Hormones by Anterior Pituitary – Regulation-Function-Uses

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Hormones by Anterior Pituitary

Hormones by Anterior Pituitary – Regulation-Function-Uses

Hormones by Anterior Pituitary

Hormones by Anterior Pituitary

Hormones by Anterior Pituitary is of following types;

What are the 7 hormones of the anterior pituitary gland?

  1. Growth Hormone
  2. Prolactin
  3. Gonadotropins Hormone
  4. Thyroid Stimulating Hormone
  5. Adrenocorticotropic Hormone.

Anterior pituitary (adenohypophysis), the master ductless gland, elaborates variety of necessary regulative hormones.

All of those area unit amide in nature and act at animate thing receptors situated on their target cells.

Their secretion is controlled by the neural structure through cathartic and release-inhibitory hormones that area unit transported via hypothalamus hypophyseal vascular system, and is subjected to feedback inhibition by the hormones of their target glands.

Each adenohypophysis internal secretion is made by a separate cluster of cells, that per their staining characteristic area unit either aciduric or stainability.

The acidophils area unit either somatotropes GH; or lactotropes gonadotropic hormone.

The basophils area unit gonadotropes follicle-stimulating hormone and LH; thyrotropes TSH; and corticotrope-lipotropes hormone.

The latter additionally to hormone conjointly manufacture 2 epidermal cell stimulating hormones (MSHs) and 2 lipotropins, however these area unit in all probability not necessary in man.

1. Growth Hormone (GH) Hormones by Anterior Pituitary

Growth Hormone, it’s a 191 organic compound, single chain amide of Molecular Weight of about 22000.

Physiological functions

GH promotes growth of bones and every one alternative organs by inducement dysplasia. In general, there’s a proportionate increase within the size and mass of all components, however within the absence of gonadotropins, sexual maturation doesn’t happen.

The growth of brain and eye is freelance of GH.

It promotes retention of element, atomic number 20 and alternative tissue constituents: additional substance is made. The positive balance results from redoubled uptake of amino acids by tissues and their synthesis into proteins.

Hormones by Anterior Pituitary

GH promotes utilization of fat and spares carbohydrates: uptake of aldohexose by muscles is reduced whereas its output from liver is enhanced; fat is de-escalated.

GH acts on cell surface JAK-STAT binding supermolecule enzyme receptors that area unit gift on much all cells. (Hormones by Anterior Pituitary).

Binding of 1 GH molecule to the animate thing domain of a GH-receptor diamer ends up in the formation of a ternary advanced that undergoes a conformational modification and activates the living thing domain to accompany living substance JAK-STAT tyrosine-protein enzyme leading to metabolic effects also as regulation of organic phenomenon.

The growth promoting, element retentive and sure metabolic actions of GH area unit exerted indirectly through the elaboration of peptides referred to as Somatomedins or Insulin-like growth factors (mainly IGF-1, conjointly IGF-2) that area unit animate thing mediators of GH response.

Liver is that the major supply of current IGF-1, whereas IGF1 made by alternative target cells acts regionally in an exceedingly paracrine manner. Like internal secretion, IGF-1 promotes lipogenesis and aldohexose uptake by muscles.

The IGF-1 receptor is also structurally and functionally analogous to the internal secretion receptor (see p. 261). GH acts directly also to induce lipolysis in animal tissue, gluconeogenesis and glycogenolysis in liver and diminished aldohexose utilization by muscles.

These effects area unit opposite to those of IGF-1 and internal secretion. As such, GH accentuates the metabolic derangement in polygenic disorder.

Regulation of secretion (Hormones by Anterior Pituitary)

The neural structure produces GH cathartic (GHRH) also as unleash repressing (somatostatin) hormones.

Both area unit peptides. Somatostatin is additionally made by D cells of islets of Langerhans within the duct gland and by few alternative tissues.

Receptors for GHRH and somatostatin area unit G supermolecule coupled receptors (GPCRs) that enhance or inhibit GH secretion by increasing or decreasing cAMP formation severally in pituitary somatotropes. (Hormones by Anterior Pituitary)

Somatostatin has conjointly been shown to inhibit Ca2+ channels and open K+ channels. Stimuli that cause GH unleash area unit fast, hypoglycaemia, exercise, stress and that i.v. infusion of essential amino acid.

