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

Synthetic analogs of growth hormone-releasing hormone, GHRH(1-29)-NH2 and D-Ala2 GHRH(1-29)-NH2 were administered as a bolus intravenous injection to five normal men in a dose range of 0.015 to 0.5 micrograms/kg body weight. Vehicle only was administered in a control study. Peak responses to GHRH analogs occurred at 15 or 30 min. An increase in the integrated plasma growth hormone (GH) response was observed at each dose. The dose-response curve of GHRH(1-29)-NH2 indicated that it has a similar molar potency to GHRH(1-40) and GHRH(1-44). The potency of D-Ala2 GHRH(1-29)-NH2 was approximately twice that of GHRH(1-29)-NH2. Neither analog affected blood levels of PRL, TSH, LH, FSH, ACTH, insulin, glucagon, glucose, cortisol, free thyroxine, and free triiodothyronine. No side effects were noted other than transient flushing with the highest dose administered. The findings demonstrate GHRH(1-29)-NH2 and its D-Ala2 analog are potent stimulators of GH release and have potential application in clinical medicine.
 ...
PMID:Growth hormone responses to growth hormone-releasing hormone (1-29)-NH2 and a D-Ala2 analog in normal men. 286 96

Twelve patients with active acromegaly were treated with the long-acting somatostatin analogue SMS 201-995 (SMS), at a dose of 50 micrograms sc twice daily in the first 2 weeks of treatment and 100 micrograms sc thereafter. Four h after the first injection of SMS, GH levels became normal in 8 of the 12 patients. Basal glucose levels were significantly lower at the 28th day of treatment. This glucose lowering effect was stronger in the diabetic than in the nondiabetic patients. The postprandial rise of insulin levels was reversed by SMS, leading to a more pronounced postprandial rise of glucose, whereas the postprandial secretion of glucagon was also reversed by SMS. The rise of glucose levels during oral glucose loading was similar before and during SMS, despite a strong inhibitory effect of the drug on the insulin rise after glucose loading. Basal TSH levels were not influenced by SMS, the TRH-induced TSH response, however, was significantly blunted. Although the basal PRL levels were significantly reduced by SMS, the TRH-induced PRL rise was similar before and during administration of the analogue. Paradoxical GH responses to TRH disappeared in 7 out of 8 patients during SMS. Paradoxical GH responses to GnRH, however, persisted in 4 out of 4 patients. Paradoxical responses of GH after glucose loading disappeared in 2 out of 2 patients. The GH response after GHRH administration was strongly suppressed by SMS. During long-term treatment (up to 2 years), the GH level obtained within 5 h after the last injection of SMS remained normal in the patients whose GH levels normalized at the first day of treatment. There was a good response of the disease to this treatment, and no serious adverse reactions were observed. We conclude that SMS normalizes most anomalous growth hormone kinetics in acromegaly. The drug offers a new tool in the treatment of this disease.
 ...
PMID:Long-term treatment of acromegaly with Sandostatin (SMS 201-995). Normalization of most anomalous growth hormone responses. 289 39

The purpose of the present investigation was to characterize and determine what hormones affect the activity of aromatase in human fetal hepatocytes maintained in primary monolayer culture. The major product of aromatization of androstenedione was estrone sulfate. Optimal conditions for assay of aromatase activity in fetal liver cells were determined. The apparent Km for androstenedione was 50 nM. Aromatase activity was stimulated by glucocorticoids in the presence of fetal calf serum. The concentration of dexamethasone required for half-maximal stimulation was 10(-8) M, similar to the concentration required for half-maximal binding to glucocorticoid receptors. This action of dexamethasone was inhibited by cortisol 21-mesylate, a glucocorticoid antagonist. Aromatase activity was also stimulated by (Bu)2cAMP and cholera toxin, and was inhibited by fetal calf serum. This effect of fetal calf serum was mimicked by epidermal growth factor. However, epidermal growth factor did not mimic the permissive action of serum to stimulate aromatase activity by dexamethasone. In these respects, the regulation of aromatase activity of human fetal hepatocytes is similar to that of human adipose stromal cells. A polycyclic hydrocarbon, benzo(a)pyrene, which causes induction of aryl hydrocarbon hydroxylase activity in fetal hepatocytes, inhibited the stimulation of aromatase activity by dexamethasone. Of a number of hormones tested, including glucagon, insulin, angiotensin II, ACTH, hCG, GH, PRL, and T3, only glucocorticoids were effective in stimulating aromatase activity of human fetal hepatocytes. These results emphasize the complex and multiparameter nature of the regulation of aromatase activity in this as in other tissues.
 ...
PMID:Factors affecting the conversion of androstenedione to estrogens by human fetal hepatocytes in monolayer culture. 298 22

