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)

TRH has been shown to be present in the pancreas. To examine a possible role for TRH in the control of endocrine pancreatic function, we have studied the effects of TRH on the isolated perfused rat pancreas preparation. Arginine caused release of TRH from the preparation. The mean maximum TRH peak was 85 +/- 12 pg/ml and occurred later than the first phase of glucagon release. Glucagon (2000 pg/ml) did not release TRH from the preparation. There was no detectable basal release of TRH. Glucose did not stimulate release of TRH from the pancreas preparation. TRH (10 ng/ml) by itself had no effect on insulin or glucagon release. TRH enhanced arginine-induced glucagon release; mean summated glucagon was 8228 +/- 1138 (SE) pg/ml compared to controls (4530 +/- 447 pg/ml; P less than 0.01). There was a tendency for TRH to enhance second phase glucose-induced insulin release. Pancreatic physiology is in part regulated by locally acting hormones and TRH may be one of these hormones.
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PMID:The effects of thyrotropin-releasing hormone on the endocrine pancreas. 10 72

Combined Glucagon-Propranolol test used for study of growth hormone is advantages. The combined administration of TRH and LHRH is possible. In 53 children, the hormone responses (GH, TSH, FSH, LH and prolactin) were studied. This combined test allows the rapid assessment of anterior pituitary function.
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PMID:[Combined test for assessment of anterior pituitary function using glucagon-propranolol, TRH and LHRH (author's transl)]. 11 72

Several procedures have been reported for the assay of corticotrophine-releasing factor (CRF), each having its advantages and disadvantages. This report deals with an in vitro assay of ACTH releasing activity utilizing pituitary incubation combined with ACTH radioimmunoassay. Rat half pituitary was preincubated in 2 ml Krebs Ringer bicarbonate buffer containing 0.2% glucose and 0.25 % BSA (KRBG-BSA) for 1.5 hr (45 min X 2). The medium was replaced by 1 ml KRBG-BSA and incubated for 30 min. Then the medium was again replaced by 1 ml KRBG-BSA or KRBG-BSA containing test materials and incubated for another 30 min. The amount of ACTH assayed by radioimmunoassay in the 2nd 30 min incubation was compared with in the 1st 30 min incubation and expressed as percentage. In ACTH radioimmunoassay, anti-ACTH serum was diluted to 1 : 1,500-3,000. The 125I-alpha 1-24ACTH-antibody system was not affected by lysine-vasopressin (LVP), arginine-vasopressin (AVP), rat's pituitary LH, GH and prolactin. Human 1-39ACTH was used as ACTH standard, and the dilution curve of incubation medium was paralleled with the standard curve. Repeatability of immunoassayable ACTH within-assay was 174 +/- 5.0 pg/tube (CV = 2.9%). A log dose-relationship was observed between the amounts of stalk median eminence extracts (SME ; NIAMDD) added to the incubation medium and its ACTH releasing activities. The sensitivity of this assay method was at least 0.1 SME or 10 mU of LVP and AVP. Using this method, it found that LVP, AVP, norepinephrine (100 ng/ml200 ng/ml) and 5-hydroxytryptophane (1 mug/ml) had ACTH releasing activities but LH-RH, TRH, glucagon, dopamine, phentolamine, propranolol, haloperidol, prostaglandin E1 and indomethacin did not affect the release of ACTH.
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PMID:[In vitro assay for ACTH-releasing activity using ACTH radioimmunoassay: ACTH releasing activities by various drugs (author's transl)]. 18 1

