Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 60-year-old woman was admitted with severe hyponatremia. Basal values of adrenocorticotropic hormone (ACTH), thyroid hormone and cortisol were normal on admission. Impairment of water diuresis was observed by water loading test. Initially, we diagnosed her condition as the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). By provocation test, we finally confirmed that the hyponatremia was caused by hypothalamic adrenal insufficiency. The basal values of ACTH and cortisol might not be sufficient to exclude the possibility of adrenal insufficiency. Therefore, it is necessary to evaluate adrenal function by provocation test or to re-evaluate it after recovery from hyponatremia.
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PMID:Severe hyponatremia caused by hypothalamic adrenal insufficiency. 1039 72

We describe a 51-year-old woman with long-standing young-onset primary hypothyroidism. Serum cortisol, adrenocorticotropin, and arginine vasopressin levels were normal, but urinary excretion of 17-hydroxycorticosteroid was decreased. Administration of a very small initial dose of thyroid hormone induced severe acute complications including fever, palpitation, and sweating associated with a rapid decrease in serum thyrotropin level, a dramatic increase in serum alkaline-phosphatase level, and a decrease in serum total cholesterol level. A week later, the late complications of nausea, severe hyponatremia, and eosinophilia occurred. Serum cortisol level decreased slightly but remained within normal limits during this hyponatremic period. This rare case suggests that increased sensitivity to thyroid hormone can occur in long-standing primary hypothyroidism with biphasic clinical course of acute thyrotoxic complications followed by severe hyponatremia resembling hypoadrenocorticism.
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PMID:Increased sensitivity to thyroid hormone replacement therapy followed by hyponatremia and eosinophilia in a patient with long-standing young-onset primary hypothyroidism. 1043 59

We previously reported that a sex steroid-thyroid hormone (Metharmon-F; MF, 2 tablets daily) was a potent drug for treatment of vitiligo. Using five patients with generalized vitiligo who were successfully treated with oral administration of MF, we performed an immunohistochemical analysis to elucidate its action mechanism at the cellular level. Histopathologically, the repigmented skin after the treatment showed increased numbers of melanocytes and melanin granules. Immunohistochemically, there was little significant difference between the depigmented lesions before treatment and the repigmented lesion after treatment in terms of the reactivity to adrenocorticotropic hormone (ACTH) and alpha-melanocyte-stimulating hormone (alpha-MSH) in keratinocytes. The immunoreactivity to ACTH in melanocytes both before and after the treatment was minimal, but alpha-MSH in melanocytes became much stronger after the treatment, than before the treatment. The efficacy of MF in treatment of vitiligo was proven to be due to the stimulatory effect of melanocyte proliferation and melanin production via alpha-MSH.
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PMID:Immunohistochemical study of ACTH and alpha-MSH in vitiligo patients successfully treated with a sex steroid-thyroid hormone mixture. 1048 4

The hypothalamic arcuate nucleus has an essential role in mediating the homeostatic responses of the thyroid axis to fasting by altering the sensitivity of prothyrotropin-releasing hormone (pro-TRH) gene expression in the paraventricular nucleus (PVN) to feedback regulation by thyroid hormone. Because agouti-related protein (AGRP), a leptin-regulated, arcuate nucleus-derived peptide with alpha-MSH antagonist activity, is contained in axon terminals that terminate on TRH neurons in the PVN, we raised the possibility that alpha-MSH may also participate in the mechanism by which leptin influences pro-TRH gene expression. By double-labeling immunocytochemistry, alpha-MSH-IR axon varicosities were juxtaposed to approximately 70% of pro-TRH neurons in the anterior and periventricular parvocellular subdivisions of the PVN and to 34% of pro-TRH neurons in the medial parvocellular subdivision, establishing synaptic contacts both on the cell soma and dendrites. All pro-TRH neurons receiving contacts by alpha-MSH-containing fibers also were innervated by axons containing AGRP. The intracerebroventricular infusion of 300 ng of alpha-MSH every 6 hr for 3 d prevented fasting-induced suppression of pro-TRH in the PVN but had no effect on AGRP mRNA in the arcuate nucleus. alpha-MSH also increased circulating levels of free thyroxine (T4) 2.5-fold over the levels in fasted controls, but free T4 did not reach the levels in fed controls. These data suggest that alpha-MSH has an important role in the activation of pro-TRH gene expression in hypophysiotropic neurons via either a mono- and/or multisynaptic pathway to the PVN, but factors in addition to alpha-MSH also contribute to the mechanism by which leptin administration restores thyroid hormone levels to normal in fasted animals.
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PMID:alpha-Melanocyte-stimulating hormone is contained in nerve terminals innervating thyrotropin-releasing hormone-synthesizing neurons in the hypothalamic paraventricular nucleus and prevents fasting-induced suppression of prothyrotropin-releasing hormone gene expression. 1066 44

