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)

Hypothalamic regulatory peptides bind to specific receptors on target cells in the pituitary and control secretion. They in turn can be regulated at the pituitary level by steroid and peptide modulators. Affinity cytochemical techniques are important tools for the identification of specific target binding sites for these regulatory peptides. This presentation reviews the work in which potent, biotinylated ligands of gonadotropin releasing hormone (bio-GnRH), corticotropin releasing hormone (bio-CRH), and arginine vasopressin (bio-AVP) were applied to study the target cell responses. Bio-GnRH, bio-CRH, and bio-AVP bind to membrane receptors on specific anterior pituitary cells. Dual labeling for either gonadotropin or adrenocorticotropin (ACTH) antigens further identified the target cells. After 1-3 minutes, the label was in patches or capped on the surface. After 3 minutes, it was internalized in small vesicles and sent to receptosomes and vacuoles in the Golgi complex. Eventually the biotinylated peptides, or a metabolite, was found in the lysosomes (multivesicular bodies) and a subpopulation of secretory granules. The route and rate of uptake was similar to that described for the classical receptor-mediated endocytosis process. In contrast, intermediate lobe corticotropes internalized the bio-CRH in less than 1 minute. The route through the Golgi complex appeared to be bypassed. Instead the labeled peptide was in vesicles, on the membranes of scattered vacuoles, and in multivesicular bodies. Modulation of ligand binding by steroids showed that changes in receptor numbers correlated with changes in the number of cells that bound the ligand. In male rats, dihydrotestosterone reduced the percentage of GnRH-bound cells by 50%. Most of the reduction appeared in cells that stored luteinizing hormone (LH) antigens. In diestrous female rats, estradiol increased the percentage of bio-GnRH-bound cells. However, the steroid decreased the percentage of GnRH-bound cells in cells from proestrous rats. Glucocorticoids decreased the percentage of CRH-bound corticotropes in as little as 10 minutes. Potentiation of secretion by these ligands was correlated with increases in the percentage of ligand-bound cells. AVP pretreatment of corticotropes increased the percentage of cells that bound bio-CRH. It also increased the rate of receptor-mediated endocytosis of CRH and changed the route so that the Golgi complex was bypassed. This effect could be mimicked by activation of its second messengers (calcium and protein kinase C). Similarly, CRH pretreatment increased the percentage of corticotropes that bound AVP. Thyrotropin releasing hormone (TRH) pretreatment also increased the percentage of thyrotropes that bound AVP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Hypothalamic regulatory peptides and their receptors: cytochemical studies of their role in regulation at the adenohypophyseal level. 166 66

1. In rats, recovery of sensory-motor function following a crush lesion of the sciatic or tibial nerve was monitored by measuring foot reflex withdrawal from a local noxious stimulation of the foot sole. 2. Putative neurotrophic compounds were tested on this functional recovery model: melanocortins (peptides derived from ACTH (corticotropin) and alpha-MSH (melanotropin], gangliosides and nimodipine were effective whereas isaxonine and TRH (thyrotropin releasing hormone) were not. 3. Structure-activity studies with melanocortins revealed a similar effectiveness of alpha-MSH, [N-Leu4, D-Phe7]-alpha-MSH, desacetyl-alpha-MSH and the ACTH analogue ORG 2766, questioning the validity of the previously suggested notion that the melanotrophic properties of these peptides are responsible for their neurotrophic effect. 4. As recovery of function after peripheral nerve damage follows a similar time course in hypophysectomized (five days post operation) and sham-operated rats, effective melanocortin therapy does not mimic an endogenous peptide signal in the repair process from pituitary origin. 5. Subcutaneous treatment with ORG 2766 (7.5 micrograms kg-1 48 h-1) facilitates recovery of function following peripheral nerve damage in young (6-7 weeks old), mature (5 month old) and old (20 month old) rats. 6. In view of the diversity in structure of the effective neurotrophic factors and the complexity of nerve repair, the present data support the notion that peripheral nerve repair may be facilitated by different humoral factors likely to be active on different aspects of the recovery process.
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PMID:Putative neurotrophic factors and functional recovery from peripheral nerve damage in the rat. 167 80

