BACKGROUND: It has been already known that each trophic hormone in combined pituitary responsiveness according to gender and age brings about variable response, but in Korea, there has been no actual data. In this study, in order to assess the pituitary responsiveness, a combined pituitary stimulation test was performed in Korean subjects with the variation in CRH, GHRH, GnRH, and TRH according to their age and gender. Were these the variables that were changed according to age and gender? Clarify that. Also, it might be good to write out the abbreviations.) METHOD: Fourteen physically and mentally healthy male subjects and fourteen female subjects, also physically and mentally healthy, underwent the combined anterior pituitary stimulation test by CRH, GHRH, LHRH, and TRH. Each gender group was divided further into young(meanSE; male: 231, female: 221) and old (mean; male: 513, female: 522) groups. RESULTS: There were significant differences between the gender and age groups. The Peak GH level and maximal GH increment were significantly increased in young men compared to old men. The Peak ACTH level and maximal ACTH increment were significantly increased in old men as opposed to young men. The Peak PRL level, maximal PRL increment, Peak TSH level, and maximal TSH increment were significantly increased in old women compared to old men. The Peak FSH level was significantly increased in the two old groups compared to the young groups, which showedindependence in gender, and the maximal FSH increment was significantly increased in old men when compared with the young men. CONCLUSION: These results show that in order to for accurate interpretation of the response from the combined pituitary stimulation test, it is necessary to consider age and gender of the subjects. We suggest response values of the combined pituitary stimulation test in terms of age and gender in healthy Korean subjects.
Adrenocorticotropic Hormone ; Corticotropin-Releasing Hormone ; Female ; Gonadotropin-Releasing Hormone* ; Growth Hormone-Releasing Hormone ; Humans* ; Korea ; Male

OBJECTIVETo investigate the effect of preventive moxibustion at the acupoint of 'Guanyuan" (CV 4) on the stress-related hormones, proteins and genes in natural menopausal rats, and explore its protective mechanism.

METHODSOne hundred and twenty eight healthy female SD rats were used in this study, in which 16 rats aged 4 months were used as normal control group, the rest 10-month-old rats with disorder of estrus cycle were randomly divided into 7 groups, including 4 control groups at the age of 10, 12, 14 and 16 months, and 3 preventive moxibustion groups at the age of 12, 14 and 16 months, 16 cases in each group. The 10-month-old rats were treated with preventive moxibustion at the acupoint of "Guanyuan" (CV 4), twice a week for 8 weeks consistently, then observed on the following 12, 14 and 16 months. Its effects on the level of heat shock protein 70 (HSP 70), heat shock protein 70 mRNA (HSP 70 mRNA), corticotropin-releasing hormone (CRH), beta-endorphin (beta-EP), adrenocorticotrophic hormone (ACTH) in the different nuclei of hypothalamus were examined with radio-immunity, immunohistochemistry or in situ hybridization methods.

RESULTSIn the control groups, the expression of HSP 70 and HSP 70 mRNA was increased in paraventricular, arcuate and supraoptic nucleus, the level of CRH, beta-EP was showed with declining trend in volatility, while the content of ACTH was increased. In comparison to the same-aged control groups, the preventive moxibustion groups were showed that the expression of HSP 70 in the 14-month-old group was lower and the expression of HSP 70 mRNA in the 12 and 16-month-old group was significantly higher in the paraventricular nucleus (all P < 0.05), the expression of HSP 70 in the 12 and 14-month-old groups and HSP 70 mRNA in the 12-month-old group was significantly increased in the arcuate nucleus (P < 0.05, P < 0.01), while the expression of HSP 70 in the 14-month-old group and HSP 70 mRNA in the 12 and 16-month-old group was significantly decreased in the supraoptic nucleus (all P < 0.05), the content of CRH and ACTH decreased significantly in 14-month group (P < 0.05, P < 0.01), but the content of beta-EP obviously went up in the 12-month-old group (P < 0.05).

CONCLUSIONPreventive moxibustion at the acupoint of "Guanyuan" (CV 4) can regulate the expression of stress proteins, genes and hormones in the hypothalamus for the natural menopausal rats, which might be playing a protective role.

