Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The reaction products of plasma enzyme degradation of TRH were identified by thin layer chromatography. The enzyme in normal rat plasma yields proline and pGlu-His as major reaction products. High concentrations of proline decrease peptide cleavage, resulting in greater amounts of acid TRH. The apparent Km of the enzyme is 4.1 X 10(-6) M. LHRH and neurotensin are competitive inhibitors with Ki of 5 X 10(-6) M and 1.5 X 10(-5) M, respectively. Somatostatin, MIF, oxytocin, arg-vasopressin, arg-vasotocin, neurophysin II and glucagon do not compete; and pGlu-His-Pro-OH, Glu-His-Pro-OH, pGlu-His, His-Pro-NH2, and Pro-NH2 do not affect enzyme activity. These data suggest that the substrated requires pGlu and a terminal or internal amide to complex with the enzyme. The enzyme is markedly inhibited by Cu++, Bal, benzamadine, p-(chloromercuri)-benzoic acid, moderately affected by EDTA and puromycin, and unaffected by mercaptoethanol. TSH does not affect enzyme activity while LH inhibits it moderately at high concentrations (300-600 pg/ml).
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PMID:Characteristics of the plasma TRH-degrading enzyme. 81 19

The changes in plasma thyroid hormone concentration were studied during exchange transfusion performed for haemolytic disease. 24 transfusions were performed using blood preserved with acid-citrate and dextrose and in 11 cases 10 or 50 mug glucagon was added to the donor blood. Plasma tri-iodothyronine (T3), thyroxine (T4), thyrotropin (TSH), thyroid hormone binding capacity, and free thyroxine index were measured in the donor blood and in the infant at the start and at intervals during the transfusion. Before transfusion the plasma TSH levels of the infants fell as postnatal age indreased and plasma T3 and T4 were correlated with one another. In 20 transfusions the mean infant/donor ratio of TSH was approximately 10, of T4 3, and of T3 2. During these transfusions there was a progressive fall in the infant's plasms TSH, T4, and T3 concentration. In 3 transfusions in which the donor plasma TSH was greater than that of the infant, plasma TSH levels rose during the transfusion and in 2 cases this was associated with a late rise in plasma T3 levels. The addition of glucagon to donor blood had no effect on thyroid hormone levels. It is concluded that erythroblastotic infants have normal thyroid function and that they became biochemically hypothyroid during transfusion. Acute changes in plasma thyroid hormone and glucagon concentration do not induce TSH responses by the neonatal pituitary during the period of the exchange transfusion.
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PMID:Thyroid function during exchange transfusion. 116 47

The association of hypoglycemia and microphallus in the male neonate is presumptive evidence of congenital hypopituitarism. This was observed in four male infants with normal birth weight and length, optic discs, and intelligence, and without gross central nervous system malformations. Plasma and urinary cortisol values were low. Stimulation with metyrapone and insulin hypoglycemia failed to elicit a rise in plasma corticoids, but multiple doses of ACTH evoked a response. Growth hormone responses to arginine, insulin, sleep, L-dopa, and glucagon were uniformly less than 2.5 ng/ml. In three patients, however, length remained within 2 SD of the mean until two years of age; in one, there was a sharp decrease in growth by three months. Two patients had low plasma TSH and thyroxine concentrations within the first month of life. In the other two patients, whose thyroxine levels were measurable, intravenous administration of thyrotropin-releasing factor evoked a normal rise in plasma TSH; serum thyroxine decreased into the hypothyroid range in one after GH therapy was initiated. Plasma prolactin was normal in the first two patients receiving thyroxine replacement therapy. The other two patients had elevated baseline prolactin levels and had an augmented rise in plasma prolactin after administration of TRF. Human chorionic gonadotropin induced a 10- to 15-fold rise in plasma testosterone in the two patients tested. The changes in plasma FSH and LH after luteinizing hormone-releasing factor were either low or in the prepubertal range. In three patients, treated with testosterone enanthate intramuscularly, phallic growth occurred. In addition, all three had a transient increase in height but no acceleration of skeletal maturation. The data suggest a deficiency of hypothalamic hypophysiotropic hormones rather than a primary pituitary defect. Early recognition of this syndrome complex is critical for prompt treatment of the life-threatening cortisol deficiency. The diagnosis is more difficult in affected females because their external genitals are normal. The microphallus is a remediable manifestation of hypopituitarism.
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PMID:Congenital hypopituitarism associated with neonatal hypoglycemia and microphallus: four cases secondary to hypothalamic hormone deficiencies. 118 16

Somatostatin, a peptide isolated from ovine hypothalami, prevents growth hormone secretion in vivo and in vitro. Moreover, somatostatin interferes with the secretion of various other hormones: TSH insulin, glucagon, gastrin, VIP and GIP. Under certain conditions a blunting effect on the secretion of prolactin and ACTH can be demonstrated.
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PMID:[Somatostatin -- a review (author's transl)]. 126 5

