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At least 739 records · Page 41Linked to original sources
PubMed1995

Electromyographic and neuromuscular variables in post-polio subjects.

OBJECTIVE: Post-polio subjects experience functional deterioration many years after developing acute poliomyelitis and have been shown previously to have a deficit in strength recovery after isometric activity. This study characterized the size and stability of the motor units in a group of post-polio subjects with macro and single fiber electromyography (EMG) and correlated these variables with isometric strength, endurance, "work capacity," and strength recovery after fatiguing isometric exercise. DESIGN: A cohort of 12 post-polio subjects was tested for neuromuscular function. Electromyographic variables were determined on a separate day. SETTING: Volunteers were recruited from the community and tested in our neuromuscular research laboratory. SUBJECTS: A volunteer sample was obtained from advertisements. All subjects acknowledged post-polio syndrome symptoms. MAIN OUTCOME MEASURES: Neuromuscular variables were isometric knee extension peak torque, endurance (time to exhaustion) at 40% of maximal torque, tension time index, and recovery of torque at 10 minutes. Electromyographic variables were macro EMG and single fiber EMG (percent blocking and jitter). RESULTS: Macro EMG amplitude was ninefold the control value, and both jitter and blocking were greatly increased in comparison to control values. Isometric strength significantly (p < .05) correlated negatively with macro EMG amplitude. CONCLUSIONS: The weakest subjects had the greatest number of muscle fibers within the motor unit (as measured by macro EMG amplitude). Jitter and blocking did not correlate with neuromuscular function.

Adult↗
PubMed2002

Characterisation of cyclic nucleotide phosphodiesterase isoforms in the media layer of the main pulmonary artery.

Cyclic nucleotides are involved in the control of pulmonary vascular tone. In the present study, we measured the cyclic nucleotide specific phosphodiesterase (PDE) activity in the media of bovine isolated main pulmonary artery (MPA). Total cAMP- and cGMP-PDE activities were measured in microsomal and cytosolic fractions. Both cyclic nucleotides were hydrolysed in these subcellular fractions at consistently higher rate in the cytosolic than in the microsomal fraction. Using different classes of PDE modulator, at least four PDE isoforms (PDE1, 3, 4 and 5) were identified in these fractions. PDE3 (cilostamide-sensitive), PDE4 (rolipram-sensitive) and PDE5 (zaprinast- and DMPPO-sensitive) isoforms appeared as the main isozymes implicated in the cAMP and cGMP hydrolytic activities. Calcium-camodulin stimulated PDE activity (PDE1) was mainly present in the cytosolic fraction. PDE2, although present, had a lower hydrolytic activity since addition of its specific inhibitor, erythro-9-(2-hydroxy-3nonyl)adenine (EHNA), to a combination of inhibitors of PDE3, 4 and 5 produced no further significant reduction in the enzymatic activity. Resolution of PDE activities from the cytosolic fraction using anion exchange chromatography confirmed this finding. Functional experiments performed in endothelium-denuded rings of rat MPA revealed that all specific PDE inhibitors used relaxed precontracted vascular smooth muscle preparations in a concentration-dependent manner. The rank order of potency was cilostamide >zaprinast>rolipram>>EHNA. The present study demonstrates the presence in the smooth muscle cells-containing layer of MPA of PDE1, 3, 4 and 5 isoforms and suggests that PDE3, 4 and 5 are the main enzymes involved in the control of vascular tone.

1-Methyl-3-isobutylxanthine↗
PubMed2003

Ionic mechanisms underlying spontaneous CA1 neuronal firing in Ca2+-free solution.

Hippocampal CA1 neurons exposed to zero-[Ca(2+)] solutions can generate periodic spontaneous synchronized activity in the absence of synaptic function. Experiments using hippocampal slices showed that, after exposure to zero-[Ca(2+)](0) solution, CA1 pyramidal cells depolarized 5-10 mV and started firing spontaneous action potentials. Spontaneous single neuron activity appeared in singlets or was grouped into bursts of two or three action potentials. A 16-compartment, 23-variable cable model of a CA1 pyramidal neuron was developed to study mechanisms of spontaneous neuronal bursting in a calcium-free extracellular solution. In the model, five active currents (a fast sodium current, a persistent sodium current, an A-type transient potassium current, a delayed rectifier potassium current, and a muscarinic potassium current) are included in the somatic compartment. The model simulates the spontaneous bursting behavior of neurons in calcium-free solutions. The mechanisms underlying several aspects of bursting are studied, including the generation of triplet bursts, spike duration, burst termination, after-depolarization behavior, and the prolonged inactive period between bursts. We show that the small persistent sodium current can play a key role in spontaneous CA1 activity in zero-calcium solutions. In particular, it is necessary for the generation of an after-depolarizing potential and prolongs both individual bursts and the interburst interval.

