Melanocyte-stimulating Activity Research Articles

Vitiligo – Study In view of familial occurence

Vitiligo – Study In view of familial occurence

Efficacy Of Bastikarma In Vitiligo

Efficacy Of Bastikarma In Vitiligo

Adrenal Insufficiency in Critically Ill Patients

Patients with adrenal insufficiency in the critical care setting may present with a spectrum of disease severity ranging from life-threatening adrenal crisis to mild organ dysfunction. The recognition of adrenal insufficiency is made more difficult in the critically ill patient because of the unavailability of a reliable history, delay in reporting of diagnostic laboratory results, and the comorbidities that obscure a definitive diagnosis. The present discussion will illustrate how the classic presentations of adrenal insufficiency are modified in critically ill patients and how appropriate diagnosis and management can be achieved in the critical care setting. CLASSICAL PRESENTATIONS OF ADRENAL INSUFFICIENCY Adrenal insufficiency can be subdivided into three broad categories: ( 1 ) Chronic primary adrenal insufficiency, also called Addison’s disease, is a result of destruction of the adrenal cortex. The most common causes include autoimmune disease (about 70 to 80%), tuberculosis (about 20%), adrenal hemorrhage, adrenal metastases, and AIDS in association with cytomegalovirus (CMV), other pathogens, or ketoconazole treatment (1). ( 2 ) Chronic secondary adrenal insufficiency occurs when insufficient adrenocorticotropic hormone (ACTH) is available to stimulate the adrenal cortex. Most commonly it is due to exogenous glucocorticoid therapy, but it can also be the result of generalized hypopituitarism (usually from pituitary or hypothalamic tumors) or isolated ACTH deficiency (probably autoimmune in nature). ( 3 ) Acute adrenal crisis may result from stress in patients with chronic adrenal insufficiency who are not adequately replaced, but it also occurs in patients with acute adrenal hemorrhage or pituitary apoplexy. Both chronic primary and chronic secondary adrenal insufficiency lead to glucocorticoid deficiency and occasionally androgen deficiency (in women). The clinical features common to both primary and secondary adrenal insufficiency include hypotension, weakness, fatigue, anorexia, weight loss, nausea, and vomiting. Eosinophilia and normocytic anemia are common and occasionally one may see hypercalcemia. Hypoglycemia may be present particularly in children with primary adrenal insufficiency and in patients with secondary adrenal insufficiency in the context of panhypopituitarism when growth hormone is also missing. Chronic primary adrenal insufficiency may be accompanied by other autoimmune disorders (polyglandular failure), the most common being autoimmune thyroid disease (Grave’s or Hashimoto’s). Rarely, autoimmune hypoparathyroidism is present and such patients would be hypocalcemic. Two features distinguish primary and secondary adrenal insufficiency. First, mineralocorticoid deficiency is present in primary but absent in secondary (ACTH does not play a major role in regulation of aldosterone). For this reason, hyperkalemia is usually present in primary insufficiency but absent in secondary. Hyponatremia is a feature of both, but in primary insufficiency it is associated with volume contraction resulting in an elevated blood urea nitrogen (BUN) and creatinine. Hyponatremia in secondary adrenal insufficiency is dilutional because of decreased ability to excrete a water load and increased vasopressin levels. A second distinguishing feature is the high concentrations of ACTH and other propiomelanocortin (POMC)-derived peptides in primary insufficiency and the low or normal concentrations of these peptides in secondary insufficiency. This would typically lead to hyperpigmentation in primary insufficiency (from melanocyte-stimulating activity of POMC-derived peptides) and lack of hyperpigmentation, and occasionally pallor, in secondary insufficiency. Acute adrenal crisis is characterized by hypotension and shock, fever, confusion, nausea, and vomiting. In the setting of acute adrenal hemorrhage, many patients will also have abdominal, flank, or back pain. Pituitary apoplexy is usually associated with severe headache and frequently ophthalmoplegia. Laboratory abnormalities include azotemia and eosinophilia.

Calmodulin-binding peptides interfere with melanocyte-stimulating hormone receptor activity and stimulate adenosine 3',5'-monophosphate production in M2R mouse melanoma cells

Calmodulin-binding peptides interfere with melanocyte-stimulating hormone receptor activity and stimulate adenosine 3',5'-monophosphate production in M2R mouse melanoma cells

The melanocyte stimulating activity of N-nitroso-2-chloroethyl-carbamoyl derivatives of α-melanotropin fragments

A number of N-nitroso-2-chloroethyl-carbamoyl (Q(NO)) derivatives of α-melanotropin fragments have been synthesized and their effect on the frog skin melanocytes studied. Peptides substituted in this way possess the biological activity of the parent compounds, indicating that they preserved their receptor recognizing ability. These compounds can therefore serve as affinity labels. Some of these derivatives, related to the C-terminal sequence of α-melanotropin show prolonged darkening reaction, which does not influence the subsequent reaction of melanocytes with α-melanotropin. The Q(NO)-derivative of a fragment derived from the classical active site of the hormone shows, however, inhibition of the effect of α-melanotropin. It can be concluded that the latter peptide acts through the melanotropin receptor, while others, related to the C-terminal sequence of the hormone through another mechanism.