Adrenocorticotropic Hormone ; metabolism ; Animals ; Corticotropin-Releasing Hormone ; metabolism ; Female ; Heat-Shock Proteins ; genetics ; metabolism ; Humans ; Hypothalamic Hormones ; metabolism ; Menopause ; genetics ; metabolism ; Models, Animal ; Moxibustion ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; beta-Endorphin ; metabolism

To classify the causes of hypogonadotropic hypogonadism in Korean patients, and to improve the endocrinologic evaluation for the disease, we retrospectively studied the clinical findings and result of combined pituitary stimulation test in 35 patients with hypogonadotropic hypogonadism. The following results were obtained.1) The ratio of male to female was 1.3:1, and the 50% of male patients was under 20 years of age and the 20% of female patients in 30th decades. 2) The chief complaints of male patients on the admission were the failure of secondary sexual characteristics(95.0%) and loss of hair(5.0%), those of female patients were amenorrhea(46.7%), infertility(26.7%), failure of secondary characteristics(13.3%) and loss of hair(13.3%). 3) The causes of male hypogonadotropic hypogonadism were craniopharyngioma(35.0%), idiopathic(30.0%), Kallmann's syndrome(15.0%), pituitary adenoma(10.0%) and germinoma(5.0%), and those of female hypogonadotropic hypogonadism were prolactinoma(13.3%), Sheehan's syndrome(26.6%), pituitary adenoma(6.7%), tuberculous granuloma(6.7%), germinoma(6.7%), idiopathic hypogonadotropic hypogonadism(40.0%).4) The responses of LH and FSH to GnRH test were absent or markedly blunted in diffuse pituitary diseases such as pituitary tuberculous granuloma, pituitary macroadenomas, Sheehan's syndrome. However those were also absent or blunted in Cushing's disease and hypothalamic disease such as Kallmann's syndrome, germinoma, craniopharyngioma, idiopathic hypogonadotropic hypogonadism. 5) The responses of LH, FSH increased after repeated injection of GnRH in a patient with germinoma. 6) In diffuse destructive pituitary diseases such as Sheehan's syndrome, nonfunctioning macroadenomas, tuberculous granuloma, large prolactinoma, the combined deficiency of pituitary hormones other than gonadotropins was observed. 7) In many cases with hypothalamic diseases, the combined defects of pituitary hormone response were also seen.These data suggest that GnRH test is not always useful to localize the lesion between pituitary and hypothalamus, and combined pituitary stimulation test revealed defects of pituitary hormones other than gonadotropin in various hypothalamic diseases.Therefore repeated GnRH test would be useful for the differential diagnosis, and CRH test and GRH test would be necessary to demonstrate whether pituitary abnormality is present.
Craniopharyngioma ; Diagnosis, Differential ; Female ; Germinoma ; Gonadotropin-Releasing Hormone ; Gonadotropins ; Granuloma ; Humans ; Hypogonadism ; Hypopituitarism ; Hypothalamic Diseases ; Hypothalamus ; Kallmann Syndrome ; Male ; Pituitary Diseases ; Pituitary Hormones ; Prolactinoma ; Retrospective Studies

OBJECTIVES: Corticotropin releasing factor (CRF) plays a primary role in coordinating the neuroendocrine, autonomic, immune and behavioral responses to stress. CRF exerts its action through two major receptors, corticotropin-releasing factor 1 Receptor (CRF-R1) and corticotropin-releasing factor 2 receptor (CRF-R2). Using two types of chronic stress models, we investigated the changes of CRF-R1 mRNA and CRF-R2A mRNA expressions and CRF mRNA in the stress related brain circuit areas. METHODS: Male Sprague-Dawley rats were exposed to either immobilization stress or variable intermittent unpredictable stress for 10 days and then in situ hybridization histochemistry was used to quantify CRF expression in the brain. RESULTS: 1) CRF1 receptor mRNA expressions were decreased in bed nucleus stria terminalis (BNST) following stressors. 2) CRF2A receptor mRNA expressions were increased in lateral septum following stressors. 3) CRF mRNA expressions were increased in central nucleus of amygdala (CeA) and BNST. CONCLUSION: The increased CRF mRNA of CeA and BNST may be related with anxiety response in the repeated stress. Down-regulation of CRF-R1 mRNA expression in BNST may represent a compensatory adaptation to chronic stress and may be involved in the anxiety response, whereas up-regulation of CRF-R2A mRNA expression in lateral septum may represent an anxiety response or impaired learning but the functional meaning is uncertain.
Adrenocorticotropic Hormone* ; Amygdala ; Anxiety ; Brain ; Corticotropin-Releasing Hormone* ; Down-Regulation ; Humans ; Immobilization ; In Situ Hybridization ; Learning ; Male ; Rats, Sprague-Dawley ; Receptors, Corticotropin-Releasing Hormone ; RNA, Messenger ; Up-Regulation