Action Potentials↗
PubMed2003

Central nuclei mediating estrogen-induced changes in autonomic tone and baroreceptor reflex in male rats.

The current investigation examines the significance of estrogen in central cardiovascular regulatory nuclei in modulating autonomic tone and baroreceptor reflex function. Experiments were done in anaesthetized male Sprague-Dawley rats. Changes in autonomic tone were assessed by monitoring vagal and renal efferent nerve activities before and following bilateral injection of estrogen into select central autonomic nuclei. In the first study, selective blockade of neurotransmission through the central nucleus of the amygdala (CNA), lateral hypothalamic area (LHA) and ventral posteromedial thalamic nucleus (VPM) using the local anaesthetic lidocaine was done to determine which nuclei were involved in mediating the autonomic changes observed following bilateral injections of estrogen into the insular cortex (IC). In the second study, the role of the parabrachial nucleus (PBN) in mediating the autonomic changes observed following bilateral estrogen injections into the CNA, LHA, VPM and IC was determined by blocking neurotransmission through the PBN using lidocaine.Injections of estrogen into the IC produced a significant increase in renal sympathetic nerve activity (RSNA; from 10+/-2 to 24+/-4 microV/sec; p<0.05). This estrogen-induced increase in RSNA was significantly attenuated when lidocaine was pre-injected into the LHA, CNA or PBN (55+/-6, 33+/-4 and 91+/-7% decrease respectively; p<0.05) but not when injected into the VPM (16+/-6% decrease; p>0.05). Injection of estrogen into the CNA resulted in a significant decrease in RSNA (48+/-5%; p<0.05) whereas estrogen injection into the LHA resulted in a significant increase (28+/-4%; p<0.05) in RSNA. Pre-injection of lidocaine into the PBN resulted in complete blockade of the autonomic changes observed following estrogen injection into the CNA but did not affect the changes observed following estrogen injection into the LHA. These results suggest that estrogen acting in forebrain and midbrain cardiovascular nuclei activated efferent pathways which synapse in the LHA, CNA and/or PBN prior to projecting to autonomic preganglionic nuclei to affect autonomic tone. These nuclei may therefore provide an added level of processing and/or integration of the autonomic response(s) following activation by local or systemic estrogen.

Amygdala↗
PubMed2003

Adenohypophysis formation in the zebrafish and its dependence on sonic hedgehog.

Formation of the adenohypophysis in mammalian embryos occurs via an invagination of the oral ectoderm to form Rathke's pouch, which becomes exposed to opposing dorsoventral gradients of signaling proteins governing specification of the different hormone-producing pituitary cell types. One signal promoting pituitary cell proliferation and differentiation to ventral cell types is Sonic hedgehog (Shh) from the oral ectoderm. To study pituitary formation and patterning in zebrafish, we cloned four cDNAs encoding different pituitary hormones, prolactin (prl), proopiomelancortin (pomc), thyroid stimulating hormone (tsh), and growth hormone (gh), and analyzed their expression patterns relative to that of the pituitary marker lim3. prl and pomc start to be expressed at the lateral edges of the lim3 expression domain, before pituitary cells move into the head. This indicates that patterning of the pituitary anlage and terminal differentiation of pituitary cells starts while cells are still organized in a placodal fashion at the anterior edge of the developing brain. Following the expression pattern of prl and pomc during development, we show that no pituitary-specific invagination equivalent to Rathke's pouch formation takes place. Rather, pituitary cells move inwards together with stomodeal cells during oral cavity formation, with medial cells of the placode ending up posterior and lateral cells ending up anterior, resulting in an anterior-posterior, rather than a dorsoventral, patterning of the adenohypophysis. Carrying out loss- and gain-of-function experiments, we show that Shh from the ventral diencephalon plays a crucial role during induction, patterning, and growth of the zebrafish adenohypophysis. The phenotypes are very similar to those obtained upon pituitary-specific inactivation or overexpression of Shh in mouse embryo, suggesting that the role of Shh during pituitary development has been largely conserved between fish and mice, despite the different modes of pituitary formation in the two vertebrate classes.