Catecholamine and serotonin concentrations in lymph nodes after deafferentation

Possible hormonal activity of ACTH4-7, a long-acting ACTH4-10 analog (ProGly Pro) was studied. Unlike ACTH5-10 the peptide did not reveal steroidogenic and melanocyte-stimulating activity.

Competence and progression growth factors stimulate different tRNA lys modification reactions in Balb/C 3T3 cells

Sparse cultures of Balb/C 3T3 cells were growth arrested in a medium containing 1% calf plasma. This treatment caused a decrease in tRNA4lys, a tRNA species related to cell division, and a corresponding increase in tRNA5lys. A restoration of tRNA4lys levels and an increase in cell number was obtained by the addition of either 10% calf serum or a combination of fibroblast growth factor and melanocyte stimulating activity. Neither growth factor alone evoked a proliferative response. The progression factors, insulin and multiplication stimulating activity stimulated the rapid conversion of tRNA5lys to tRNA2lys, whereas the competence factors, fibroblast growth factor and platelet-derived growth factor stimulated a slight conversion of tRNA2lys to tRNA4lys.

Solution synthesis of a heptacosapeptide known as bovine gamma 3-melanotropin (gamma 3-MSH).

A heptacosapeptide (known as γ3-MSH) which is located within the amino acid sequence of bovine corticotropin-β-lipotropin precursor protein was synthesized by fragment condensation of Z-(1-12)-OSu and H-(13-27)-OBzl followed by deprotection with trifluoromethanesulfonic acid-thioanisole in TFA. The synthetic peptide exhibited weak melanocyte-stimulating activity (1.5×106 U/g, in vitro).

Synthesis of the pentadecapeptide corresponding to the entire amino acid sequence of salmon alpha-melanotropin II (alpha-MSH II).

The pentadecapeptide corresponding to the entire amino acid sequence of α-MSH II, isolated from salmon pituitary gland, was synthesized by a conventional procedure. The synthetic peptide exhibited in vitro melanocyte-stimulating activity of 1.66×1010 MSH U/g.

ChemInform Abstract: SYNTHESIS AND MELANOTROPIC ACTIVITY OF Γ‐MELANOTROPIN

AbstractDas Titelpeptid (IIIb), eine weitere (dritte) melanotrope Sequenz im N‐terminalen Teil der ACTH‐ bzw. β‐LPH‐ Vorstufe Pro‐opiocortin, wird durch Kondensation der nach konventionellen Methoden aufgebauten Fragmente (I) und (II) [Azidmethode; ‐ (IIIa)] und nachfolgende Schutzgruppenabspaltung synthetisiert.

Synthesis of the Dodecapeptide Designated as Bovine γ-Melanotropin (γ-MSH)

The dodecapeptide corresponding to γ-melanotropin, a newly found amino acid sequence in bovine corticotropin-β-lipotropin precursor protein, was synthesized in a conventional manner. The synthetic peptide exhibited weak melanocyte-stimulating activity, but failed to show any significant steroidogenic and lipolytic activities.

The nature of the immunoreactive lipotropins in human plasma and tissue extracts.

This study was designed to establish definitively the nature of immunoreactive lipotropin (IR-LPH) in human plasma and tissue extracts. Using gel filtration, gel filtration under denaturing conditions, cationic exchange chromatography, immunoprecipitation, and radioimmunoassay, we have studied normal and tumorous human pituitaries, ectopic ACTH- and LPH-secreting tumors, plasma from normal subjects before and after dexamethasone administration, and plasma from patients with primary adrenal insufficiency and pituitary and nonpituitary ACTH- and LPH-secreting tumors. Except in the plasma and tumors of occasional patients with ectopic ACTH syndrome, the smallest IR-LPH appears to be lambda-lipotropin (lambdaLPH), which is often the predominant and occasionally the only IR-LPH present. The other major peptide appears to be betaLPH, a 91-amino acid molecule that contains lambdaLPH as its 1-58 sequence. Larger immunoreactive materials were observed in some specimens, but the "big" LPH in one plasma was shown to be lambdaLPH bound to IgG.The weak melanocyte-stimulating activity of LPH suggests that ACTH may be the principal pigmentary hormone in man. The fact that lambdaLPH, rather than betaLPH, is the predominant form in plasma suggests that the enkephalin-endorphin opiate peptides, which are contained in the "missing" 59-91 sequence from the betaLPH precursor of lambdaLPH, may be secreted in parallel with ACTH under both physiological and pathological conditions in man.