There was no apparent difference in the regional distribution of neuropeptides in the brain of male and female rats. The highest levels of immunoreactive leu-enkephalin, TRH, substance P and somatostatin were found in the hypothalamus, while the striatum and the cerebral cortex had the highest concentrations of met-enkephalin and cholecystokinin respectively. The lowest concentrations of these were found in the cerebellum. Enkephalins (cerebral cortex), substance P (cerebral cortex and brain stem), and somatostatin (brain stem and striatum) showed higher level in the female while enkephalin and substance P contents in the anterior pituitary were higher in the male.
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PMID:The regional distribution of thyrotropin releasing hormone, leu-enkephalin, met-enkephalin, substance P, somatostatin and cholecystokinin in the rat brain and pituitary. 171 78

It was previously shown in this laboratory that high affinity binding of [125I]ACTH-(1-24) to membranes from rat brain was inhibited by vasoactive intestinal polypeptide (VIP), GH-releasing factor (GRF), and dynorphin (DYN), but not by other peptides tested. We now show that these peptides compete for [125I]VIP binding in brain and for [125I]ACTH-(1-24) binding in adrenal cortex and promote steroidogenesis. The high affinity sites for [125I]ACTH-(1-24) in the rat brain and bovine adrenal had Kd values of 0.51 +/- 0.41 and 3.9 +/- 1.3 nM, respectively; and the Ki values for VIP were 5.4 +/- 4.2 and 1.4 +/- 0.51 nM, respectively. In rat brain and bovine adrenal the high affinity site for [125I]VIP had Kd values of 2.9 +/- 1.7 and 0.5 +/- 0.8 nM, respectively, and Ki values for ACTH of 23.6 +/- 14.0 and 22.2 +/- 33.0 nM, respectively. In brain, DYN and GRF inhibited binding of [125I]VIP with Ki values of 49 and 30 nM, respectively. Cortisol secretion from isolated bovine adrenal cortical cells was significantly stimulated by 10(-10) M ACTH, VIP, DYN, or GRF, and a maximal response occurred for each at 10(-8) M. However, maximal cortisol production in response to VIP, DYN, or GRF was only about half that by ACTH-(1-24). The combination of ACTH-(1-24) and VIP, each at 10(-10) M, was additive in stimulating cortisol production, whereas each at 10(-8) M caused no greater response than ACTH alone. There was an additive steroidogenic effect of VIP plus ACTH-(1-10), but not VIP plus ACTH-(11-24). Specific binding of [125I]ACTH-(11-24) in adrenal membranes was inhibited by unlabeled ACTH-(11-24), ACTH-(1-24), VIP, GRF, and DYN, but not by ACTH-(1-10), peptide T, TRH, alpha MSH, or beta-endorphin; there was no specific binding of [125I]ACTH-(1-10). Functional studies and binding data, in conjunction with the existence of homologous amino acid sequences, indicate that VIP, GRF, and DYN interact at a subpopulation of ACTH receptors that recognizes a moiety within the 11-24 sequence of the ACTH molecule.
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PMID:Adrenocorticotropin, vasoactive intestinal polypeptide, growth hormone-releasing factor, and dynorphin compete for common receptors in brain and adrenal. 196 78

The finding of endocrine gland lesions at pathological examination in AIDS and reports of several cases of endocrine disease in patients with this syndrome have prompted us to study endocrine functions in 63 patients (51 men, 12 women) with HIV-1 infection. According to the Center for Disease Control (CDC) classification system, 13 of these patients were stage CDC II, 27 stage CDC III and 23 stage CDC IV. We explored the adrenocortical function (ACTH, immediate tetracosactrin test) and the thyroid function (free T3 and T4 levels, TRH on TSH test) in all 63 patients. The hypothalamic-pituitary-gonadal axis (testosterone levels, LHRH test) and prolactin secretion (THR test) were explored in the 51 men. The results obtained showed early peripheral testicular insufficiency at stage CDC II and early pituitary gland abnormalities with hypersecretion of ACTH and prolactin also at stage CDC II. On the other hand, adrenocortical and pituitary abnormalities were not frequently found. The physiopathology of the endocrine abnormalities observed in HIV-1-infected patients remains unclear, but one may suspect that it involves interleukin-1 since this protein factor has recently been shown to stimulate the corticotropin-releasing hormone secretion and to act directly on the glycoprotein capsule of the virus (gp 120) whose structure is similar to that of some neurohormones.
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PMID:[Endocrine abnormalities in HIV infections]. 216 75