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 38-amino acid peptide of the glucagon-secretin-vasoactive intestinal polypeptide superfamily. Although PACAP is a potent stimulator of adenylate cyclase activity in the adenohypophysis, the precise target cells for PACAP in the anterior pituitary remain unknown. The aim of the present study was to investigate whether PACAP could stimulate calcium mobilization in individual cells of the pituitary and to determine the type of cells that responded to PACAP. Enzymatically dispersed frog distal pituitary cells were plated on photoetched coverslips and cultured for 3-7 days. The cells were loaded with the fluorescent calcium indicator indo-1, and changes in intracellular calcium concentrations ([Ca2+]i) were monitored using dual wavelength microfluorimetry. The individual cells were localized with the aid of the alpha/numeric grid of the coverslips and identified retrospectively by immunofluorescence. Approximately 45% of GH and PRL cells and 25% of ACTH and TSH cells responded to PACAP (10(-5) M) ejection by an elevation of [Ca2+]i. Only 16% of gonadotropes were stimulated by PACAP. The time course of [Ca2+]i variations showed three different patterns: transient spikes, sustained stimulations, and oscillatory responses. In addition, heterogenous responses were observed within each cell type. These data provide evidence for the involvement of calcium mobilization in the mechanism of action of PACAP on pituitary cells. The results also indicate that in frogs, PACAP may stimulate the secretory activity of GH and PRL cells and, to a lesser extent, ACTH, TSH, and gonadotrope cells.
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PMID:Pituitary adenylate cyclase-activating polypeptide stimulates calcium mobilization in amphibian pituitary cells. 132 48

Two hundred and forty-one cases of isolated ACTH deficiency have been reported in Japan since 1969. Pituitary hormone responsiveness to stimulation tests before and after hydrocortisone supplementation was investigated in these cases. Plasma ACTH level showed no or little change in response to lysine vasopressin, metyrapone, CRF or insulin-induced hypoglycemia in 97.3-100% of the cases. Serum GH level changed little or not at all in response to GRF, insulin-induced hypoglycemia, glucagon, 1-dopa and arginine in 26.9, 29.3, 40.0, 50.0 and 56.1%, respectively. Serum TSH and prolactin (PRL) levels showed hyperresponse to TRH in 34.7 and 35.6%, respectively. After hydrocortisone therapy, GH secretion was more responsive than before therapy in 78.9% of the cases. After supplementation, TSH level was less responsive to TRH stimulation than before therapy in 59.3% of the cases. After hydrocortisone supplementation, TSH response to TRH decreased in 75% of ACTH-deficient patients without primary hypothyroidism but did not decrease in more than half of those with primary hypothyroidism. TSH response to TRH decreased after supplementation in 76.5% of the patients with TSH hyperresponsiveness before therapy, and increased after therapy in 66.7% of those with normal TSH responses before therapy. After supplementation, PRL response to TRH was less than that before therapy in 43.5% of ACTH--deficient patients, and greater than that before therapy in 30.4%. PRL response to TRH decreased after therapy in 66.7% of the patients with PRL hyperresponsiveness before therapy, and increased in 63.6% of those with normal PRL response before therapy. Primary hypothyroidism and Hashimoto's thyroiditis were complicated in 21.6 and 11.6%, respectively, of the 241 patients with isolated ACTH deficiency. In patients who had TSH hyperresponsiveness and/or high basal TSH levels and PRL hyperresponsiveness and/or high basal PRL levels, primary hypothyroidism was complicated in 58.4 and 42.3%, respectively. Hashimoto's thyroiditis was complicated in 29.8 and 20.5%, respectively, of these patients. Pituitary cell antibody (PCA) was detected in 36.6% of ACTH-deficient patients who were examined. Pituitary cell surface antibody (PCSA) to AtT-20 cells and GH3 cells was detected in 50.0 and 28.0% of the examined cases, respectively. The prevalence of PCA and PCSA did not differ between TSH-hyperresponsive patients and those with normal TSH basal levels and response, whereas PCA and PCSA were significantly more prevalent in PRL-hyperresponsive patients than in those with normal PRL levels and response. An empty sella was found in 30.2% of the examined case.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Hyperresponsiveness of TSH and prolactin and impaired responsiveness of GH in Japanese patients with isolated ACTH deficiency]. 133 97