Amino Acid Sequence↗
PubMed2003

The Hox gene Ultrabithorax modulates the shape and size of the third leg of Drosophila by influencing diverse mechanisms.

The developmental mechanisms that regulate the relative size and shape of organs have remained obscure despite almost a century of interest in the problem and the fact that changes in relative size represent the dominant mode of evolutionary change. Here, I investigate how the Hox gene Ultrabithorax (Ubx) instructs the legs on the third thoracic segment of Drosophila melanogaster to develop with a different size and shape from the legs on the second thoracic segment. Through loss-of-function and gain-of-function experiments, I demonstrate that different segments of the leg, the femur and the first tarsal segment, and even different regions of the femur, regulate their size in response to Ubx expression through qualitatively different mechanisms. In some regions, Ubx acts autonomously to specify shape and size, whereas in other regions, Ubx influences size through nonautonomous mechanisms. Loss of Ubx autonomously reduces cell size in the T3 femur, but this reduction seems to be partially compensated by an increase in cell numbers, so that it is unclear what effect cell size and number directly have on femur size. Loss of Ubx has both autonomous and nonautonomous effects on cell number in different regions of the basitarsus, but again there is not a strong correlation between cell size or number and organ size. Total organ size appears to be regulated through mechanisms that operate at the level of the entire leg segment (femur or basitarsus) relatively independently of the behavior of individual subpopulations of cells within the segment.

Animals↗
PubMed2003

Sox10 is required for the early development of the prospective neural crest in Xenopus embryos.

The Sox family of transcription factors has been implicated in the development of different tissues during embryogenesis. Several mutations in humans, mice, and zebrafish have shown that depletion of Sox10 activity produces defects in the development of neural crest derivatives, such as melanocytes, ganglia of the peripheral nervous system, and some specific cell types as glia. We have isolated the Xenopus homologue of the Sox10 gene. It is expressed in prospective neural crest and otic placode regions from the earliest stages of neural crest specification and in migrating cranial and trunk neural crest cells. Loss-of-function experiments using morpholino antisense oligos against Sox10 produce a loss of neural crest precursors and an enlargement of the surrounding neural plate and epidermis. This effect of Sox10 depletion is produced during some of the earliest steps of neural crest specification, as is shown by the inhibition in the expression of Slug and FoxD3, which are early markers of neural crest specification. In addition, we show that Sox10 depletion leads to an increase in apoptosis and a decrease in cell proliferation in the neural folds, suggesting that Sox10 could work as a survival as well as a specification factor in neural crest precursors during premigratory stages. Although some of the deficiencies found in the Waardenburg syndrome and in the Hirschprung disease could be associated with a failure of the development of crest derivatives during the late phase of its development, or even during adulthood, our results suggest that inhibition of Sox10 activity produces an earlier failure of neural crest precursors. In experiments where melanocytes and ganglia were induced in vivo and in vitro, we were able to block their development by inhibiting Sox10 activity. These results are compatible with an additional late role of Sox10 on development of neural crest derivatives, as it has been previously proposed. We show that Sox10 expression is dependent on FGF and Wnt activity, both in the neural crest and in the otic placode territories. Finally, in order to establish the position of Sox10 in the hierarchical cascade of gene activation required for neural crest specification, we used inducible forms of the wild type and dominant negatives for the Snail and Slug genes. Our results show that Snail is able to control Sox10 expression. However, the overexpression of Slug was not able to upregulate Sox10 expression. Taken together, these results indicate that Sox10 may lie between Snail and Slug in the genetic cascade that controls neural crest development.

Amino Acid Sequence↗
PubMed2003

ATF-2 cooperates with Smad3 to mediate TGF-beta effects on chondrocyte maturation.