PURPOSE: The purpose of this study was to investigate the clinical and hormonal features of patients with incidentally discovered adrenal adenomas in relation to corticotropin releasing hormone (CRH) testing and the clinical outcome of adrenalectomy. MATERIALS AND METHODS: Twenty-three consecutive patients with incidentally detected adrenal adenomas were included in this retrospective study. All the patients underwent abdominal computed tomography scans and hormonal assays, including assessment of circadian rhythms of plasma cortisol and corticotropin (adrenocorticotropic hormone, ACTH), a corticotropin stimulation test, and low-dose and high-dose dexamethasone tests. The patients were reevaluated at regular intervals (6, 12, and 24 months) for a median period of 24 months. Subclinical Cushing's syndrome (SCS) was diagnosed in patients with subtle hypercortisolism who did not present clinical signs of Cushing's syndrome. RESULTS: We calculated the responsive index (peak value of ACTH in CRH test/baseline value of ACTH in CRH test). Of 23 patients, 6 had Cushing's syndrome, 8 had SCS, and 9 had a non-functioning tumor. All patients underwent laparoscopic adrenalectomy. Several patients (5 of 6 with Cushing's syndrome and 2 of 8 with SCS) required cortisol replacement therapy after surgery. The remaining patients required no hormonal replacement after surgery. Those who required hormone replacement had a responsive index of less than 1.2. Those who did not need hormone replacement therapy had a responsive index of more than 2.0. CONCLUSIONS: In our limited experience, the responsive index of the CRH test might be a valuable tool for predicting the need for cortisol replacement after surgery in patients with SCS.
Adenoma ; Adrenalectomy ; Adrenocorticotropic Hormone ; Circadian Rhythm ; Corticotropin-Releasing Hormone ; Cushing Syndrome ; Dexamethasone ; Hormone Replacement Therapy ; Humans ; Hydrocortisone ; Plasma ; Retrospective Studies

Human placenta synthesizes bioactive corticotropin releasing factor(CRF), a 41 amino acid peptide, which displays identical immunological, biological, and chemical characteristics to hypothalamic CRF. Placental CRF enters the maternal circulation and stimulates release of local placental prostaglandin E2 and F2alpha that have a central role in the mechanisms controlling uterine contractility and cervical softening. A large number of clinical investigators has suggested that placental CRF may be involved in mechanisms leading to labor. As well as CRF`s rises in term pregnancy, maternal serum CRF levels are also elevated in pregnancies complicated by preterm labor. So the clinical use of maternal serum CRF levels as a predictor of preterm labor was proposed. Therefore, we have carried out a prospective study on the efficacy of maternal serum CRF levels in diagnosis of preterm labor. In this study, the subjects consisted of 30 women admitted for the treatment of preterm labor and another 30 women with normal pregnancies between 28 and 36 completed weeks of gestation, and their serum CRF levels were assessed. The results were as follows: 1. In both groups, serum CRF levels were increased as being associated to gestational ages, especially in late pregnancy. 2. In a comparative study between two groups, the serum CRF values of pregnancies complicated by preterm labor were significantly higher than their values of control group(p<0.05). 3. In pregnancies complicated by preterm labor, the serum CRF values of preterm delivery were not significantly elevated comparing with their values of other pregnancies complicated bypreterm labor(p>0.05).
Adrenocorticotropic Hormone* ; Corticotropin-Releasing Hormone* ; Diagnosis* ; Dinoprostone ; Female ; Gestational Age ; Humans ; Obstetric Labor, Premature* ; Placenta ; Pregnancy* ; Prospective Studies ; Research Personnel

