Leptin, a peptide hormone secreted by adipocytes in proportion of the amount of energy stored in fat, plays a central role in regulating human energy homeostasis. In addition, leptin plays a significant permissive role in the physiological regulation of several neuroendocrine axes, including the hypothalamic-pituitary-gonadal, -thyroid, -growth hormone, and -adrenal axes. Decreased levels of leptin, also known as hypoleptinemia, signal to the brain a state of energy deprivation. Hypoleptinemia can be a congenital or acquired condition, and is associated with alterations of the aforementioned axes aimed at promoting survival. More specifically, gonadotropin levels decrease and become less pulsatile under conditions of energy deprivation, and these changes can be at least partially reversed through leptin administration in physiological replacement doses. Similarly, leptin deficiency is associated with thyroid axis abnormalities including abnormal levels of thyrotropin-releasing hormone, and leptin administration may at least partially attenuate this effect. Leptin deficiency results in decreased insulin-like growth factor 1 levels which can be partially ameliorated through leptin administration, and leptin appears to have a much more pronounced effect on the growth of rodents than that of humans. Similarly, adrenal axis function is regulated more tightly by low leptin in rodents than in humans. In addition to congenital leptin deficiency, conditions that may be associated with decreased leptin levels include hypothalamic amenorrhea, anorexia nervosa, and congenital or acquired lipodystrophy syndromes. Accumulating evidence from proof of concept studies suggests that leptin administration, in replacement doses, may ameliorate neuroendocrine abnormalities in individuals who suffer from these conditions.
Amenorrhea/metabolism ; Animals ; Female ; Humans ; Leptin/blood/deficiency/genetics/*metabolism ; Male ; Neurosecretory Systems/*metabolism

AIMTo elucidate the mechanism of depression induced by chronic unpredictable mild stress (CUMS), the effects of CUMS on serotonin (5-HT), tryptophan, stress hormones and behaviour were investigated in rats.

METHODSDepression was induced by for 8 weeks CUMS and confirmed by behavioral tests, the brain and plasma levels of monoamine neurotransmitters were analyzed by HPLC-ECD techniques, the content of plasma corticosterone was evaluated by I125 cortisol radioactivity immunoassay and the serum tryptophan content was measured by HTTACHI L-8800 amino acid analyzer.

RESULTS(1) Rats exposed to a series of mild, unpredictable stressors for 8 weeks displayed the decreased body weight, reduced scores of open-field test and preference of sucrose solution (P < 0.05). (2) Plasma and brain 5-HT contents in rats after exposure to CUMS 8 weeks decreased significantly (P < 0.05). While serum tryptophan content increased at the same time (P < 0.05). (3) Plasma norepinephrine and epinephrine in rats were increased after CUMS 8 weeks, but there was no difference between control and CUMS group in plasma corticosterone.

CONCLUSIONThe behavioral changes induced by CUMS for 8 weeks are similar to the features of human depression, which may be related to the disturbances of tryptophan metabolism induced by increased norepinephrine and epinephrine in CUMS rat.

Animals ; Depression ; metabolism ; Epinephrine ; metabolism ; Hippocampus ; metabolism ; Male ; Neurosecretory Systems ; metabolism ; Norepinephrine ; metabolism ; Rats ; Rats, Wistar ; Serotonin ; metabolism ; Stress, Psychological ; metabolism

The protein encoded by gene Nhlh2 (nescient helix-loop-helix 2, also known as HEN2 or NSCL2) is a new member of basic helix-loop-helix (bHLH) transcription factor family and is specifically expressed in nervous system, especially in neuroendocrine tissue. The homologous genes of Nhlh2 have been found in many eukaryotic organisms such as chicken, mouse, rat, cattle, and human. The functional researches of Nhlh2 are mainly focused on neuroendocrine system, retina development, and tumors. Some preliminary results have been obtained in the investigation of molecular regulation mechanism. This article summarizes the recent research advances in Nhlh2.
Animals ; Basic Helix-Loop-Helix Transcription Factors ; biosynthesis ; physiology ; Humans ; Neoplasms ; metabolism ; Nervous System ; metabolism ; Neurosecretory Systems ; metabolism ; Retina ; growth & development ; metabolism ; Species Specificity