Previous studies have demonstrated that TRH is a potent stimulator of alpha-MSH secretion from frog pituitary melanotrophs. In order to determine the intracellular events responsible for TRH-evoked alpha-MSH release, we have investigated the effect of TRH on polyphosphoinositide breakdown in frog pars intermedia. Neurointermediate lobes were labelled to isotopic equilibrium with myo-[3H]inositol. TRH stimulated the rate of incorporation of [3H]inositol into the phospholipid fraction. The effect of TRH was concentration-dependent; half-maximal stimulation of alpha-MSH release and inositol incorporation occurred at 12 and 28 nmol TRH/l respectively. In prelabelled neurointermediate lobes, lithium (10 mmol/l) enhanced the radioactivity in inositol monophosphate, bisphosphate (IP2) and trisphosphate (IP3). LiCl (10 mmol/l) induced a 38% inhibition of alpha-MSH release from perifused neurointermediate lobes but did not impair TRH-induced alpha-MSH secretion. In the presence of LiCl, TRH (1 mumol/l) induced a transient increase of the radioactivity in IP3, which was evident by 30 s and maximal by 1 min (+100%). TRH treatment also increased the radioactivity in IP2, which reached a plateau after 5 min (+100%). The increase in radioactivity in IP3 induced by TRH was closely paralleled by a rapid loss of [3H]phosphatidylinositol bisphosphate (PIP2), which was maximal by 1 min (-70%). These results indicate that, in frog pars intermedia, TRH-evoked alpha-MSH secretion is coupled to breakdown of PIP2. The data suggest that, in amphibian melanotrophs, as previously shown in GH3 tumour cells and in rat pituitary mammotrophs, TRH causes rapid stimulation of polyphosphoinositide-hydrolysing phospholipase C.
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PMID:Thyrotrophin-releasing hormone stimulates polyphosphoinositide metabolism in the frog neurointermediate lobe. 217 40

The existence of a short-loop feedback inhibition of pituitary ACTH release by administration of beta-endorphin was postulated. However, data on the effect of peripherally administered beta-endorphin in humans are highly controversial. We infused human synthetic beta-endorphin at a constant rate of 1 microgram.kg-1.min-1 or normal saline to 7 normal volunteers for 90 min. Thirty min after starting the beta-endorphin or placebo infusion, releasing hormones were injected as a bolus iv (oCRH and GHRH 1 microgram/kg, GnRH 100 micrograms, TRH 200 micrograms) and blood was drawn for measurements of beta-endorphin immunoreactivity, all other pituitary hormones, and cortisol. Infusion of beta-endorphin resulted in high beta-endorphin plasma levels with a rapid decrease after the infusion was stopped. During the control infusion, beta-endorphin plasma levels rose in response to CRH. Plasma ACTH and serum cortisol levels in response to the releasing hormone were not different in subjects infused with beta-endorphin or placebo. The PRL response to TRH was significantly higher after beta-endorphin than after placebo (area under the stimulation curve 1209 +/- 183 vs 834 +/- 104 micrograms.l-1.h). There was no difference in the response of all other hormones measured. Our data on ACTH and cortisol secretion do not support the concept of a short-loop negative feedback of beta-endorphin acting at the site of the pituitary.
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PMID:Infusion of beta-endorphin has no suppressive effect on the releasing hormone-stimulated pituitary-adrenal-axis of normal human subjects. 217 40

Histamine (HA), which acts as a neurotransmitter in the central nervous system, participates in the neuroendocrine regulation of prolactin (PRL) secretion. HA has a predominant stimulatory effect which is mediated via H2-receptors following central administration and via H1-receptors following systemic infusion of the amine. In addition, HA seems to exert a minor inhibitory effect on PRL secretion, an effect unmasked only during blockade of the receptor mediating the stimulatory effect. Following central administration the inhibitory effect is mediated via H1-receptors, while following systemic administration this effect is mediated via H2-receptors. In accordance with these findings, the H2-receptor antagonist cimetidine (CIM) has an inhibitory (following central administration) or stimulatory (following systemic administration) effect on PRL secretion. However, high doses of CIM possess an additional PRL stimulatory action not related to blockade of H2-receptors. This non-specific action is not exerted by the chemically different H2-receptor antagonist ranitidine. Since HA has no effect directly at the pituitary level, the actions of the amine may occur at different sites within the hypothalamus by an effect on hypothalamic transmitters regulating PRL secretion. Dopaminergic as well as serotoninergic neurons are involved in the mediation of the action of HA, since the dopamine (DA) concentration in the pituitary portal vessels is decreased by central or systemic infusion of HA, and since blockade of DA synthesis and of DA or serotonin (5-HT) receptors inhibit or prevent the PRL stimulatory action of HA infused centrally or systemically. However, other factors regulating PRL secretion (e.g. beta-endorphin, vasoactive intestinal peptide, vasopressin or TRH) may be involved in the mediation of the PRL response to HA. In men the effects of HA on PRL secretion are similar to the effects in male rats. Systemic infusion of HA stimulates PRL secretion via H1-receptors and inhibits PRL secretion via H2-receptors. The PRL-stimulatory effect of HA is caused by an inhibition of the dopaminergic system, while the PRL-inhibitory effect of HA may involve other transmitters than DA. In contrast to its stimulatory effect in men, HA had no effect on basal PRL secretion in women, but enhanced the PRL response to TRH. In rats or in humans the PRL stimulatory effect of HA is not caused by the cardiovascular actions of the amine.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Histaminergic regulation of prolactin secretion. 218 99