Drugs of abuse leads to adaptive changes in the brain stress system, and produces negative affective states including aversion and anxiety after drug use is terminated. Corticotrophin-releasing hormone (CRH) is the main transmitter in control of response to stressors and is neuronal enriched in the central amygdala (CeA), a sub-region of the extended amygdala playing an important role in integrating emotional information and modulating stress response. The effect of CRH neurons in CeA on the negative emotions on morphine naïve and withdrawal mice is unclear. Thus, we utilized CRH-Cre transgenic mice injected with AAV-mediated Designer Receptors Exclusively Activated By Designer Drugs (DREADDs) to chemogenetically manipulate CRH neurons in CeA. And methods of behavior analysis, including conditioned place aversion (CPA), elevated plus maze and locomotor activity tests, were used to investigate morphine withdrawal-induced negative emotions in mice. The results showed that, inhibiting CRH neurons of CeA decreased the formation of morphine withdrawal-induced CPA, as well as the anxiety level of CRH-Cre mice. Furthermore, specifically activating CRH neurons in CeA evoked CPA and anxiety of morphine naïve mice. Neither inhibiting nor activating CRH neurons had effects on their locomotor activity. These results suggest that CRH neurons in CeA are involved in the mediation of morphine withdrawal-induced negative emotion in mice, providing a theoretical basis for drug addiction and relapse mechanism.
Adrenocorticotropic Hormone ; Animals ; Central Amygdaloid Nucleus ; Corticotropin-Releasing Hormone ; metabolism ; Emotions ; physiology ; Mice ; Morphine ; metabolism ; Neurons ; metabolism

Isolated ACTH deficiency is a rare cause of secondary adrenocortical insufficiency. Adrenal crisis in isolated ACTH deficiency is less common compared to primary adrenal insufficiency, but isolated ACTH deficiency is an important cause of hypoglycemia. Recently we experienced a 41-year-old man admitted because of mental confusion. On admission, plasma glucose and sodium concentration were 1.7, 132 mmol/L, respectively. Basal plasma ACTH and cortisol levels were low and other pituitary hormone showed normal response to combined pituitary stimulation test except growth hormone. Plasma ACTH concentration remained low even after intravenous injection of ovine corticotropin releasing factor. It suggest that the defect of ACTH secretion was apparently due to intrinsic pituitary rather than hypothalamic disease. The sellar CT showed the fossa to be filled by cerebrospinal fluid. After treatment with glucocorticoid, he had no further evidence of hypoglycemia and hyponatremia. In conclusion, we report a case of isolated ACTH deficiency with empty sella.
Addison Disease ; Adrenocorticotropic Hormone ; Adult ; Blood Glucose ; Cerebrospinal Fluid ; Corticotropin-Releasing Hormone ; Growth Hormone ; Humans ; Hydrocortisone ; Hypoglycemia ; Hyponatremia ; Hypothalamic Diseases ; Injections, Intravenous ; Plasma ; Sodium