Our previous studies document the expression of adrenoceptors and purinoceptors in the rat prostate neuroendocrine cells (RPNECs). However, a direct investigation of the receptors for acetylcholine (ACh) is still lacking in the prostate neuroendocrine cells. RPNECs were freshly isolated from the ventral lobes of rat prostate by using collagenase. Effects of ACh and various muscarinic antagonists on the intracellular Ca2+ concentration ([Ca2+]c ) were investigated by using the fura-2 spectrofluorimetry. Single-cell RT-PCR analysis was applied to identify the transcripts for the muscarinic receptor subtypes. ACh (5 micrometer) induced a sharp transient increase in the [Ca2+]c of RPNECs, which was independent of the extracellular Ca2+. In the same RPNECs, high KCl (60 mM), phenylephrine (5micrometer), UTP (P2Y1/2 agonist, 50, micrometer), and alpha, beta-meATP (P2X1/3 agonist, 0.5micrometer) also increased the [Ca2+]c. The ACh-induced [Ca2+]c change (delta[Ca2+]c ) was blocked by atropine or by para-fluorohexahydrosiladifenidol (M3 antagonist, 0.3micrometer), but not by telenzepine (M1 antagonist, 1 micrometer) and himbacine (M2 and M4 antagonist, 1 mircoM). The single-cell RT-PCR demonstrated the selective expression of mRNAs for M3 in RPNECs. In summary, RPNECs express M3 muscarinic receptors that are linked to the release of Ca2+ from intracellular stores. The Ca2+ signals of RPNECs might mediate the parasympathetic regulation of prostate gland.
Acetylcholine/pharmacology ; Animals ; Calcium/*metabolism ; Calcium Signaling ; Male ; Neurosecretory Systems/*metabolism ; Prostate/*metabolism ; Rats ; Rats, Sprague-Dawley ; Receptor, Muscarinic M3/*physiology ; Research Support, Non-U.S. Gov't

OBJECTIVE: Recent studies suggested that the neurotrophic effects might be a major therapeutic mechanism of antidepressants. However, these effects have not been confirmed yet in depressed patients. We investigated whether mirtazapine treatment has the neurotrophic effects in depressed patient by using (1)H-MRS and explored the relationship between these effects and clinical improvements and neuropsychological functions. METHODS: Fourteen female, right-handed patients with major depressive disorder and 12 healthy controls participated in the study. Before the treatment with mirtazapine, we measured severity of illness, neuropsychological functions, and the levels of NAA, Cho and Cr in both hippocampi using (1)H-MRS in the depressed subjects. After the treatment with mirtazapine for 6 weeks, we repeated the measures of the pretreatment condition in the depressed subjects. We also measured variables of severity of illness and hippocampal metabolites with (1)H-MRS in the control group. RESULTS: There were no significant differences in NAA/Cr, Cho/Cr, and Cho/NAA between the depressed subjects and the control group. However, after the treatment with mirtazapine, there were significant improvements in severity of illness, immediate memory, and delayed memory. The posttreatment ratio of the total hippocampal Cho/Cr was significantly lowered than the ratio of the pretreatment Cho/Cr. However, the percent changes of the hippocampal Cho/Cr from the pretreatment Cho/Cr ratio were not correlated with the changes of severity of illness or neuropsychological functions from the pretreatment condition. CONCLUSIONS: These findings indicate that mirtazapine may reduce the level of choline metabolites by stabilizing the effect on the cholinergic neurons, reducing turnover or metabolism of neuronal membranes, or modulating the neuroendocrine systems in the depressed patients. However, this effect is not necessarily related to clinical improvements. Further studies on the therapeutic action of mirtazapine are needed.
Antidepressive Agents ; Choline ; Cholinergic Neurons ; Depression* ; Depressive Disorder, Major ; Female* ; Hippocampus ; Humans ; Magnetic Resonance Spectroscopy ; Membranes ; Memory, Short-Term ; Metabolism ; Neurons ; Neurosecretory Systems ; Repression, Psychology

OBJECTIVETo explore the roles of intracellular cholesterol metabolism in neuroendocrine (NE) differentiation of prostate cancer based on an androgen-independent prostate cancer NE cell model induced by androgen deprivation.