Postnatal handling increases glucocorticoid receptor expression in the rat hippocampus, thus altering the regulation of hypothalamic synthesis of corticotropin-releasing hormone and the hypothalamic-pituitary-adrenal response to stress. The effect on glucocorticoid receptor gene expression represents one mechanism by which the early environment can exert a long-term effect on neural development. The handling effect on hippocampal glucocorticoid receptor expression is dependent on peripheral thyroid hormone release and the activation of ascending serotonergic pathways. In primary hippocampal cell cultures, serotonin (5-HT) increases glucocorticoid receptor expression, and this effect appears to be mediated by increased cAMP levels. In the current studies we examined the in vivo effects of handling on hippocampal cAMP-protein kinase A (PKA) activity. In 7-d-old rat pups, we found that (1) postnatal handling increased adenylyl cyclase activity and hippocampal cAMP levels, (2) the effect of handling on cAMP levels was completely blocked by treatment with either propylthiouracil (PTU), a thyroid hormone synthesis inhibitor, or the 5-HT receptor antagonist, ketanserin, and (3) handling also increased hippocampal PKA activity. We then examined the effects of handling on cAMP-inducible transcription factors. Handling rapidly increased levels of the mRNAs for nerve growth factor-inducible factor A (NGFI-A) (zif268, krox24) and activator protein-2 (AP-2) as well as for NGFI-A and AP-2 immunoreactivity throughout the hippocampus. Finally, we found that the effects of handling on NGFI-A and AP-2 expression were significantly reduced by concurrent treatment with either PTU or ketanserin, effects that paralleled those on cAMP formation. NGFI-A and AP-2 have been implicated in the regulation of glucocorticoid receptor expression during development. Thus, these findings suggest that postnatal handling might alter glucocorticoid receptor gene expression via cAMP-PKA pathways involving the activation of NGFI-A and AP-2.
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PMID:Postnatal handling increases the expression of cAMP-inducible transcription factors in the rat hippocampus: the effects of thyroid hormones and serotonin. 1080 32

A 49-year-old man with herpes simplex encephalitis at age 22 was admitted with hypotension (90/60 mm Hg) and hypothermia (33.7 degrees C). His blood pressure was 80-90/50-60 mm Hg, with temperatures averaging 35 degrees C, for at least 3 years before admission. Evaluation of his hypothermia and hypotension revealed a low free triiodothyronine, low normal thyrotropin, luteinizing hormone < 2 mIU/L, follicle stimulating hormone <3 mIU/L, and low testosterone of 1.39 ng/dL. A baseline cortisol of 13.9 microg/dL was stimulated to 41.8 microg/dL with corticotropin, indicating he had partial anterior hypopituitarism with an intact pituitary-adrenal axis. Posterior pituitary function was normal. MRI revealed a "bright" posterior pituitary on a T1-weighted image, further indicating a normal posterior pituitary. Extensive decreased T1-weighting on MRI in the right and left temporal lobes was consistent with encephalomalacia. With thyroid hormone replacement, his blood pressure increased to 110/70 mm Hg with a temperature of 37 degrees C.
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PMID:Post-herpes encephalitic anterior pituitary insufficiency with hypothermia and hypotension. 1106 53