GH secretion is strangled by rise in plasma free carboxylic acid levels and by high doses of glucocorticoids.

Anterior Pituitary

Dopaminergic agents cause a quick increase in GH unleash in traditional subjects however paradoxically depress it in acromegalics.

IGF-1 causes feedback inhibition of GH secretion. Short-loop feedback inhibition of secretion by GH itself has conjointly been represented.

Pathological involvements (Hormones by Anterior Pituitary)

Excess production of GH is answerable for gigantism in childhood and hypertrophy in adults.

Hyposecretion of GH in kids ends up in pituitary genetic disorder.

Adult GH deficiency is rare, however once it happens, it ends up in low muscle and bone mass, lethargy, diminished work capability, lipoidaemia and redoubled vas risk.

Preparations and use (Hormones by Anterior Pituitary)

The first indication for GH is pituitary dwarfism—0.03–0.06 mg/kg daily within the evening or on alternate days, up to the age of twenty years or additional.

Human GH made by recombinant deoxyribonucleic acid technique (rhGH) somatropin (191AA) is offered for clinical use. Also check out Bioassay of Insulin.

Somatropin causes IGF-1 to look in plasma when a delay of many hours. IGF-1 then remains detectable for upto forty eight hours.

Early designation and establishment of GH medical care restores stature to close traditional.

rhGH may also be utilized in Turner’s syndrome and in kids with failure.

Somatropin has been tried in kids with constitutional short stature (only if epiphyses area unit open) with encouraging results.

Commercial interests area unit promoting it for fast growth in kids while not GH deficiency, however medical, ethical, cost-benefit and social objections are raised.

In adult GH deficient patients, rHGH 150–300 g/day s.c. adjusted later per response will increase lean body mass, decreases body fat, improves energy and thought and should reudce excess morbidity and mortality, however stature is unaffected.

Benefits of rHGH medical care in GH deficient adults area unit currently well recognized. Unlimited handiness of recombinant GH has provided chance for its trial in catabolic states like severe burns, bedrid patients, chronic failure, pathology, etc.

It is currently approved for AIDS connected wasting: higher dose (0.05–0.1 mg/kg/day) is required.

However, it mustn’t incline to surgical , trauma, cancer and alternative critically sick patients. Somatropin is additionally being promoted for ageing, however edges area unit unsure.

Its abuse by athletes is illegal, and it’s one in all the medication enclosed in ‘dope testing’. Somatropin: NORDITROPIN five, 10, 15 mg inj, HUMATROPE half dozen mg, twelve mg cartridges, 1.33 and 5.33 mg vials.

Adverse effects (Hormones by Anterior Pituitary)

  • Somatropin has low immunogenicity; allergies or resistance to treatment don’t seem to be a haul.
  • Pain at injection, leukodystrophy, aldohexose intolerance, gland disease (due to expose of thyroid-stimulating hormone deficiency), salt and water retention, hand stiffness, myalgia, headache area unit the attainable adverse effects.
  • Rise in intracranial tension happens in few cases.

GH Inhibitors (Hormones by Anterior Pituitary)

  • Somatostatin This fourteen organic compound amide inhibits the secretion of GH, prolactin, and thyroid-stimulating hormone by pituitary; internal secretion and endocrine by duct gland, and of just about all gi secretions as well as that of internal secretion and HCl.
  • The G.I. action produces steatorrhoea, diarrhoea, hypochlorhydria, stomach upset and nausea as facet impact. Somatostatin constricts visceral, viscus and urinary organ blood vessels.
  • The diminished g.i. membrane blood flow is used for dominant trauma muscle system varices and trauma ulceration, however octreotide is preffered currently because of longer period of action. Its antisecretory action is helpful in duct gland, biliary or enteral fistulae; may also be accustomed
  • Reduce complications when duct gland surgery.
  • It conjointly has adjuvant worth in diabetic acidosis (by inhibiting endocrine and GH secretion).
  • Use of somatostatin in hypertrophy is restricted by its short period of action (t½ 2–3 min), lack of specificity for inhibiting solely GH secretion and GH rebound on discontinuance.
  • Surgical removal of pituitary adenomas is that the most popular treatment modality, however somatostatin analogues area unit being progressively used.