Synthesis of leucine enkephalin derivatives: Structure-function studies

The solid phase synthesis of highly purified [Leu 5] enkephalin and of seven derivatives including [Ala 2,Leu 5]-, [Ser 2,Leu 5]-, [Ser 3,Leu 5]-, [Aba 2,Leu 5]-, and [des-Gly 2(3),Leu 5]enkephalins are reported, and their morphine-like activities in neuroblastoma x glioma cell homogenates were measured. Changes at the 2, 3, and 5 positions of the enkephalin provided analogues which were all less active than [Leu 5] enkephalin. The results are discussed in terms of recently suggested conformational structures for the enkephalin peptides. No melanocyte stimulating activity was observed for [Leu 5] enkephalin, [Ala 2,Leu 5]enkephalin, or [Ser 2,Leu 5] enkephalin.

INVESTIGATION OF THE ROLE OF TRYPTOPHAN IN α‐MSH*:

Two analogues of alpha-MSH are described, in which the tryptophan residue occuring in position 9 of the natural hormone has been replaced by pentamethylphenylalanine and phenylalanine, respectively. The analogues were synthesized via a conventional procedure and the [Phe9]-analogue also by a semi-synthetic approach, which demonstrated the favourable properties of the applied, new amino-protecting Msc function for this purpose. The widely different electron donor properties of the substituted residues were accompanied by a large difference in melanocyte stimulating activity of the analogues. The [Pmp9]-analogue, having donor properties comparable to those of the natural compound, was four to five times more active than the analogue containing the poorly donating Phe residue. The opposite effect was noted in in vivo lipolysis in rabbits.

Small peptides with melanocyte-stimulating activity

FEBS LettersVolume 67, Issue 1 p. 45-47 Full-length articleFree Access Small peptides with melanocyte-stimulating activity K. Medzihradszky, K. Medzihradszky Institute of Organic Chemistry, Eötvös University, Budapest H-1088 Budapest, Muzeum krt. 4, HungarySearch for more papers by this authorH. Medzihradszky-Schweiger, H. Medzihradszky-Schweiger Institute of Organic Chemistry, Eötvös University, Budapest H-1088 Budapest, Muzeum krt. 4, HungarySearch for more papers by this author K. Medzihradszky, K. Medzihradszky Institute of Organic Chemistry, Eötvös University, Budapest H-1088 Budapest, Muzeum krt. 4, HungarySearch for more papers by this authorH. Medzihradszky-Schweiger, H. Medzihradszky-Schweiger Institute of Organic Chemistry, Eötvös University, Budapest H-1088 Budapest, Muzeum krt. 4, HungarySearch for more papers by this author First published: August 01, 1976 https://doi.org/10.1016/0014-5793(76)80867-8Citations: 11AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. References 1 H. Otsuka, K. Inouye, Bull. Chem. Soc. Japan, 37, (1964), 1465– 1471. 2 A. Eberle, R. Schwyzer, Helv. Chim. Acta, 58, (1975), 1528– 1535. 3 J. Hughes, T.W. Smith, H.W. Kosterlitz, L.A. Fothergill, B.A. Morgan, H.R. Morris, Nature, 258, (1975), 577– 579. 4 K. Shizume, A.B. Lerner, T.B. Fitzpatrick, Endocrinology, 54, (1954), 553– 560. 5 T.H. Lee, A.B. Lerner, J. Biol. Chem., 221, (1956), 943– 959. 6 C.H. Li, B. Gorup, D. Chung, J. Ramachandran, J. Org. Chem., 28, (1963), 178– 181. Citing Literature Volume67, Issue1August 01, 1976Pages 45-47 ReferencesRelatedInformation

Comparison of the steroidogenic and melanotropic activities of corticotropin, α-melanotropin and analogs with their lipolytic activities in rat and rabbit adipocytes

The ability of α-melanotropin and a series of synthetic peptides related to adrenocorticotropin (ACTH) to stimulate steroidogenesis in isolated rat adrenal cells, melanin dispersion in frog melanophores and lipolysis in rat and rabbit fat cells have been studied. It was found that the steroidogenic activity closely paralleled the lipolytic activity of these peptides in rat fat cells, whereas the melanocyte stimulating activity paralleled the lipolytic activity in rabbit fat cells. These results indicate that the structural requirements for stimulating steroidogenesis in isolated rat adrenal cells and lipolysis in isolated rat fat cells are quite similar. The structural features required for wliciting lipolysis in rabbit fat cells appear to be very similar to those necessary for stimulating frog melanophores. The possibility that regulation of lipid metabolism in the rabbit may be a new function acquired ny melanotropin is discussed.