BACKGROUND: Rapid adrenocorticotropin (ACTH) stimulation test using 250ug of ACTH (1-24) has been used as a standard test in the initial assessment of adrenal function. However, it has recently been suggested that a rnaximal cortisol response can be achieved with a much lower ACTH dose, and reducing the dose might further enhance the sensitivity of the test in the detection of mild adrenal insufficiency. This study was performed to evaluate the role of low-dose (lug) ACTH stimulation test in the assessment of adrenal function and the diagnosis of subtle adrenal insufficiency. METHODS: Twenty-two subjects with suspected adrenal insufficiency due to long-term corticosteroid use were included in this study. The correlations between clinical features and the serum cortisol responses to low dose (lug) and high dose (250 ug) ACTH stimulation were evaluated. RESULTS: In high dose test, 10 (67%) out of 15 subjects with clinical features of adrenal insufficiency showed decreased serum cortisol response (peak cortisol level <18 ug/dL), but 5 (33%) subjects showed normal response (peak cortisol level > 18ug/dL). On the other hand, 14 (93%) subjects with clinical features of adrenal insufficiency showed decreased serum cortisol response in low dose test, while only one showed normal response. In 7 subjects without clinical features of adrenal insufficiency, 5 subject (71%) showed normal response, and 2 subjects (29%) showed decreased response in both low and high dose tests. CONCLUSION: These results suggest that the 1-ug low dose ACTH stimulation test might be more sensitive than conventional 250-ug test in the detection of mild adrenal insufficiency. Further studies are needed to determine the optimal dose of ACTH and the criteria for normal response to ACTH stimulation.
Adrenal Insufficiency* ; Adrenocorticotropic Hormone* ; Cosyntropin ; Diagnosis* ; Hand ; Hydrocortisone

OBJECTIVETo explore the protection of high intensity microwave radiation on hypothalamo-pituitary-adrenal axis (HPAA) activity and hippocampal CA1 structure in rats and the protectiveeffect of Qindan Granule (QG) on radiation injured rats.

METHODSTotally 48 Wistar rats were randomlydivided into 8 groups, i.e., the normal control group, post-radiation day 1, 7, and 10 groups, 7 and 10days prevention groups, day 7 and 10 treatment groups, 6 in each group. Rats in prevention groups wererespectively administered with QG liquid (1 mL/100 g, 4. 75 g crude drugs) for 7 days and 10 days bygastrogavage and then microwave radiation. Then preventive effect for radiation injury was statisticallycalculated with the normal control group and the post-radiation day 1 group. Rats in treatment groupswere firstly irradiated, and then administered with QG liquid (1 mL/100 g, 4.75 g crude drugs). Finally preventive effect for radiation injury was statistically calculated with the normal control group, post-radiation day 7 and 10 groups. Contents of corticotrophin releasing hormone (CRH), beta endorphin (beta-EP), adrenocorticotropic hormone (ACTH), and heat shock protein 70 (HSP70) were detected. Morphological changes and structure of hippocampal CA1 region were observed under light microscope.

RESULTSCompared with the normal control group, contents of CRH and beta-EP significantly decreased in each radiation group. Serum contents of ACTH and beta-EP significantly increased in post-radiation day 1 and 7 groups (P < 0.05). Compared with radiation groups, beta-EP content in serum and pituitary significantly increased, and serum ACTH content significantly decreased in prevention groups (P < 0.05). Pituitary contents of CRH and beta-EP significantly increased in prevention groups. Serum contents of ACTH, beta-EP, and HSP70 were significantly lower in day 7 treatment group than post-radiation day 7 group (P < 0.05). Morphological results showed that pyramidal neurons in the hippocampal CA1 region arranged in disorder, with swollen cells, shrunken and condensed nucleus, dark dyeing cytoplasm, unclear structure. Vessels in partial regions were dilated with static blood; tissues were swollen and sparse. In prevention and treatment groups pathological damage of hippocampal CA1 region was obviously attenuated; neurons were arranged more regularly; swollen, pycnotic, or deleted neuron number were decreased; vascular dilatation and congestion was lessened.

CONCLUSIONQG could affect HPAA function and activity of high intensity microwave radiated rats, showing certain preventive and therapeutic effects of microwave radiated rats by adjusting synthesis and release of partial bioactive peptides and hormones in HPAA, improving pathological injury in hippocampal CA1 region.

Adrenocorticotropic Hormone ; blood ; Animals ; CA1 Region, Hippocampal ; drug effects ; pathology ; radiation effects ; Corticotropin-Releasing Hormone ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; HSP70 Heat-Shock Proteins ; blood ; Hypothalamo-Hypophyseal System ; drug effects ; radiation effects ; Microwaves ; adverse effects ; Pituitary-Adrenal System ; drug effects ; radiation effects ; Random Allocation ; Rats ; Rats, Wistar ; beta-Endorphin ; blood ; metabolism