Dose: (for higher g.i.bleeding) 250 µg slow i.v. injection over three min followed by three mg i.v. infusion over twelve hours. STILMEN, SOMATOSAN, SOMASTAT 250 µg and three mg amps.

2. PROLACTIN (Hormones by Anterior Pituitary)

It is a 199 organic compound, single chain amide of MW 23000; quite similar with chemicals to GH.

It was originally represented because the internal secretion that causes secretion of milk from crop glands of columbiform bird and later found to be of significant importance in masses also.

Physiological Functions (Hormones by Anterior Pituitary)

Gonadotropin hormone is that the primary input that in conjunction with estrogen, progestin {and several|and a number of alternative|and several other} other hormones, causes growth and development of breast throughout gestation.

It promotes proliferation of ductal also as acinar cells within the breast and induces synthesis of milk proteins and disaccharide.

After birthing, gonadotropic hormone induces milk secretion, since the repressing influence of high steroid hormone and progestin levels is withdrawn.

gonadotropic hormone suppresses hypothalamo-pituitarygonadal axis by inhibiting GnRH unleash.

continuing high level of gonadotropic hormone throughout breastfeeding is answerable for lactational amenorrhea, inhibition of biological process and physiological condition for many months postnatal.

gonadotropic hormone could have an effect on reaction through action on T-lymphocytes. a selected gonadotropic hormone receptor is expressed on the surface of target cells, that is structurally and functionally analogous to GH receptor.

Action is exerted by transmembrane activation of JAK—cytoplasmic amino acid supermolecule kinases and STAT. Placental agent and GH conjointly bind to gonadotropic hormone receptor and exert similar effects, however gonadotropic hormone doesn’t bind to GH receptor.

Regulation of secretion (Hormones by Anterior Pituitary)

gonadotropic hormone is beneath predominant repressing management of neural structure through PRIH that is Intropin that acts on pituitary lactotrope D2 receptor. Dopaminergic agonists (DA, bromocriptine, cabergoline) decrease plasma gonadotropic hormone levels, whereas dopaminergic antagonists (chlorpromazine, major tranquilizer, metoclopramide) and DA depleter (reserpine) cause hyperprolactinemia.

Though TRH, gonadotropic hormone cathartic amide and important person will stimulate gonadotropic hormone secretion, no specific gonadotropic hormone cathartic issue has been known.

Hormones secreted by Anterior Pituitary

Endogenous opioid peptides may additionally be concerned in control gonadotropic hormone secretion, however no feedback regulation by any peripheral internal secretion is understood. gonadotropic hormone levels in blood area unit low in childhood, increase in ladies at pubescence and area unit higher in adult females than in males.

A progressive increase happens throughout gestation, peaking at term. Afterward, high gonadotropic hormone secretion is maintained by suckling: it falls if nursing is discontinued . Stress, labor and hypoglycemia conjointly stimulate gonadotropic hormone unleash.

Physio-pathological involvement (Hormones by Anterior Pituitary)

Hyperprolactinaemia is answerable for the galactorrhoea– amenorrhoea–infertility syndrome in girls.

In males it causes loss of physical attraction and depressed fertility.

The causes of hyperprolactinaemia are:

(i) Disorders of neural structure removing the repressing management over pituitary.

(ii) Antidopaminergic and DA depleting medication —these area unit a frequent cause currently.

(iii) gonadotropic hormone secreting tumours—these is also microprolactinomas or macroprolactinomas.

(iv) gland disease with high thyrotropin-releasing factor levels—also will increase gonadotropic hormone secretion.

Use: There are not any clinical indications for gonadotropin hormone.

Prolactin inhibitors (Hormones by Anterior Pituitary)

a. Bromocriptine

This artificial ergot spinoff spinoff ergocryptine could be a potent Intropin agonist; most of its actions area unit supported this property. it’s larger action on D2 receptors, whereas at sure Intropin sites within the brain it acts as a partial agonist or antagonist of D1 receptor. it’s conjointly a weak  adrenergic blocker however not associate medicine.

