rhythm of HPA axis calculated, which including cortisol awake response (CAR), cortisol in puberty priming and diurnal cortisol slope (DCS). Testicular volume, palpation and visual inspection of breast development were used to assess the state of purbety development on boys and girls. Information on gender, date of birth, time to fall asleep, wake-up time and weekly physical activity were gathered through questionnaire survey. Non-parametric test was used to compare the differences of baseline, follow-up period and different adolescent developmental processes of each index on circadian rhythm of HPA axis. Results: During the period of follow-up program and comparing with the continuous undeveloped group, CAR and the changes of CAR showed significantly increase, both in the puberty priming group and continuous development group, with statistically significant differences (CAR: Z=8.551, 4.680, respectively; P<0.01; the changes of CAR: Z=4.079, 2.700, respectively, P<0.01). There were no significant differences noticed in CAR and the changes of CAR between puberty priming group or continuous development group. The area under the curve (AUC) of cortisol in puberty priming group was slightly higher than that in the persistent undeveloped group (Z=2.591, P=0.010). Both the changes of daily cortisol slope (DCS) in puberty priming group and continuing developed group decreased significantly, when comparing with those in continuous undeveloped group (Z=-2.450, Z=-2.151; all P<0.05). There was no significant difference noticed in the changes of cortisol in puberty priming and DCS between different puberty development stages (the changes of AUC: χ(2)=2.747, P=0.253; DCS: χ(2)=4.554, P=0.032). Conclusions: The indexes of circadian rhythm of HPA axis were associated with the development of puberty. Both the cortisol awakening response and the total amount of diurnal cortisol secretion showed an increase, along with the puberty development. The change of diurnal cortisol slope declined with the development of puberty.
Adolescent ; Area Under Curve ; Circadian Rhythm ; Female ; Humans ; Hydrocortisone ; Hypothalamo-Hypophyseal System ; Male ; Pituitary-Adrenal System ; Pregnancy ; Saliva ; Sexual Maturation/physiology* ; Surveys and Questionnaires ; Wakefulness

OBJECTIVETo systematically review the updated information about the gut microbiota-brain axis.

DATA SOURCESAll articles about gut microbiota-brain axis published up to July 18, 2016, were identified through a literature search on PubMed, ScienceDirect, and Web of Science, with the keywords of "gut microbiota", "gut-brain axis", and "neuroscience".

STUDY SELECTIONAll relevant articles on gut microbiota and gut-brain axis were included and carefully reviewed, with no limitation of study design.

RESULTSIt is well-recognized that gut microbiota affects the brain's physiological, behavioral, and cognitive functions although its precise mechanism has not yet been fully understood. Gut microbiota-brain axis may include gut microbiota and their metabolic products, enteric nervous system, sympathetic and parasympathetic branches within the autonomic nervous system, neural-immune system, neuroendocrine system, and central nervous system. Moreover, there may be five communication routes between gut microbiota and brain, including the gut-brain's neural network, neuroendocrine-hypothalamic-pituitary-adrenal axis, gut immune system, some neurotransmitters and neural regulators synthesized by gut bacteria, and barrier paths including intestinal mucosal barrier and blood-brain barrier. The microbiome is used to define the composition and functional characteristics of gut microbiota, and metagenomics is an appropriate technique to characterize gut microbiota.

CONCLUSIONSGut microbiota-brain axis refers to a bidirectional information network between the gut microbiota and the brain, which may provide a new way to protect the brain in the near future.

Animals ; Brain ; metabolism ; physiology ; Central Nervous System ; metabolism ; physiology ; Gastrointestinal Microbiome ; physiology ; Gastrointestinal Tract ; microbiology ; Humans ; Hypothalamo-Hypophyseal System ; metabolism ; physiology ; Pituitary-Adrenal System ; metabolism ; physiology

OBJECTIVETo study the relationship between the suppression of the hypothalamic-pituitary-gonadal axis (HPGA) and the predicted adult height (PAH) in girls with central precocious puberty (CPP) during the treatment with gonadotropin-releasing hormone analogue (GnRHa), in order to provide guidance for individualized GnRHa dose adjustment in clinical practice.

METHODSThe clinical data of 75 CPP girls were collected, and then height, bone age (BA), uterine and ovarian volumes, and peak luteinizing hormone (LH), peak follicle-stimulating hormone (FSH), and estradiol (E2) levels were recorded at different time points of GnRHa treatment. PAH at each time point was calculated. PAH improvement (ΔPAH=PAH-target height) and its relationship with the degree of HPGA suppression were analyzed. Threshold effect analysis was applied to determine the best HPGA suppression range forΔPAH.

RESULTSAfter GnRHa treatment, PAHs were improved markedly compared with the data in the early stage of treatment. ΔPAH showed a negative correlation with ΔBA. At 24 months of treatment, ΔPAH was also negatively correlated with LH. Uterine volume controlled between 2.3 and 3.0 mL, LH level controlled below 0.8 IU/L, and FSH controlled below 2.4 IU/L could slow down the growth of BA and improve PAH.