This study demonstrates that ATF-2 cooperates with Smad3 to regulate the rate of chondrocyte maturation in response to TGF-beta. ATF-2 was rapidly phosphorylated in chick embryonic cephalic sternal chondrocytes following treatment with TGF-beta, and the effect was dependent upon p38 kinase activity. Transient transfection of both wild-type ATF-2 or Smad3 activated the TGF-beta-responsive reporter, p3TP-Lux, and synergistic effects were observed with ATF-2 and Smad3 coexpression. The effect of Smad3 and ATF-2 alone and in combination on chondrocyte maturation was examined in cultures simultaneously infected with RCAS viruses expressing different viral envelope proteins. When expressed alone, wild-type ATF-2 or Smad3 both inhibit colX expression and partially mimic the effects of exogenous TGF-beta. However, in combination the effects were additive and similar to the inhibitory effects of TGF-beta on colX expression. Loss of function experiments using dominant negative ATF-2 or Smad3 partially blocked the inhibitory effect of TGF-beta on colX, while together the blockade was complete. Similar effects were observed with another TGF-beta-responsive gene, PTHrP. However, the induction of colX by BMP-2 was not affected by overexpression of either wild-type or dominant negative ATF-2, indicating specificity for TGF-beta signaling. In contrast, although TGF-beta does not activate CRE/CREB signaling, dominant negative CREB enhanced colX expression in control and in TGF-beta and BMP-2-treated cultures. Thus, ATF-2 regulates chondrocyte maturation as a direct target of TGF-beta signaling while CREB regulates differentiation by targeting genes independent of the individual signaling effects of TGF-beta or BMP-2.

Activating Transcription Factor 2↗
PubMed1999

A 69 bp fragment in the pyrroline-5-carboxylate reductase promoter of Arabidopsis thaliana activates minimal CaMV 35S promoter in a tissue-specific manner.

The Arabidopsis thaliana gene that encodes pyrroline-5-carboxylate reductase (At-P5R), the last enzyme in proline biosynthesis in A. thaliana, is developmentally regulated and is highly expressed in cells that divide rapidly or undergo changes in osmotic potential. A 69 bp region (P69; -120 to -51) has previously been identified in a 5' deletion analysis of the At-P5R promoter to be necessary for the basal expression. Here, the essential role of P69 for tissue-specific expression of At-P5R is demonstrated by loss- and gain-of-function experiments.

Arabidopsis↗
PubMed1987

Analysis of vesicle immunolysis assays. The direct binding model.

Assays based on lysis of lipid vesicles have shown high sensitivity. However, little as yet is known about the quantitative relationships among the various assay parameters, due in part to the lack of a predictive theoretical model. This paper presents the derivation of the equations that describe a simple model assay system in terms of the total fraction of vesicles with bound antibodies and the distribution of vesicles with one, two, or more antibodies bound. The equations show how the binding of antibodies to vesicles is affected by such variables as: vesicle concentration, antigen density on vesicle surfaces, antibody concentration, and antibody affinity. With the distribution functions, experiments can be designed to determine the minimum number of antibodies needed to lyse a vesicle. In addition, it is shown how estimations of the ultimate sensitivity of lipid vesicle lytic assays can be made. The model can be used to optimize vesicle lysis assay systems.

Antigen-Antibody Reactions↗
PubMed1996

Tissue concentrations of endothelins and functional effects of endothelin-receptor activation in human arteries and veins.