A chronic minor imbalance between energy intake and energy expenditure may lead to obesity. Both lean and obese subjects eventually reach energy balance and their body weight regulation implies that the adipose tissue mass is "sensed", leading to appropriate responses of energy intake and energy expenditure. The cloning of the ob gene and the identification of its encoded protein, leptin, have provided a system signaling the amount of adipose energy stores to the brain. Leptin, a hormone secreted by fat cells, acts in rodents via hypothalamic receptors to inhibit feeding and increase thermogenesis. A feedback regulatory loop with three distinct steps has been identified: (1) a sensor (leptin production by adipose cells) monitors the size of the adipose tissue mass; (2) hypothalamic centers receive and integrate the intensity of the leptin signal through leptin receptors (LRb); (3) effector systems, including the sympathetic nervous system, control the two main determinants of energy balance-energy intake and energy expenditure. While this feedback regulatory loop is well established in rodents, there are many unsolved questions about its applicability to body weight regulation in humans. The rate of leptin production is related to adiposity, but a large portion of the interindividual variability in plasma leptin concentration is independent of body fatness. Gender is an important factor determining plasma leptin, with women having markedly higher leptin concentrations than men for any given degree of fat mass. The ob mRNA expression is also upregulated by glucocorticoids, whereas stimulation of the sympathetic nervous system results in its inhibition. Furthermore, leptin is not a satiety factor in humans because changes in food intake do not induce short-term increases in plasma leptin levels. After its binding to LRb in the hypothalamus, leptin stimulates a specific signaling cascade that results in the inhibition of several orexigenic neuropeptides, while stimulating several anorexigenic peptides. The orexigenic neuropeptides that are downregulated by leptin are NPY (neuropeptide Y), MCH (melanin-concentrating hormone), orexins, and AGRP (agouti-related peptide). The anorexigenic neuropeptides that are upregulated by leptin are alpha-MSH (alpha-melanocyte-stimulating hormone), which acts on MC4R (melanocortin-4 receptor); CART (cocaine and amphetamine-regulated transcript); and CRH (corticotropin-releasing-hormone). Obese humans have high plasma leptin concentrations related to the size of adipose tissue, but this elevated leptin signal does not induce the expected responses (i.e., a reduction in food intake and an increase in energy expenditure). This suggests that obese humans are resistant to the effects of endogenous leptin. This resistance is also shown by the lack of effect of exogenous leptin administration to induce weight loss in obese patients. The mechanisms that may account for leptin resistance in human obesity include a limitation of the blood-brain-barrier transport system for leptin and an inhibition of the leptin signaling pathways in leptin-responsive hypothalamic neurons. During periods of energy deficit, the fall in leptin plasma levels exceeds the rate at which fat stores are decreased. Reduction of the leptin signal induces several neuroendocrine responses that tend to limit weight loss, such as hunger, food-seeking behavior, and suppression of plasma thyroid hormone levels. Conversely, it is unlikely that leptin has evolved to prevent obesity when plenty of palatable foods are available because the elevated plasma leptin levels resulting from the increased adipose tissue mass do not prevent the development of obesity. In conclusion, in humans, the leptin signaling system appears to be mainly involved in maintenance of adequate energy stores for survival during periods of energy deficit. Its role in the etiology of human obesity is only demonstrated in the very rare situations of absence of the leptin signal (mutations of the leptin gene or of the leptin receptor gene), which produces an internal perception of starvation and results in a chronic stimulation of excessive food intake.
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PMID:Leptin signaling, adiposity, and energy balance. 1207 65