Actions

  • 1. Decreases gonadotropic hormone unleash from pituitary by activating dopaminergic receptors on lactotrope cells: could be a robust antigalactopoietic.
  • 2. will increase GH unleash in traditional people, however decreases identical from pituitary tumours that cause hypertrophy.
  • 3. Has Larodopa like actions in CNS-antiparkinsonian and activity effects.
  • 4. Produces nausea and projection by stimulating dopaminergic receptors within the CTZ.
  • 5. Hypotension—due to central suppression of bodily property reflexes and weak peripheral a adrenergic blockade.
  • 6. Decreases channel motility.

Pharmacokinetics (Hormones by Anterior Pituitary)

  • Solely 1/3 of Associate in Nursing oral dose of bromocriptine is absorbed; bioavailability is additional down by high 1st pass metabolism in liver.
  • Even then, it’s higher oral: canal activity quantitative relation than alkaloid. Metabolites area unit excreted chiefly in digestive juice.
  • Its plasma t½ is 3–6 hours.
  • PROCTINAL, PARLODEL, BROMOGEN , SICRIPTIN, 1.25 milligram, 2.5 mg tabs.

Uses

Bromocriptine must always be started at an occasional dose, 1.25 mg baccalaureate and so bit by bit accumulated until response happens otherwise aspect effects become limiting.

1. Hyperprolactinemia due to microprolactinomas inflicting galactorrhoea, amenia and physiological condition in women; gynaecomastia, impotence and sterility in men. Bromocriptine and cabergoline area unit the primary line drug for many cases. comparatively lower doses (bromocriptine two.5–10 mg/day or cabergoline zero.25–1.0 mg doubly weekly) area unit effective.

Response happens in a very few weeks and humour luteotropin levels fall to the conventional range; many ladies conceive.

Bromocriptine ought to be stopped once physiological state happens, although no agent result is according. Most (60–75%) tumours show regression throughout medical aid and medicine symptoms (visual field defects, etc.) thanks to pressure on chiasma ease.

However, response is maintained solely until the drug is given— recurrences occur in several, however not all patients.

2. acromegalia thanks to tiny pituitary tumours and inoperable cases. comparatively higher doses area unit needed (5–20 mg/day) and it’s less effective than octreotide/lanreotide. Oral administration and lower value area unit the benefits.

3. shaking palsy Bromocriptine, if used alone, is effective solely at high doses (20–80 mg/day) that turn out marked aspect effects. However, response is analogous thereto of dopa. it’s currently counseled in low dose solely, as Associate in Nursing adjunct to dopa in patients not adequately benefited and in those showing marked ‘on-off’ result.

4. diabetes (DM) a brand new use of bromocriptine supported its monoamine neurotransmitter D2 agonistic action within the neural structure has been found in sort two DM, Associate in Nursingd it’s been approved by US-FDA as an connected drug.

5. viscus coma: Bromocriptine might cause arousal.

6. Bromocriptine suppresses lactation and breast engorgement just in case of death, however isn’t counselled thanks to unfavourable risk; profit quantitative relation.

Side effects: aspect effects area unit frequent and dose connected. Early: Nausea, vomiting, constipation, nasal blockage. hypotension is also marked at initiation of therapy—syncope might occur if beginning dose is high. cardiovascular disease is additional seemingly in patients taking antihypertensives. Late: activity alterations, state of mind, hallucinations, psychosis—are additional outstanding than with dopa. Abnormal movements, skin condition reticularis.

b. Cabergoline it’s a newer an additional modern an additional recent} D2 agonist; more potent; more D2 selective and longer acting t½ > sixty hours than bromocriptine; has to run solely doubly weekly.

Incidence of nausea and forcing out is additionally lower; some patients not tolerating or not responding to bromocriptine are with success treated with cabergoline.

It’s most well-liked for treatment of hyperprolactinemia and acromegalia. Some patients United Nations agency reach total regression of luteotropinoma and standardization of prolactin levels will stop cabergoline while not repetition.

Dose: begin with zero.25 mg doubly weekly; if required increase when each 4–8 weeks to easy lay. of one mg doubly weekly. CABERLIN 0.5 mg tab, CAMFORTE 0.5, 1 mg tabs.

3. GONADOTROPINS (Gns) (Hormones by Anterior Pituitary)

The ductless gland secretes 2 Gns viz. FSH and LH. each area unit glycoproteins containing 23–28% sugar and carries with it 2 amide chains. The chain (92AA) is common between gonadotrophic hormone and ICSH, however their chains area unit different: gonadotrophic hormone (111 AA), ICSH (121 AA). Paradoxically the MW of gonadotrophic hormone (~33KD) is bigger than that of ICSH (~30 KD), due to the sugar moieties.