This report describes a new method for detecting and quantitating those immunoglobulins G (IgG) in serum that are related to Graves' disease. The method is based on previous observations which indicate that the guinea pig fat cell membrane (FCM) is capable of binding Graves'-specific IgG, but does not bind the IgG common to Graves' disease and Hashimoto's disease, such as antimicrosomal antibodies. Crude FCM preparations were iodinated by a lactoperoxidase technique and were then treated with Triton X-100 to yield a solubilized radioiodinated FCM (SFCM) preparation. SFCM, which retained bovine (b) TSH binding and Graves'-IgG binding properties, provided a radioactively labeled receptor with which to test for the presence of fat cell-binding IgG (FBI) in immunoprecipitates prepared by reacting these IgG with antibody against the Fc fragment of human IgG. FBI values (percentage of added SFCM bound to immunoprecipitate; mean + SD) in IgG from 16 patients with thyrotoxicosis caused by Graves' disease (6.0 +/- 1.7) were completely separated from those in IgG from 16 normal subjects (0.4 +/- 0.3). IgG from 2 hypothyroid patients with Hashimoto's disease, which were strongly positive in the TSH binding inhibition (TBI) assay, yielded FBI values within the range in Graves' disease, but values in TBI-negative IgG from 15 other patients with Hashimoto's disease were normal (0.0 +/- 0.9). Moderately false positive FBI values were found in the IgG of 15 patients with rheumatoid arthritis or systemic lupus erythematosis, all rheumatoid factor positive, 3 of which were also TBI positive. In IgG from Graves' disease and those from patients with TBI-positive collagen-vascular disease, binding of SFCM was inhibited by bTSH in a dose-dependent manner. As with binding of TSH to thyroid plasma membranes, similar but less potent inhibition of binding of IgG to SFCM was produced by LH, FSH, and hCG, but not by insulin, glucagon, PRL, or ACTH. FBI values in TBI-negative IgG from patients with collagen-vascular disease were also decreased by TSH, but higher concentrations of bTSH were required. In 40 IgG from among the various clinical groups tested, a significant correlation was found between FBI values and TBI activity (r = 0.48; P less than 0.01). In addition, among 10 IgG from Graves' disease and 6 from collagen-vascular disease patients, a very close correlation (r = 0.89; P less than 0.001) was noted between their TBI activity and the extent to which their FBI values were decreased by a standard concentration of bTSH.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Detection and measurement of fat cell-binding immunoglobulins: a new method applicable to the diagnosis and study of Graves' disease. 299 73

The effect of conditioned vs. fresh culture medium on the dopaminergic inhibition of TSH and PRL secretion by primary cultures of male rat anterior pituitary cells has been studied. In the presence of conditioned medium (that had been in contact with the cells over the 3-day culture period) 10(-6) M dopamine (DA) inhibited PRL secretion by 50% and TSH secretion by 30%. After 4 h of incubation with fresh medium 10(-6) M DA still inhibited PRL secretion by 50% but increased TSH release by 20%. TSH release was rapid and could be prevented by 10(-6) M prazosin, an alpha 1 adrenoreceptor antagonist. Fresh medium did not alter TRH induced TSH release. In parallel cultures and under identical conditions fresh medium reduced [3H]dihydroergocryptine (DHE) binding to DA receptors from 2.5 +/- 0.4 fmol/10(5) cells to 0.95 +/- 0.3 fmol/10(5) cells (means +/- SEM, n = 5, P less than 0.001). The effect of fresh medium was dose dependent against the dopaminergic inhibition of TSH secretion and against DA receptor binding. If 1 mU TSH was included, in fresh medium, the dopaminergic inhibition of TSH secretion remained unchanged and [3H]DHE binding to DA receptors did not fall. The rank order of potency of thyroid stimulators was bovine TSH (21 U/mg) greater than semipurified bovine TSH (Thytropar, 1.4 U/mg) greater than endogenous rat TSH (0.03 U/mg expressed as NIADDK-rat TSH-RP2) greater than Graves' immunoglobulin G (0.01 U/mg) when either DA or bromocriptine was used as the dopaminergic agonist. When anterior pituitary cells from hypothyroid rats were examined, the effects of culture medium on the dopaminergic inhibition of TSH and on DA receptor binding were approximately twice those observed in normal cells, but the inclusion of 1 mU TSH in the fresh medium completely prevented the loss of DA function and binding. PRL, human CG, ACTH, insulin, glucagon, and heat-inactivated TSH were unable to prevent the effect of medium replacement on dopaminergic inhibition of TSH and DA receptor binding. The data suggest a mechanism whereby TSH may control its own secretion via DA.
 ...
PMID:Thyrotropin regulates thyrotroph responsiveness to dopamine in vitro. 300 10