ACTH deficiency gradually develops in patients with growth hormone deficiency (GHD) who have abnormalities of the pituitary stalk on magnetic resonance imaging (MRI) following perinatal complications. We report here a rare case of GHD manifesting ACTH deficiency in middle age. A 48-year-old male patient was admitted to our hospital due to fever and hyponatremia. He was diagnosed as GHD and hypothyroidism at the age of 9, and had received lysine treatment until age 20, which was then replaced by thyroid hormone. He was not mentally retarded, but was the shortest in his class throughout his schooldays, reaching a final height of 148 cm. Hormonal examination revealed the presence of hypoadrenalism as indicated by poor responses of plasma cortisol to intravenous administration of corticotropin-releasing hormone (CRH) and insulin-induced hypoglycemia. Plasma ACTH responded well to CRH, but not to insulin-induced hypoglycemia, indicating that his hypoadrenalism was of hypothalamic origin. MRI showed an invisible pituitary stalk and relatively small pituitary gland. Since he had a perinatal abnormality, the damage around the pituitary and GHD could have originated from birth. In the literature, around 60% of GHD patients with pituitary stalk abnormalities develop hypoadrenalism due to ACTH deficiency, and more than 90% of such cases are diagnosed by age 30. We suggest that the appearance of hypoadrenalism should be carefully monitored in GHD patients with pituitary stalk abnormalities even after they reach middle age.
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PMID:Late onset of adrenocortical failure in GH deficiency with invisible pituitary stalk: a case report of a 48-year-old Japanese man and review of the literature. 1208 Dec 44

We analyzed data from 65 children with septo-optic dysplasia (SOD) referred for evaluation and followed in the National Cooperative Growth Study (NCGS) Substudy 8 and from 758 children treated with growth hormone (GH) and followed in the NCGS core study. Compared to other children referred for evaluation of short stature, children with SOD were younger (mean age 3.7 +/- 3.6 vs 8.6 +/- 4.9 years), had less severe short stature (mean +/- SD height SDS -1.80 +/- 1.64 vs -2.17 +/- 0.95), and were more likely to be female (46% F vs 31% M). Children with SOD who received GH were older and shorter than those referred and untreated, but the gender distribution was similar. Other pituitary hormone deficits were reported in untreated patients, including thyroid hormone deficiencies (8%) and adrenocorticotropic hormone (ACTH) deficiency (3%), as compared to 27% and 24%, respectively, in GH-treated children. Data on adult height were available for 71 patients, who showed an average gain in height SDS of 1.17 +/- 1.49. GH therapy was well tolerated in children with SOD.
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PMID:Septo-optic dysplasia/optic nerve hypoplasia: data from the National Cooperative Growth Study (NCGS). 1209 83

Because alpha-MSH has a potent stimulatory action on hypophysiotropic TRH synthesizing neurons in the hypothalamic paraventricular nucleus (PVN), preventing the effects of fasting on the gene expression of the TRH prohormone (proTRH), we hypothesized that agouti-related protein (AGRP), a melanocortin receptor antagonist, may exert a central inhibitory action on these neurons. To test the hypothesis, the effects of intracerebroventricularly administered AGRP on circulating thyroid hormone levels and proTRH mRNA in the hypothalamic paraventricular nucleus (PVN) were compared with the effects of the recently described central inhibitor of the HPT axis, neuropeptide Y (NPY). AGRP administration increased food consumption and weight gain, suppressed circulating levels of thyroid hormones (T(3) and T(4)), and resulted in an inappropriately normal TSH. These alterations were associated with a significant suppression of proTRH mRNA in the PVN, indicating that AGRP infusion resulted in a state of central hypothyroidism. While similar observations were made in the NPY-infused animals, AGRP-treated animals had higher feeding efficiency, higher T(4) levels, and lower type 2 iodothyronine deiodinase levels in brown adipose tissue than NPY-infused animals. These data demonstrate that AGRP and NPY have a similarly potent inhibitory action on the proTRH gene expression of hypophysiotropic neurons, indicating that both AGRP and NPY may play a major role in the inhibition of the HPT axis during fasting.
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PMID:Agouti-related protein (AGRP) has a central inhibitory action on the hypothalamic-pituitary-thyroid (HPT) axis; comparisons between the effect of AGRP and neuropeptide Y on energy homeostasis and the HPT axis. 1223 96


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