In the present study, the tissue content and functional effects of endothelin-1 and endothelin-3 were examined in human vessels of importance in coronary bypass operations. Human coronary arteries (i.e., the left anterior descending coronary artery) were obtained from eight cardiac valve donors within 6 hours after death, pulmonary arteries were perioperatively obtained from 15 patients operated on because of lung tumors, and internal thoracic arteries and great saphenous and cephalic veins were obtained at coronary bypass operations from a total of 28 patients. Endothelin-1 and endothelin-3 content was quantified by radioimmunoassay. For functional experiments, the vessels were mounted in organ baths for recordings of isometric contractions in response to endothelin-1, endothelin-3, and the endothelinA-receptor agonist sarafotoxin 6c. In all vessels investigated, the endothelin-1 content was higher than that of endothelin-3. The highest levels were found in the left anterior descending coronary artery, followed in declining order by the internal thoracic artery, pulmonary artery, saphenous vein, and cephalic vein. Endothelin-1 contracted all vessels in a concentration-dependent fashion. This effect was enhanced in the left anterior descending and internal thoracic arteries by inhibition of nitric oxide and prostaglandin formation. The contractile effect was attenuated in a concentration-dependent fashion in all vessels by incubation with the endothelinA-receptor blocker BQ-123. Furthermore, contractions evoked by endothelin-1 in the left anterior descending coronary and pulmonary arteries were antagonized by the combined endothelinA- and endothelinB-receptor blocker bosentan. Endothelin-3 contracted the left anterior descending coronary and pulmonary arteries and the saphenous vein, but not the internal thoracic artery, in a BQ-123-sensitive fashion. However, after inhibition with nitric oxide or prostaglandin, endothelin-3 also contracted the internal thoracic artery, and the response in the left anterior descending coronary artery was enhanced. Sarafotoxin 6c evoked a BQ-123-sensitive contraction of the left anterior descending coronary artery. It is concluded that endothelinA receptors mediate the major portion of the vasoconstriction observed on exposure to endothelin-1, endothelin-3, and sarafotoxin 6c in the left anterior descending coronary, pulmonary, and internal thoracic arteries and the saphenous vein. Furthermore, endothelinB-receptor activation, with subsequent formation of nitric oxide or prostaglandin (or both), counteracts the vasoconstrictor response to endothelin in the left anterior descending coronary and internal thoracic arteries, but not in the pulmonary artery or saphenous vein. The present findings therefore suggest that endothelinA-receptor antagonism might prove beneficial in preventing possible endothelin-induced coronary graft spasm.

Adult↗
PubMed1999

Synthesis and bioactivity of fatty acid-conjugated GnRH derivatives.

Transdermal delivery of peptidic drugs is usually inefficient, notably due to their hydrophilic character which makes it difficult to cross the hydrophobic layers of the skin. In order to obtain transdermally deliverable analogs of gonadotropin releasing hormone (GnRH), we have synthesized related hydrophobic derivatives by attaching various aliphatic acids to the N(epsilon)-amino side chain of [D-Lys]6GnRH, a superactive GnRH agonist. It was found that the affinity toward the GnRH receptor gradually decrease with increased hydrophobicity, i.e. increase in chain length of the attached aliphatic acid. Nevertheless, analogs with 12-carbon or shorter aliphatic acids were shown to be GnRH superagonists, with in vitro and in vivo potencies similar to that of [D-Lys]6GnRH. [D-Lys-lauryl]6GnRH was shown to have a longer duration of action in vivo, as compared to [D-Lys]6GnRH. The transdermal penetration of the peptides was evaluated by in vivo functional experiments in rats. According to these studies the efficiency of penetration is gradually lowered in increasingly hydrophobic analogs. These results are discussed with respect to the circular dichroism spectra of the peptides in trifluoroethanol. The spectra of the aliphatic acid-conjugated superagonists examined do not express a significant tendency towards a beta-turn conformation, typical of GnRH and its agonists. This finding contradict previous publications which suggested a correlation between the conformations of GnRH analogs in trifluoroethanol and their biological activities.

Administration, Cutaneous↗
PubMedDate not supplied

Oxidative energy metabolism in equine tendon cells.

Hypoxia has been suggested as a possible cause of tissue degeneration and subsequent rupture in equine tendons. To determine whether low oxygen tension is likely to be detrimental to tendon cell function, experiments were designed to investigate oxidative energy metabolism in freshly isolated and cultured equine tendon cells. Freshly isolated tenocytes and cultured fibroblasts possessed activities of the mitochondrial enzyme citrate synthase similar to those of other mammalian cells, with well defined oxidative metabolism. D-[6(-14)C]-glucose oxidation was measurable in both freshly isolated and explant-derived cells. The content of adenosine triphosphate (ATP) in cultured cells was decreased by incubation with a mitochondrial respiratory uncoupler. These data demonstrate that tendon cells are capable of oxidative energy metabolism and rely upon it to maintain cellular ATP levels. Hypoxia must therefore be considered as a possible factor leading to tendon degeneration and subsequent injury.

Adenosine Diphosphate↗
PubMed1998

What can toxins tell us for drug discovery?