The adenylate cyclase responses of the human GH or ACTH producing pituitary adenomas and ectopic ACTH producing tumors to TRH, LH-RH, biogenic amines, peptides hormones, PGE1 and rat median eminence extract (MEE) have been examined. Out of 4 GH producing pituitary adenomas obtained from patients with active acromegaly at hypophysectomy two were stimulated by TRH, two by LH-RH, three by norepinephrine, one by dopamine, four by PGE1 and none by serotonin. Glucagon stimulated the adenylate cyclase in one of three and MEE in both of two tested. The positive responses of paradoxical GH release after TRH and/or LH-RH before surgery in these patients coincidentally related to the response of adenylate cyclase of each pituitary adenoma. There seems, however, to be no consistent correlation between the adenylate cyclase responses to biogenic amines and the GH release after L-Dopa or 5-hydroxytroptophan tested. The adenylate cyclase of a pituitary adenoma from case of Cushing's disease was stimulated by LH-RH, norepinephrine glucagon and MEE but not by TRH. Plasma levels of ACTH, beta-MSH and cortisol increased after LH-RH but not after TRH in this patient before hypophysectomy. The adenylate cyclase of two ectopic ACTH producing tumors (gastric carcinoid and malignant thymoma) was activated by TRH, LH-RH, norepinephrine, epinephrine, serotonin, PGE1 and MEE. These results indicate the presence of multiple hormone receptors in GH or ACTH producing pituitary adenomas and ectopic ACTH producing tumors, and suggest that the paradoxical GH or ACTH release after TRH and/or LH-RH injection in acromegaly and Cushing's syndrome might be caused by an alteration of the cellular membrane receptors of the pituitary adenomas.
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PMID:Adenylate cyclase of GH and ACTH producing tumors of human: activation by non-specific hormones and other bioactive substances. 19 Feb 56

A case of pseudohypoparathyroidism has been investigated. Indirect evidence allows to eliminate a defect of renal 1 alpha-hydroxylase as the determining factor of this condition. Similarly, the increased size of the mean surface area of the cross-section of periosteocytic lacunae, as determined on decalcified sections of bone obtained by transiliac biopsy, shows the osteocytes to be sensitive to the endogenous PTH, discarding cAMP response to PTH in bone as a prerequisite for PTH action on bone. The authors conclude from these data and from previous experiments that the defect of parathyroid function in this condition probably relates to the existence of an abnormal PTH molecule and/or metabolism and/or interaction with the receptors sites. The endocrine function was studied as well. Prediabetes was demonstrated, as well as primary latent hypothyroidism (TRH test). Prolactin release could not be stimulated by TRH, levodopa, metoclopramide, chlorpromazine and insulin hypoglycemia. The latter produced a normal release of ACTH (as ascertained by plasma cortisol levels) and GH, and possibly a sluggish response of glucagon and gastrin. There was a deficiency of urinary concentration upon restriction of fluid intake. This was only partially corrected by ADH administration.
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PMID:[Physio-pathology of pseudohypoparathyroidism (author's transl)]. 22 97

In 7 acromegalic patients growth hormone responses were studied following administration of synthetic TRF, propranolol-glucagon, insulin, and glucose p.o. Except for the glucose tolerance test, a good reproducibility of the STH response was observed. In 5 out of the 7 patients, there was a distinct rise in the plasma STH level after TRF. All patients with a positive insulin tolerance test responded to TRF, as did the two late responders to glucagon; the early responder to the latter test did not respond to TRF. It has been suggested (Liuzzi et al. 1974a) that TRF might be used as a screening test for detecting hypothalamic dependency of the acromegaly. This study suggests that further study is required before accepting this hypothesis and that a response to a combination of tests (TRF, glucagon, insulin) might be a better screening method.
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PMID:Comparison of TRF, propranolol-glucagon, insulin and glucose stimulation tests in acromegaly. 40 15

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 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

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

TRH is synthesized in the islets of Langerhans and was found in the perfusate of isolated rat pancreas. In the present study, designed to determine the role of endogenous TRH, we first characterized chromatographically the identity of immunoreactive TRH with synthetic pGlu-His-Pro-NH2. Since endogenous TRH secretion may mask the effects of exogenous TRH, we performed, in parallel to dose-response studies, immunoneutralization experiments using anti-TRH serum to neutralize the endogenous TRH secretion from isolated perfused rat pancreas. The data indicate that exogenous TRH enhances basal glucagon secretion; inversely, anti-TRH serum inhibits glucose plus arginine-induced glucagon secretion and produces a concomitant slight inhibition of somatostatin secretion. The present study shows a physiological contribution for endogenous TRH as a local modulator of intraislet hormone regulation; from these observations, we postulate a direct effect of pancreatic TRH on glucagon-containing (alpha) cell secretion, which, in turn, may produce the fluctuation in somatostatin secretion. Local TRH secretion provides a model for positive feedback regulation of glucagon secretion, frequently associated with diabetes.
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PMID:Antithyrotropin-releasing hormone serum inhibits secretion of glucagon from isolated perfused rat pancreas: an experimental model for positive feedback regulation of glucagon secretion. 163 22


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