The beta-endorphin hypothesis of late luteal phase dysphoric disorder (premenstrual syndrome or L2D2) was tested. Twenty-two PMS patients were compared to twenty-two controls. Levels of beta-endorphin, ACTH, FSH, LH, cortisol, prolactin and TRH were measured on the first and twentieth days after menses. PMS subjects exhibited a significantly greater drop in the opiate, beta-endorphin, (p less than .001) than controls. No relationship or significant e was seen with the other hormones/transmitters tested. The symptoms of PMS may be due to noradrenergic rebound following beta-endorphin decline. Symptomatic and pharmacological morphine withdrawal and manic phase of bipolar disorder are discussed as possible models for L2D2.
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PMID:Beta-endorphin decline in late luteal phase dysphoric disorder. 226 89

Pituitary apoplexy is characterized by a wide spectrum of clinical features. A quite rare case of painless thyroiditis, hypopituitarism and central diabetes insipidus (DI) followed by pituitary apoplexy was presented. A 61-year-old woman was admitted to our hospital in May, 1986 because of marked general malaise, polydipsia and weight loss which became progressively worse. Four months earlier she had experienced episodes of abrupt onset of severe headache associated with nausea and blurring vision. Physical examinations revealed a fine tremor, dry skin and nervousness. The thyroid gland was not palpable. Visual fields were intact. Her blood pressure was 105/64 mmHg with variable tachycardia. The routine laboratory studies were normal or negative except for hypoalbuminemia, hypocholesterolemia and hypernatremia. Erythrocyte sedimentation rate was 12 mm/hr. An impairment in corticotropin secretion was suspected from the low plasma cortisol and the low urinary excretion of 17-OHCS and the sufficient response to ACTH. Basal levels of GH and gonadotropin were also low, and responses to the stimulation tests (Insulin-stress, L-DOPA, and LH-RH) were all blunted. Brain computed tomographic scan and magnetic resonance imaging demonstrated a suprasellar mass that, after infusion, developed peripheral ring-like enhancement and large hyperintense pituitary mass, respectively. A diagnosis of pituitary apoplexy with anterior pituitary failure was made. However, the initial levels of thyroid hormones showed elevated as follows: Free T3 7.6 pg/ml, Free T4 3.3 ng/dl and T3-resin uptake 41.1%. TSH responses to TRH were all suppressed. TSH receptor antibody (TBII) was negative. Both antithyroglobulin and antimicrosomal antibodies were repeatedly positive. A thyroid scan with 99mTc revealed no uptake in the thyroid area. These findings led us to the diagnosis of "painless autoimmune thyroiditis". She had become hypothyroid without any medication. At that time radioactive 99mTc and 123I uptakes increased significantly. When hydrocortisone was substituted, daily urine output abruptly increased to about 10 liters with low osmolality, and the presence of DI was suspected. This diagnosis was confirmed by water deprivation and hypertonic saline infusion tests and subsequent pitressin test. She is currently quite well on L-thyroxine, hydrocortisone and desmopressin (1988). This association with pituitary apoplexy must be a rare occurrence, as a literature search has failed to find a similar case. The pathogenetic trigger of "painless thyroiditis" in this case may be responsible for some immunological change due to secondary adrenal insufficiency after pituitary apoplexy.
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PMID:[An unusual association of transient resolving thyrotoxicosis due to painless thyroiditis, hypopituitarism and central diabetes insipidus associated with spontaneous pituitary apoplexy]. 230 57


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