Synthesis and biological activity of camel and bovine beta-melanotropins.

Two natural occurring melanotropins, camel betaC2-MSH and bovine beta-MSH, have been synthesized by improved solid-phase procedures. The coupling reaction of tert-butyloxycarbonylamino acids was achieved by using their preformed symmetrical anhydrides. The synthetic hormones were purified by gel filtration on Sephadex G-10 and G-25, chromatography on carboxymehtylcellulose, and partition chromatography on Sephadex G-25 with final yields of 56 and 35% for betac2-MSH and betab-MSH, respectively. They were then shown to be identical with their natural hormones in amino acid analysis, paper electrophoresis, disc electrophoresis, thin-layer chromatography, enzymic digests, and bioassays. Bioassay data of these two synthetic melanotropins indicate that the replacement of Ser by Gly in betab-MSH does not change its melanocyte-stimulating activity.

Depressor effect of synthetic peptides related to ACTH on blood pressure in rats

The depressor effects of natural and synthetic ACTH peptides were demonstrated in the rat. This is an extra-adrenal action of ACTH and is not related to the adrenal-stimulating or melanocyte-stimulating activity of the peptide.

Structure-activity relationships of adrenocorticotropin

Since the entire amino acid sequence of the adrenocort icotropin (adrenocort icotropic hormone, ACTH) from pig pituitaries was proposed (Bell, 1954; Shepherd et al., 1956b), a number of f ragments and analogues of A C T H have been synthesized and submitted to biological characterization. Concurrent with the remarkable advances in the field of peptide chemistry, the synthetic approach to the understanding of the s t ructure-act ivi ty relationships of polypeptide hormones has made a considerable progress during the last decade. Such studies are of great importance not only f rom a fundamental but also f rom a practical point of view, especially in connection with the problem of designing analogues which have some advantage over the natural hormones. A C T H is one of those peptides which have received the most extensive investigations along this line. In an a t tempt to review the recent investigations on the structure and function of A C T H in this article our attention is focused on the synthetic studies, which have enabled us to see the effect of the chain length and structural alteration of the hormone molecule on the ability to stimulate the adrenal steroidogenesis which is regarded as the major role of ACTH. Among some extra-adrenal activities exhibited by ACTH, only the melanocyte-st imulat ing activity will be mentioned briefly as a function of the structure of ACTH. For additional information the reader is referred to the excellent reviews and articles in which the subject is treated thoroughly or adequately (Hofmann, 1962; Hofmann and Yajima, 1962b; Lebovi tz and Engel, 1964; Li, 1962; Ramachandran and Li, 1967; Ramachandran, 1973; Schr6der and LiJbke, 1966; Schwyzer, 1963, 1964).

Isolation of a Tridecapeptide from Natriuretic Fractions of Bovine Posterior Pituitary

Abstract. Crude Van Dyke protein prepared from frozen bovine posterior pituitary glands was treated with formic acid to release small bound and adsorbed peptides. Gel filtration, continuous free‐flow electrophoresis and descending paper electrophoresis were used to separate the small peptides into successively purer fractions which were assayed for pressor, uterotonic, natriuretic and melanocyte stimulating activities under double blind conditions. The highest peak of natriuretic activity was associated with only a small pressor and no uterotonic activities, and the same fractions contained a ninhydrin‐positive spot on paper electrophoresis, the mobility of which at pH 5.6 was similar to that of alpha‐melanocyte stimulating hormone (MSH) and ACTH‐(1–13‐amide)‐tri‐decapeptide (1–13 ACTH‐amide) but differed from vasopressin and oxytocin. Material from this spot had an amino acid composition which corresponded with the first 13 residues of ACTH. Quantitative bioassay of the final fraction in the frog demonstrated a melanotropic activity which, however, was lower than would have been expected for pure alpha‐MSH. The natriuretic activity of the isolated fraction was far higher than the potency of separately administered peptides which might be present: arginine‐vasopressin, alpha‐MSH or 1–13 ACTH. It is suggested that the isolated fraction represents a mixture of alpha‐MSH and 1–13 ACTH, and that alpha‐MSH may be an acetylated end‐product of ACTH cleavage in the pituitary.