CONCLUSIONSGnRHa treatment can improve the PAH of CPP girls. Selection of an appropriate therapeutic dose for GnRHa to control uterine volume, LH and FSH levels within certain ranges can slow down the growth of BA and improve PAH.

Adult ; Body Height ; Child ; Female ; Follicle Stimulating Hormone ; blood ; Gonadotropin-Releasing Hormone ; analogs & derivatives ; Humans ; Hypothalamo-Hypophyseal System ; physiology ; Luteinizing Hormone ; blood ; Ovary ; physiology ; Puberty, Precocious ; blood ; drug therapy ; physiopathology ; Retrospective Studies

This study was aimed to investigate the changes of the hypothalamic-pituitary-adrenal axis (HPAA) activity and the cytokines system in the hypothalamus of the depressive rats which were exposed to chronic unpredictable mild stressors (CUMS) after middle cerebral artery occlusion (MCAO). By means of qRT-PCR, ELISA and Western blot, mRNA and/or protein expressions of corticotropin releasing factor (CRF), tumor necrosis factors-α (TNF-α), suppressor of cytokines signaling 3 (SOCS3), phosphorylation of signal transducers and activators of transcription 3 (pSTAT3) were measured in the hypothalamus of rats. The results showed that, compared with control group, CUMS+MCAO group exhibited increased mRNA levels of CRF, TNF-α, SOCS3, as well as up-regulated CRF, TNF-α, SOCS3 and pSTAT3 protein expressions. Furthermore, there were correlations between CRF and TNF-α, TNF-α and SOCS3, SOCS3 and pSTAT3, respectively. These observations indicated the CRF system was activated in the post stroke depression (PSD) status. The TNF-α and its signaling pathway, STAT3/SOCS3, were up-regulated in mRNA and protein levels. In conclusion, this study presents the evidence which supports the hypothesis of signaling cross-talk between the CRF system and TNF-α signaling pathway after ischemic stroke and CUMS.
Animals ; Hypothalamo-Hypophyseal System ; physiology ; Hypothalamus ; physiology ; Infarction, Middle Cerebral Artery ; Phosphorylation ; Pituitary-Adrenal System ; physiology ; Rats ; STAT3 Transcription Factor ; metabolism ; Signal Transduction ; Suppressor of Cytokine Signaling 3 Protein ; Suppressor of Cytokine Signaling Proteins ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism ; Up-Regulation

Depression and insomnia are intimately related. Depressed patients usually manifest sleep discontinuity and early awakening, reduced or no slow wave sleep (SWS) and shortened latency of rapid eye movement (REM) sleep. These sleep abnormalities are very similar to those caused by over activated hypothalamic-pituitary-adrenal (HPA) axis with stress. Therefore, the animal models developed by post-traumatic stress disorder or chronic unpredictable mild stress could be used to evaluate drugs which have effects of both anti-depression and improvement of sleep quality, and to provide a more reliable platform for further studis on the mechanisms of depression and accompanied insomnia. This review mainly focuses on the typical features of sleep disturbance of depression, possible pathophysiological mechanisms, establishment of animal stress models and analysis of their abnormal sleep characteristics.
Animals ; Chronic Disease ; Depression ; physiopathology ; Depressive Disorder ; physiopathology ; Disease Models, Animal ; Humans ; Hypothalamo-Hypophyseal System ; physiopathology ; Pituitary-Adrenal System ; physiopathology ; Sleep ; physiology ; Sleep Initiation and Maintenance Disorders ; physiopathology ; Sleep, REM ; Stress Disorders, Post-Traumatic ; physiopathology ; Stress, Psychological ; physiopathology

PURPOSE: Cortisol awakening response (CAR) and nighttime cortisol levels have been used as indices of adrenocortical activity. However, population-based statistical information regarding these indices has not been provided in healthy subjects. This study was carried out to provide basic statistical information regarding these indices. MATERIALS AND METHODS: Cortisol levels were measured in saliva samples collected immediately upon awakening (0 min), 30 min after awakening and in the nighttime on two consecutive days in 133 healthy subjects. RESULTS: We determined the mean [standard deviation (SD)], median (interquartile range) and 5th-95th percentile range for each measure and auxiliary indices for CAR, i.e., the secreted cortisol concentration within 30 min of awakening (CARscc) and absolute and relative increases in cortisol level within 30 min of awakening (CARi and CARi%, respectively). We also determined these values for auxiliary indices derived from nighttime cortisol level, i.e., the ratio of cortisol level 30 min after awakening (CA30 min) to nighttime level (CA30 min/NC), as well as absolute and relative decreases in cortisol levels from CA30 min to nighttime (DCd and DCd%, respectively). We found no significant differences in cortisol level for any time point or in auxiliary indices between collection days, genders and ages. CONCLUSION: The provided descriptive information and statistics on the CAR and nighttime cortisol level will be helpful to medical specialists and researchers involved in hypothalamus-pituitary-adrenal axis assessment.
Adult ; Circadian Rhythm ; Female ; Humans ; Hydrocortisone/*metabolism ; Hypothalamo-Hypophyseal System/physiology ; Male ; Middle Aged ; Pituitary-Adrenal System/physiology ; Republic of Korea ; Saliva/*metabolism ; Wakefulness

OBJECTIVETo study the effects of early enriched environment on behavioral development and serum corticosterone level in rats.