Toxins are of interest in drug design because the toxins provide three-dimensional templates for creating small molecular mimics with interesting pharmacological properties. Toxins are also useful in drug discovery because they can be used as pharmacological tools to uncover potential therapeutic targets. With their high potency and selectivity, toxins are often more useful in functional experiments than standard pharmacological agents. We have used two groups of neurotoxins, the dendrotoxins and the muscarinic toxins (MTs), to explore the involvement of subtypes of potassium ion channels and muscarinic receptors, respectively, in processes involved in cognition and the changes in neuronal properties with aging. From our current work, quantitative autoradiographic studies with radiolabelled dendrotoxins reveal widespread distribution of binding sites throughout rat brain sections, but few differences exist between young adult and aged rats. However, displacement studies with toxin K, which preferentially binds to the Kv1.1 subtype of cloned potassium channel, show the selective loss of such sites in regions of the hippocampus and septohippocampal pathway with aging. MTs have been tested for effects on performance of rats in memory paradigms. MT2, which activates m1 receptors, improves performance of rats in a step-down inhibitory avoidance test, whereas MT3, which blocks m4 receptors, decreases performance when given into the hippocampus. This is the first clear demonstration of a role for m4 muscarinic receptors in cognition.

Animals↗
PubMed2000

Intensity fluctuations of ultrasonic scattering in a highly turbulent flow.

Aspects of ultrasound intensity fluctuations backscattered from additive microstructures in a turbulent flow have been investigated theoretically and experimentally for the conditions of a small insonified volume, a high sound frequency and strong turbulence. These conditions are typically found in high resolution Doppler sonar applications. An easily applicable expression for the auto-correlation of scattering intensity fluctuations is obtained by introducing open-channel turbulence theory, a semi-empirical scalar spectrum (including a Batchelor spectrum) and a Gaussian window function. Experiments carried out in a laboratory-clear water, open-channel flow for different turbulence levels verify the underlying assumptions. A good agreement is found with the predictions made with the above-derived expression. The feasibility of extracting flow information from the backscattered intensity fluctuations is discussed.

Acoustics↗
PubMed2005

Is the cerebellum ready for navigation?

Spatial navigation required the acquisition of at least two complementary processes: the organization of the spatial representation of the environment (declarative learning) and the acquisition of a motor behaviour adapted to the specific context (procedural learning). The potential role of the cerebellum in spatial navigation is part of the debate concerning its role in cognitive function. Experiments ranging from cerebellar patients to animal models have indicated that cerebellar damage affects the processing of spatial information. The main unresolved issue concern the interpretation of these deficits. Is the cerebellum involved in both declarative and procedural components of navigation? Could all deficits in navigation paradigms be interpreted by a deficit in a motor-dependant process? The purpose of this review is to examine different results coming from anatomical data, experimental paradigms and models in order to give a critical answer to this question.

Animals↗
PubMed1998

Spatially restricted activation of the SAX receptor by SCW modulates DPP/TKV signaling in Drosophila dorsal-ventral patterning.

Dorsal-ventral patterning within the embryonic ectoderm of Drosophila requires two TGFbeta ligands, DPP and SCW, and two type I TGFbeta receptors, TKV and SAX. In embryos lacking dpp signaling, increasing the level of TKV activity promotes progressively more dorsal cell types, while activation of SAX alone has no phenotypic consequences. However, SAX activity synergizes with TKV activity to promote dorsal development. Functional experiments suggest the two receptors have different ligands: DPP acts through TKV, and SCW acts through SAX. Furthermore, SOG, a negative regulator of this patterning process, preferentially blocks SCW activity. We propose that spatial regulation of the SAX pathway modulates TKV signaling to create positional information over the embryonic ectoderm.

Animals↗
PubMed2001

A pituitary cell-restricted T box factor, Tpit, activates POMC transcription in cooperation with Pitx homeoproteins.

The pituitary gland has provided unique insight into molecular mechanisms and regulatory factors controlling both differentiation and gene transcription. We identified Tpit, a novel T box factor only present in the two pituitary POMC-expressing lineages, the corticotrophs and melanotrophs, and apparently in no other tissue, including hypothalamic POMC neurons. In pituitary cells, Tpit activation of POMC gene transcription requires cooperation with Pitx1, the two factors binding to contiguous sites within the same regulatory element. In gain-of-function experiments, Tpit induces POMC expression in undifferentiated pituitary cells, indicating that it can initiate differentiation into POMC-expressing lineages. TPIT gene mutations were found in patients with isolated deficiency of pituitary POMC-derived ACTH, in support of an essential role of Tpit for differentiation of the pituitary POMC lineage.

Adrenocorticotropic Hormone↗