Binding of either "cold" or 125I-PRL to their specific receptors (fraction after centrifugation at 15,000 and 100,000 X g) obtained from late pregnant rat liver, pre- and post-dissociation with MgCl2, has been studied. Binding was higher with cold hormone (delta 21.63%) than with 125I-PRL. Similarly, binding to the 100,000 X g fraction was also higher than to the 15,000 X g one. Dissociation by MgCl2 improved binding to the 100,000 X g fraction (delta 17.27%), while reduced the 15,000 X g fraction binding (delta 11.71%), underlying the impurity of the latter fraction. Control studies with rLH, rFSH, hACTH, insulin, glucagon and hGH evidenced the specificity of the preparation to bind lactogenic hormones. Binding increases with PRL and receptor concentration, reaching equilibrium between bound PRL/unbound PRL. An amount of PRL unable to bind to the receptor is always present. Even with high receptor concentrations (3,500 micrograms/0.1 ml) there is still about 25% of unbound PRL. When reincubating this previously unbound PRL with a fresh receptor preparation identical to the one used in the first incubation, a similar proportion of bound PRL/unbound PRL is obtained. These results suggest the existence of a heterogeneity in the receptor preparation.
 ...
PMID:[Evaluation of free and bound fractions resulting from the interaction of prolactin with its specific receptors]. 301 75

This study demonstrates that the threshold of glucose-stimulated insulin secretion can be regulated in vivo by long term hormonal and nutrient modifications. The sensitivity of the pancreatic B-cell to glucose stimulation was determined by examining the pattern of insulin release from pancreases perfused with linear glucose gradients. Male rats infused with ovine PRL for 4 days and rats receiving five hourly injections of glucose had a lower threshold and enhanced rates of insulin release at all stimulatory glucose concentrations. Infusion of bGH for 4 days was without effect on glucose gradient-stimulated insulin release. Fasting the rats for 48 h resulted in an elevation of the threshold and a substantial reduction in the extent of insulin release. To determine possible processes involved in these long term modifications of the threshold of glucose-stimulated insulin secretion, the in vitro effect of potentiators of insulin release was examined. Forskolin, glucagon, cholecystokinin, and carbamylcholine were able to lower the threshold and increase the extent of insulin release. This suggests that the long term regulation of insulin secretion may modulate processes controlling cAMP concentrations and the hydrolysis of phosphoinositides in pancreatic B-cells. Also, the proposed incretin gastric inhibitory polypeptide was capable of lowering the threshold and increasing insulin secretion at stimulatory glucose concentrations. The consequences of a decreased threshold is a markedly enhanced insulin secretion at normal serum glucose concentrations.
 ...
PMID:Nutrient and hormonal regulation of the threshold of glucose-stimulated insulin secretion in isolated rat pancreases. 304 73

Although early work implicated PRL as the pituitary factor inducing rat hepatic PRL receptors, recent studies indicated that GH, not PRL, was responsible. The roles for these two hormones were evaluated on rat hepatocytes cultured in serum-free medium supplemented with insulin (1 microgram/ml), epidermal growth factor EGF (25 ng/ml), glucagon (500 ng/ml), cholera toxin (2 ng/ml), hydrocortisone (10(-8) M), and transferrin (1 microgram/ml) and changed daily. Ovine (o) PRL, bovine (b) GH, or human (h) GH were introduced after 2-4 days of culture, and PRL receptors were measured by determining [125I]hGH binding in the presence and absence of excess oPRL in a total particulate fraction pretreated with 3 M MgCl2. The specific binding of hGH (% per 100 micrograms protein) decreased by 8- to 10-fold (female, 17.9 +/- 0.2% to 1.5%; male, 7.0 +/- 0.1% to 0.7%) after 3 days in culture. When added after 3 days, hGH induced PRL receptors in both female and male cells with the effect being more gradual in the latter. Induction occurred with 10 ng/ml hGH and was maximal [11- to 13-fold control] at 250-1000 ng/ml. bGH and oPRL also induced PRL receptors with maximal levels attained at 250-500 ng/ml oPRL (3- to 4-fold control). The combined addition of oPRL (300 ng/ml) and bGH (300 ng/ml) yielded levels of induction comparable to that seen with hGH. Although hormone treatment restored PRL receptor levels to those seen in male rats, the much higher levels of female rats were not attained. Treatment of hepatocytes with hGH, bGH, or oPRL affected neither cell number (through 10 days of culture) nor PRL receptor affinity. At supramaximal doses hGH, PRL, and bGH down-regulated PRL receptors, but this was particularly noticeable for oPRL and hGH. 17 beta-Estradiol and testosterone added to male and female hepatocytes simultaneously with hGH had little or no effect on receptor induction. We conclude that hepatic PRL receptors are induced by both PRL and GH, each acting through its own receptor. The failure to restore receptor levels to those seen in female rats attests to the importance of other modulators. This dual regulation of the PRL receptor explains the unusual potency of hGH which binds to both PRL and GH receptors.
 ...
PMID:Prolactin (PRL) receptor induction in cultured rat hepatocytes: dual regulation by PRL and growth hormone. 334 48