METHODSForty-five neonatal rats were randomly assigned into three groups：blank control, enriched environment and isolated environment. The open-field environment test and the Lat maze test were performed to assess anxiety/irritability-related behaviors of the rats on postnatal day 31. The level of serum corticosterone was measured by radioimmunology assay.

RESULTSThe level of serum corticosterone in the enriched environment group (8±3 ng/mL) was significantly lower than the blank control (11±4 ng/mL) and the isolated groups (22±4 ng/mL) (P<0.01). The open-field environment test showed that the numbers of passing panels, keeping an erect posture and grooming were less than those in the blank control and the isolated groups (P<0.05). According to the results of the Lat maze test, the frequencies of running across the corner, keeping an erect posture and leaning against the wall in the enriched environment group were less than those in the blank control and the isolated groups (P<0.05).

CONCLUSIONSEarly enriched environment can decrease serum corticosterone level and thus alleviates anxiety and irritability in rats. It may play an important role in the improvement of brain development.

Animals ; Behavior, Animal ; Brain ; growth & development ; Corticosterone ; blood ; Environment ; Female ; Hypothalamo-Hypophyseal System ; physiology ; Maze Learning ; Pituitary-Adrenal System ; physiology ; Rats ; Rats, Sprague-Dawley

The Tibetan antelope, a prototype mammal, has developed a unique adaptation to extreme high altitude-associated hypoxia. To investigate the role of the endocrine system in adaptation to high altitude in the Tibetan antelope, comparisons of endocrine hormones levels between Tibetan antelope (n = 9) and Tibetan sheep (n = 10) were performed. Both two kinds of animals were captured at an altitude of 4 300 m and then transported to experimental base at 2 800 m altitude. The blood samples were drawn from right external jugular vein in the next morning, and the 20 hormones in hypothalamus-adenohypophysis-peripheral hormonal axis were measured with radioimmunoassay or enzyme-linked immunosorbent assay. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean pulmonary arterial pressure (mPAP) were recorded using catheterization. Moreover, hemoglobin (Hb) content was measured by blood analyser. The results showed that, the levels of FT(3), FT(4) and Ang II in Tibetan antelope were significantly lower than those in Tibetan sheep, whereas TRH, CRH, GHRH, F, E(2), Ald, ACTH and CGRP levels were significantly greater in Tibetan antelope than those in the Tibetan sheep. Compared with Tibetan sheep, Tibetan antelope showed lower HR, mPAP, SBP, DBP and Hb content. In Tibetan antelope and Tibetan sheep, both Hb and Ang II were correlated positively with respective mPAP. In Tibetan antelope, FT(3) level was correlated positively with GH and negatively with ACTH. These results suggest that the endocrine system of Tibetan antelope is characterized by low energy expenditure and high stress, which may be one of the mechanisms underlying the Tibetan antelope adaptation to chronic hypoxia.
Adaptation, Physiological ; physiology ; Altitude ; Animals ; Antelopes ; blood ; Hormones ; blood ; Hypothalamo-Hypophyseal System ; metabolism ; physiology ; Male ; Sheep ; blood ; Tibet

OBJECTIVETo study the functional and ultramicrostructural effects of alpha lipoic acid on hypothalamus-pituitary-adrenal (HPA) axis in normal and diabetic rats.

METHODSUsing radioimmunoassay we observed the effects of three doses (1, 20, and 100 mg/kg) of alpha lipoic acid injected intraperitoneally for 3 weeks on the plasma levels of CRH, ACTH and COR in normal and diabetic rats. The ultramicrostructural changes of the hypophysis and pituitary gland after alpha lipoic acid treatment were observed under transmission electron microscope.

RESULTSCompared with the control group, CRH level in lipoicin-treated normal and diabetic rats was significantly reduced (P<0.05). ACTH level of the 3 lipoicin doses groups of normal rats decreased, and a significant reduction occurred in medium-dose lipoicin group of diabetic rats (P<0.05). COR level showed the same changes as CRH level in normal rats, but decreased significantly in high- and medium-dose lipoicin groups of diabetic rats. Lipoicin treatment produced no apparent effect on the ultramicrostructures of the hypophysis and pituitary gland cells, which were the targets of diabetic lesions with low metabolism functions. Lipoicin treatment obviously enhanced the hypophysis and pituitary gland cell metabolism function to resist diabetic oxidative stress.

CONCLUSIONLipoicin can inhibit the HPA axis directly or indirectly in normal and diabetic rats.

Animals ; Diabetes Mellitus, Experimental ; pathology ; physiopathology ; Hypothalamo-Hypophyseal System ; drug effects ; physiology ; ultrastructure ; Male ; Pituitary-Adrenal System ; diagnostic imaging ; drug effects ; physiology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Thioctic Acid ; pharmacology ; Ultrasonography