METHODSLNCaP cells were cultured in androgen-depleted medium, and NE phenotypes were identified by observing the changes in cell morphology, molecular markers (SgIII, NSE and CgA) and cell proliferation. The expression and distribution of cholesterol and Sg III were determined by immunofluorescence staining. The expressions of the key genes LDL-R, SREBP-1 and SREBP-2 involved in cholesterol synthesis and uptake were detected by semi-quantitative RT-PCR.

RESULTSThe LNCaP cells showed shrinking bodies and extending axons after androgen deprivation, and all the molecular markers, such as Sg III, NSE and CgA, significantly increased in a time-dependent manner, while the cell proliferation was obviously inhibited (P < 0.05). The cholesterol distribution in the LNCaP cells after NE differentiation presented remarkable aggregation at the axon terminals. However, there were no significant differences in the expression of cholesterol between the two types of cells, nor in the changes of the expressions of key genes LDL-R, SREBP-1 and SREBP-2 involved in cholesterol synthesis and uptake (P > 0.05).

CONCLUSIONTransient androgen depletion could successfully induce NE differentiation of LNCaP cells, and the intracellular cholesterol could re-distribute into axon terminals to enhance the formation of neurosecretory granules.

Androgens ; pharmacology ; Cell Differentiation ; Cell Line, Tumor ; Cell Proliferation ; Cholesterol ; metabolism ; Humans ; Male ; Neurosecretory Systems ; metabolism ; Prostatic Neoplasms ; metabolism ; pathology ; Receptors, LDL ; metabolism ; Sterol Regulatory Element Binding Protein 1 ; metabolism ; Sterol Regulatory Element Binding Protein 2 ; metabolism

To elucidate the anti-depressive effect of Fufang Chaigui prescription and its mechanism and investigate its effect on neuroendocrine hormone, rats were included into a chronic unpredictable mild stress (CUMS) model for 28 d, and drugs were administered at the same time. During the period, rats' behaviors were observed and the blood was collected by using ELISA to determine representative hormone concentrations of HPAA, HPTA and HPGA. The changes in endogenous metabolites were analyzed by using H NMR metabolomics to seek the potential biomarkers. Results showed Fufang Chaigui prescription could improve the behaviors of CUMS rats obviously, increase contents of ACTH, CORT, T₃and decrease contents of TSH and TESTO and regulate the levels of lactate, α-glucose, choline, N-acetylglycoprotein, trimethylamine oxide and leucine to get closer to the contents of control group. The results of correlation analysis indicated that HPTA was associated with glycometabolism, amino acid metabolism and choline metabolism. And HPAA was related to glycometabolism and amino acid metabolism. However, HPGA was only correlated with glycometabolism. In conclusion, Fufang Chaigui prescription could show an obvious anti-depressive effect and its underlying mechanism might involve regulations of neuroendocrine function and pathways of glycometabolism, amino acid metabolism and choline metabolism.
Animals ; Antidepressive Agents ; administration & dosage ; Behavior, Animal ; Depression ; blood ; drug therapy ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Hormones ; metabolism ; Humans ; Male ; Metabolomics ; Neurosecretory Systems ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Serum ; chemistry ; metabolism

OBJECTIVEThe present study aims to study the influences experimental navigation and intensive exercise on immune-neuroendocrine network of the male rats and the effects of PNS to this influence.

METHODThirty 6-week Sprague-Dawley male rats (SD rats) were randomly located into three groups: Quiescent control (QC) group, training control (TC) group and Panax notoginseng saponins (PNS) group. Rats from QC group were not given any stimuli, and samples were taken after 7-day intragastric administration of saline. Rats from TC group underwent 10-day run training of increasing load on treadmill and received 7-day intragastric administration of saline. PNS group were subjected to the same procedure of run training as group TC, and received intragastric administration of PNS at the dose of 0.2 g x kg(-1). Blood samples were immediately obtained at the end of the tests to determine the serum levels of corticosterone (Cort), adrenocorticotropic hormone (ACTH), beta-endorphin (beta-EP), Neuropeptide Y (NPY) and interleukin-1beta (IL-1beta), interleukin-6 (IL-6) by RIA. Expressions of Pituitary ACTH, NPY were observed use the immunohistochemistry method and correlation analyses conducted. And the ultrastructural changes of the pituitaries and the adrenal cortex cells were examined by electron microscope meanwhile.