The SRIF analog octreotide (SMS 201-995) has been in clinical use for over 6 yr in the treatment of acromegaly and metastatic endocrine pancreatic and carcinoid tumors. The use of the analog in the treatment of acromegaly and TSH-secreting tumors is beyond the scope of this clinical review. Patient acceptance of the analog, given chronically by the sc route, has been excellent and side effects have been few with the exception of the development of gallstones. In endocrine pancreatic and carcinoid tumors the hypersecretion of hormones such as VIP, glucagon, and gastrin and the secretory products of carcinoid tumors (e.g. 5-hydroxytryptamine and tachykinins) and their clinical effects may be successfully blocked. This allows excellent palliation of such tumors and often enables the patients to return home and lead normal social lives. Initial hopes that long-term octreotide therapy would be an effective antitumor drug, reducing tumor growth, based on experimental animal models and human tumor cell lines, have not been born out in clinical practice. A reduction in gut tumor bulk due to octreotide, rarely or never occurs as a sustained phenomenon. Eventually a decrease in, and finally an absence of, clinical effectiveness occurs despite the reintroduction of other treatment modalities.
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PMID:Clinical review 23: The use of the long-acting somatostatin analog octreotide in the treatment of gut neuroendocrine tumors. 164 13

Fasting blood samples were collected from 83 patients with histologically proven breast cancer and analysed for plasma glucagon, serum immunoreactive tumour necrosis factor (TNF alpha), insulin, glucose, growth hormone, cortisol and TSH. Samples from patients with known diabetes mellitus or thyroid disease, and those on parenteral nutrition or with evidence of infection were excluded as were patients who had a history of weight loss through dieting or who were anorexic. Fasting plasma glucagon, serum cortisol and immunoreactive TNF alpha concentrations in patients with stage IV breast cancer who had developed weight loss were significantly higher than those in patients with stage IV disease who had not developed weight loss. There were no significant differences in the fasting serum concentrations of insulin, glucose, growth hormone and TSH between the two patient groups. The association between weight loss in stage IV breast cancer and increased concentrations of plasma glucagon, serum cortisol and TNF alpha suggests a possible role for these hormonal factors in the development of cancer cachexia.
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PMID:Hormonal factors associated with weight loss in patients with advanced breast cancer. 195 51

In order to establish the extent of neuroendocrine differentiation and the occurrence of neurohormonal peptides in the neoplastic cells of prostatic carcinomas, silver-staining and immunocytochemical techniques were used. All gave satisfactory results. The incidence of the neuroendocrine cells seemed to be higher in the fresh "Bouin-fixed" biopsy specimens than in the conventionally "formalin-fixed" specimens from archival paraffin blocks. All carcinomas demonstrated argyrophil cells as an integral element of the tumour. In highly differentiated carcinomas (grade I) these cells were scattered focally, intermingled with non-argyrophil cells in typical adenocarcinomas; their incidence was estimated to be about the same as in benign prostatic hyperplasia. Most of them were immunoreactive with antisera raised against serotonin and/or TSH (thyroid stimulating hormone). In moderately and poorly differentiated (grades II-III) carcinomas, however, the argyrophil cells were more numerous and showed greater variation in growth pattern; only occasionally they displayed a typical carcinoid-like structure. Moderately and poorly differentiated carcinomas also showed a greater variation in the number and kinds of peptide immunoreactivities than the highly differentiated carcinomas. In addition to serotonin- and TSH-immunoreactive cells as the most prevalent type, now also human chorionic gonadotrophin (HCG-alpha), adrenocorticotropic hormone (ACTH), leu-enkephalin, beta-endorphin, somatostatin, glucagon and calcitonin immunoreactive cells could be found within certain tumour areas and often with a distinctly patchy distribution. In two cases, where the tumour cells in the metastases were also investigated, they were found to be both argyrophil and immunoreactive with the same antisera as those of the primary tumour. Our findings emphasise the fact that prostatic carcinomas are more complex and heterogenous than previously thought, exhibiting endocrine differentiation as an integral element of virtually all prostatic adenocarcinomas.
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PMID:Peptide-hormone- and serotonin-immunoreactive tumour cells in carcinoma of the prostate. 244 32

After burn trauma, a very marked endocrine response occurs. Almost all the known hormones take part in it. Their response influences very much the postburn metabolic changes and participates in the integration of the body's response with the nervous and immune systems. In this review, mainly the changes in various hormone levels are described, as well as the possible role of the acute phase response after burn trauma, and the communications between the endocrine and immune systems, the cells of the latter are able to respond to various hormonal stimuli and to secrete various hormones themselves. Some of the hormones are very sensitive indicators of the burn stress, e.g., the T3 levels (very low), testosterone in males (very low), dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) (very low), ADH, catecholamines, renin and angiotensin II, cortisol (high), 17-beta-estradiol in males (usually elevated). Other hormones are usually elevated, but not always (ACTH, aldosterone, prolactin, glucagon, immunoreactive insulin, beta-endorphin, rT3, 11-beta-hydroxyandrostenedione), but there are hormones that are unually low (T4, FSH, androstenedione, progesterone--the latter especially in females). Calcitonin, parathyroid hormone, growth hormone are sometimes elevated, as well as LH (measured with RIA methods). TSH is usually normal, the biologically measured LH was reported to be low. The levels of the sensitive indicators of burn stress may be used to evaluate the effect of treatment: if the burn patient is properly treated, the indicators may become earlier normal.
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PMID:Endocrine changes after burn trauma--a review. 251 73


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