Physiological functions

Folical stimulating hormone and leutinizing hormone act mutually to promote gametogenesis and secretion of ductless gland i.e. gonadal hormones.

Folical stimulating hormone (FSH): within the feminine it induces vesicle growth, development of egg cell and secretion of estrogen. Within the male it supports gametogenesis and encompasses a biological process influence on bodily fluid tubules. gonad and male reproductive gland atrophy happens within the absence of Folical stimulating hormone.

Leutinizing hormone (LH): It induces preovulatory swelling of the ripe cyst Graafian follicle and triggers organic process followed by luteinization of the damaged follicle and sustains endocrine gland until ensuing oscillation. It’s additionally most likely answerable for ab normalcy of the remaining follicles.

Progestogen secretion happens solely underneath the influence of ICSH. Within the male luteinizing {hormone|LH|interstitial cell-stimulating hormone|ICSH|gonadotropin|gonadotrophin gonadotropic hormone gonadotrophic hormone} stimulates androgen secretion by the opening cells and is selected opening cell stimulating hormone (ICSH).

Distinct ICSH and gonadotrophic hormone receptors area unit expressed on the target cells. Each area unit G macromolecule coupled receptors that on activation increase cAMP production. This successively stimulates ontogenesis and conversion of steroid alcohol to

pregnenolone-the start in progestogen, androgen and steroid hormone synthesis. Within the testes gonadotrophic hormone receptor is expressed on bodily fluid (Sertoli) cells whereas ICSH receptor is expressed on opening (Leydig) cells.

Within the ovaries gonadotrophic hormone receptors area unit gift solely on granulosa cells, whereas ICSH receptors area unit cosmopolitan on opening cells, theca cells, preovulatory granulosa cells and ductless gland cells.

USES:

  1. Amenorrhoea and infertility.

2. Hypogonadotropic hypogonadism in males.

3. Cryptorchidism.

4. To aid in vitro fertilization.

4. THYROID STIMULATING HORMONE (TSH, THYROTROPIN) (Hormones by Anterior Pituitary)

It’s a 210 amino alkanoic acid, 2 chain compound protein (22% sugar), molecular weight 30000.

Physiological Function

The Thyroid Stimulating Hormone stimulates thyroid to synthesize and secrete tetra iodo thyronine (T4) and liothyronine (T3). its actions are;

  • Induces dysplasia and hypertrophy of thyroid follicles and will increase blood offer to the secretory organ.
  • Promotes caparison of halide into thyroid by increasing Na+: halide symporter (NIS). Promotes organic process of unfree iodine and its incorporation into T3 and T4 by increasing oxidase activity.
  • Enhances endocytotic uptake of thyroid mixture by the cyst cells and chemical action of iodoprotein to unharness additional of T3 and T4.

This action starts among minutes of thyrotrophin administration.

The thyrotrophin receptor gift on thyroid cells could be a GPCR that utilizes the adenylyl cyclase-cAMP electrical device mechanism (by coupling to Gs protein) to provide its effects.

In human thyroid cells high concentration of thyrotrophin conjointly induces PIP2 chemical reaction by the linking of thyrotrophin receptor to Gq supermolecule.

The ensuing increase in cytosolic Ca2+ and supermolecule enzyme C activation may mediate thyrotrophin action, notably generation of H2O2 required for oxidisation of halide and chemical action of tyrosil residues.

Regulation of secretion Synthesis and unharness of thyrotrophin by pituitary is controlled by neural structure primarily through endocrine, whereas somatostatin inhibits thyrotrophin secretion.

monoamine neurotransmitter conjointly reduces thyrotrophin production iatrogenic by endocrine.

The endocrine receptor on pituitary thyrotrope cells could be a GPCR that is coupled to Gq supermolecule and activates PLC–IP3/DAG–cytosolic Ca2+ pathway to reinforce thyrotrophin synthesis and unharness.

The feedback for inhibiting thyrotrophin secretion is provided by the thyroid hormones that act primarily at the extent of the pituitary, however conjointly within the neural structure.