RESULTThe serum beta-EP and Cort levels in TC group were significantly increased compared to the QC group; whereas Expression levels of pituitary ACTH, NPY were markedly higher after experimental navigation and intensive exercise. In Group PNS, the plasma Cort, ACTH and NPY levels decreased significantly compared to Group TC. Meanwhile we found expression levels of pituitary ACTH, NPY also lower than group TC. There was no significant difference about the ultrastructure of anterior pituitary and adrenal cortex of QC and PNS group. However, a obvious change of ultrastructure occurred to TC group rats.

CONCLUSIONThese results suggest that immune-neuroendocrine network function of rats were confused by negative psychological stresses and intensive exercise. PNS therapy may exert regulation effects to the network.

Animals ; Drugs, Chinese Herbal ; administration & dosage ; Exercise ; Humans ; Immune System ; drug effects ; metabolism ; Male ; Models, Animal ; Neurosecretory Systems ; drug effects ; metabolism ; Panax notoginseng ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Saponins ; administration & dosage

In order to explore the influence of psychological stress on the reproductive axis, we started with the original data of biology from animal experiments, then we conducted the factor analysis of 6 important bio-regulatory factors and established the Factor Analysis Model for the endocrine network of reproduction axis under psychological stress. Based on the biological data obtained from animal experiments, it is found that, compared with the relationship seen in the factor analysis model in normal condition, the relationship among the biological factors is more complicated. The key factor, GnRH, has lost its strong regulating action on the subordinate factors, especially on E2; on the other hand, beta-EP has very strong regulating action on E2, and E2 is controlled mainly by beta-EP.
Animals ; Estradiol ; blood ; physiology ; Female ; Follicle Stimulating Hormone ; blood ; physiology ; Gonadotropin-Releasing Hormone ; blood ; physiology ; Models, Biological ; Neurosecretory Systems ; physiology ; Rats ; Reproduction ; physiology ; Stress, Psychological ; metabolism ; physiopathology ; beta-Endorphin ; blood ; physiology

Clinical study of modified Ganmai Dazao decoction in the treatment of yang deficiency climacteric depression and observe the effects of modified Ganmai Dazao decoction on neuroendocrine system in patients with yang deficiency climacteric depression. 86 cases were randomly divided into treatment group treated with modified Ganmai Dazao decoction and control group treated with Deanxit. The curative effect was evaluated with Hamilton's depressive scale (HAMD) and pittsburgh sleep quality scale (PSQI) before and at the end of the two and four weeks of the treatment, the serum levels of serotonin (5-HT), norepinephrine (NE), estradiol (E2), follicle stimulating hormone (FSH), luteotropic hormone (LH) were detected before and after the four weeks of the treatment The results showed that the total effective power of treatment group was 88.4% and the total effective power of control group was 81.4% after four weeks interference, with insignificant difference between the two groups. After two and four weeks of the treatment, the score of HAMD decreased remarkably in both groups (P < 0.01), with insignificant difference between the two groups in same phase. After two and four weeks of the treatment, the total score of PSQI decreased remarkably in both groups (P < 0.05), with significant difference between the two groups after four weeks (P < 0.01). After four weeks of treatment, the serum levels of 5-HT and NE increased (P < 0.01), with insignificant difference between the groups. After four weeks of treatment, the serum levels of E2 increased obviously (P < 0.05), the levels of FSH decreased obviously (P < 0.05), the levels of LH decreased insignificant, with insignificant difference between two groups. This study indicates that modified Ganmai Dazao decoction has obvious therapeutic effects in the treatment of climacteric depression, and showed equivalent efficacy with Deanxit, and modified Ganmai Dazao decoction has better effect on improving the sleep quality in patients than Deanxit, the effect of improved clinical symptoms may be through adjusted levels of 5-HT, NE, E2, FSH and LH of climacteric depression.
Adult ; Depression ; blood ; drug therapy ; etiology ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Follicle Stimulating Hormone ; blood ; Humans ; Menopause ; drug effects ; psychology ; Middle Aged ; Neurosecretory Systems ; drug effects ; metabolism ; Norepinephrine ; blood ; Phytotherapy ; Serotonin ; blood