One group of 10 obese people (1.72 times normal weight) was compared to a control group of 9 normal-weight subjects. Oxygen consumption (VO2), immuno reactive growth hormone (IRGH), and rectal temperature (Tre) were measured every 15 min on an average, during the 5 h following a protein meal composed of 6 egg-whites and 50 g of casein totaling 1 340 kJ. The results show that postprandial thermogenesis (PPT) is the same in both groups: maximum increase in VO2 averages 15% in the obese and 16% in the control groups respectively. Energy expenditure integrated over the 5 h was 129 kJ for the obese and 114 kJ for the control subjects, i.e. 9.6% and 8.5% of the energy meal content. The rise in Tre was identical for both groups (0.4 degrees C over 3 h). For IRGH, the preprandial reference figures were much lower in the obese: 52 pmole.dm-3, as compared to 145 pmole.dm-3. In all control subjects, the protein meal resulted in a IRGH peak of, on average, 455 pmole.dm-3 about 2 h after. This was not observed in 4 of the obese subjects, while in the remaining 6, the mean peak value was 165 pmole.dm-3, occurring after 1 h. The other hormonal or chemical compound simultaneously analysed (glucagon, cortisol, PRL, T3, glucose, lactate, NEFA) do not show any significant variations but insulin blood level for which a postprandial increase was measured in both groups. It is concluded that after a protein test meal: PPT in overweight people is no different from that in people of normal weight.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Postprandial thermogenesis and hormonal release in lean and obese subjects. 391 63

The widespread occurrence of opioid peptides and their receptors in brain and periphery correlates with a variety of actions elicited by opioid agonists and antagonists on hormone secretion. Opioid actions on pituitary and pancreatic peptides are summarized in Table 1. In rats opioids stimulate ACTH and corticosterone secretion while an inhibition of ACTH and cortisol levels was observed in man. In both species, naloxone, an opiate antagonist, stimulates the release of ACTH suggesting a tonic suppression by endogenous opioids. In rats, a different stimulatory pathway must be assumed through which opiates can stimulate secretion of ACTH. Both types of action are probably mediated within the hypothalamus. LH is decreased by opioid agonists in many adult species while opiate antagonists elicit stimulatory effects, both apparently by modulating LHRH release. A tonic, and in females, a cyclic opioid control appears to participate in the regulation of gonadotropin secretion. Exogenous opiates potently stimulate PRL and GH secretion in many species. Opiate antagonists did not affect PRL or GH levels indicating absence of opioid control under basal conditions, while a decrease of both hormones by antagonists was seen after stimulation in particular situations. In rats, opiate antagonists decreased basal and stress-induced secretion of PRL. Data regarding TSH are quite contradictory. Both inhibitory and stimulatory effects have been described. Oxytocin and vasopressin release were inhibited by opioids at the posterior pituitary level. There is good evidence for an opioid inhibition of suckling-induced oxytocin release. Opioids also seem to play a role in the regulation of vasopressin under some conditions of water balance. The pancreatic hormones insulin and glucagon are elevated by opioids apparently by an action at the islet cells. Somatostatin, on the contrary, was inhibited. An effect of naloxone on pancreatic hormone release was observed after meals which contain opiate active substance. Whether opioids play a physiologic role in glucose homeostasis remains to be elucidated.
 ...
PMID:Endocrine actions of opioids. 608 80


<< Previous 1 2 3 4 5 Next >>