T3 has been shown to scale back endocrine receptors on the thyrotropes. Pathological involvement solely few cases of hypoor glandular disease ar because of inappropriate thyrotrophin secretion.

In majority of cases of myxedema thyrotrophin levels ar markedly elevated thanks to deficient feedback inhibition.

Graves’ sickness is because of associate degree antibody of the immune serum globulin category that attaches to the thyroid cells and stimulates them within the same method as thyrotrophin.

Consequently, thyrotrophin levels ar low. Contrary to earlier belief, thyrotrophin isn’t chargeable for symptom seen in Graves’ sickness as a result of thyrotrophin levels ar low.

Use thyrotropic hormone has no therapeutic use. tetraiodothyronine is that the drug of selection even once glandular disorder is because of thyrotrophin deficiency.

The diagnostic application is to differentiate myxedema because of pituitary pathology from primary thyroid sickness.

Internal secretion (ACTH, CORTICOTROPIN) it’s a thirty-nine aminoalkanoic acid single chain amide, MW 4500, derived from a bigger amide pro-opio melanocortin (MW thirty,000) that conjointly offers rise to endorphins, 2 lipotropins and 2 MSHs.

Physiological Involvement

ACTH promotes steroidogenesis in ductless gland by stimulating cAMP formation in plant tissue cells (through specific cell surface GPCRs) speedily will increase the availability of steroid alcohol for conversion to pregnenolone that is that the rate limiting step within the production of gluco, mineralo and decrepit steroid hormone steroids.

Induction of steroidogenic enzymes happens once a delay leading to ordinal part ACTH action.

The stores of adrenal steroids ar terribly restricted and rate of synthesis primarily governs the speed of unharness. ACTH conjointly exerts biological process influence on ductless gland (again through cAMP): high doses cause hypertrophy and dysplasia.

Lack of ACTH leads to adrenal atrophy. However, zone glomerulosa is no affected as a result of angiotonin conjointly exerts biological process influence on this layer and sustains mineralocorticoid secretion. Regulation of secretion neural structure regulates

5. Adrenocorticotropic Hormone (ACTH, Corticotropin) (Hormones by Anterior Pituitary)

Adrenocorticotropic Hormone is 39 amino acid single chain of peptide, It has molecular weight of about 4500, It is drived from Other longer peptide pro-opio melanocortin which has molecular weight 30,000.

Hormones by Anterior Pituitary

It also give Rise to endorphins, two lipotropins and has 2 MSH’s.

Physiological function acth promotes steroidogenesis in adrenal cortex by means of stimulating camp formation in cortical cells (via precise cellular floor gpcrs) rapidly will increase the availability of ldl cholesterol for conversion to pregnenolone which is the fee proscribing step i the manufacturing of gluco, mineralo and weakly androgenic steroids. Induction of steroidogenic enzymes occurs after a postpone ensuing in second segment acth motion.

The shops of adrenal steroids are very limited and rate of synthesis on the whole governs the price of release. Acth additionally exerts trophic have an impact on adrenal cortex (once more through camp): high doses reason hypertrophy and hyperplasia. Lack of acth consequences in adrenal atrophy.

But, zona glomerulosa is little affected because angiotensin ii additionally exerts trophic have an effect on
On this layer and sustains aldosterone secretion.

Law of secretion hypothalamus regulates acth launch from pituitary via corticotropin-releasing hormone (crh). The crh receptor on corticotropes is likewise a gpcr which will increase acth synthesis in addition to release via raising cytosolic camp.

Secretion of acth has a circadian rhythm. Top plasma levels occur inside the early morning, decrease in the course of day and are lowest in the dark. Corticosteroids exert inhibitory comments have an impact on acth.

Production by way of acting immediately at the pituitary in addition to in a roundabout way via hypothalamus.

A ramification of annoying stimuli, e. G. Trauma, surgical operation, excessive ache, tension, fear, blood loss, exposure to bloodless, etc.

Generate neural impulses which converge on median eminence to purpose elaboration of CRH.

The comments’ inhibition seems to be overpowered throughout stress upward push in ACTH secretion continues notwithstanding excessive plasma degree of cortisol brought about by it.

Arginine vasopressin (AVP) complements the action of CRH on corticotropes and augments ACTHrelease. AVP launch and augmentation of ACTH motion seems to be important at some point of strain.

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