Anterior pitutary hormones
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Transcript of Anterior pitutary hormones
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Anterior pitutary hormones
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Hormone
• Secretory products of endocrine glands released directly into circulation in small amounts and transported to specific target cells or organs where they exert physiological, morphological or biochemical responses
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Types of cell-to-cell signaling
Endocrine Hormones: travel via bloodstream to target cells
Neurocrine hormones: released from nerve terminals
Paracrine hormones: act on adjacent cells
Autocrine hormones: Released and act on the cell that secreted them.
Intracrine Hormones: act within the cell that produces them.
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Classification of hormones
• Depending upon chemical nature – Amines or amino acid derivatives
• Catecholamines, thyroid hormones
– Proteins & polypeptides• Posterior pitutary hormones: oxytocin, vasopressin• Insulin , glucagon, PTH, other anterior pitutary
hormones
– Steroid hormones• Glucocorticoids, mineralocorticoids, sex steroids, Vit D
• Depending on Mechanism of action – Group I & Group II hormones
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Depending on MOA
• Group I: bind to intracellular receptors• Group II: Involve second messenger
– A: cyclic AMP: ACTH, ADH, CRH, FSH, LH,TSH, PTH– B: cyclic GMP: Atrial natriuretic factor, NO– C: calcium/PI: AcH, catecholamines 1, gastrin,
oxytocin, TRH, GnRH – D:kinases/phosphatase: erythropoetin, GH,
insulin, IGF, NGF, prolactin
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Regulation of hormone secretion
• Feed back control – Negative feed back
• Long loop feed back • Short loop feed back • Ultra short loop feed back
– Positive feed back • Neural control • Chronotrophic control
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Negative feed back control
Hypothalamus
Hypophysiotrophic hormone
Anterior pitutary
Pitutary trophic hormone
Target gland
Target gland hormone
Long loop
Short loop
Ultra Short loop
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Negative feedback effects of cortisol
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Feedback control of insulin by glucose concentrations
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Neural control
• Evokes or supresses hormone secretion in response to external & internal stimuli
• External stimuli: visual, auditory, olfactory • Internal stimuli: pain, emotion, fright • Examples of neural control
– Oxytocin : fills milk ducts in response to suckling – Aldosterone: augments circulatory volume in
response to upright posture – Release of melatonin: in response to darkness
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Chronotropic control
• Endogenous neuronal rhythmicity• Diurnal rhythms, circadian rhythms (growth
hormone and cortisol), Sleep-wake cycle; seasonal rhythm
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• frequency of about one hour—circhoral • An episode of release longer than an hour,
but less than 24 hours: ultradian • If the periodicity is approximately 24 hours,
the rhythm is referred to as circadian – usually referred to as diurnal because the
increase in secretory activity happens at a defined period of the day.
Episodic secretion of hormones
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Circadian (chronotropic) control
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Circadian Clock
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Physiological importance of pulsatile hormone release
• Demonstrated by GnRH infusion • If given once hourly, gonadotropin secretion and
gonadal function are maintained normally • A slower frequency won’t maintain gonad
function • Faster, or continuous infusion inhibits
gonadotropin secretion and blocks gonadal steroid production
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Functions of the hormones
• Growth & differentiation • Maintenance of homeostasis • Reproduction• Regulation of biochemical reactions
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Role of hypothalamus
• Highest relay centre • Integrates endocrine & ANS and ensures the
smooth coordination by the cerebral cortex • Hypothalamic regulatory hormones
– Releasing hormones • TRH, GnRH, GHRH,CRH, MSH-RF, Prolactin Releasing
factor
– Releasing inhibitory hormones • GH-RIH, MSH-RIF, PIF
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Anterior pitutary hormones
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Pitutary gland
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Anterior pitutary hormones
• Acidophils: – Somatotrophes: Growth hormone– Lactotrophes: Prolactin
• Basophils:– Gonadotrophes: FSH & LH– Thyrotropes: TSH– Corticolipotrohes: ACTH
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Growth hormone
• 191 amino acid • 22000 molecular weight • Physiological Functions:
– Growth of organs – Positive nitrogen balance – Direct and indirect actions
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Regulation of secretion
• GH Release stimulated by – Dopamine– 5 HT – α2 Agonist
• GH Release inhibited by – IGF-1– Free Fatty Acids– Beta Agonist – GH itself
GHRH & GHIH secreted by hypothalamus
Amplitude of secretory pulses is maximal at night
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Provocative stimuli for GH
• Arginine • Glucagon • L-Dopa• Insulin • Clonidine
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Syndromes associated with GH
• Deficiency of GH – Dwarfism – Increased CVS Mortality
• Excess GH– Gigantism – Acromegaly
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Dwarfism
• Shortness of stature • Growth retardation in all parts of body
proportionately • Normal mental activity • Immature faces • Delicate extremities • Sexual maturity does not occur if associated
with gonadotropin deficiency
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Gigantism
• Abnormal height • Large hands and feet• Coarse facial features • Bilateral gynaecomastia • Loss of libido • Hyperglycemia
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Acromegaly
• Acromegalic face:– thick lips, macroglossia, prominent eye brows– Broad thick nose, thickened skin
• Prognathism – Protrusion of lower jaw
• Spade like hands, thick wide fingers, large feet• Kyphosis • Organomegaly
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Treatment of GH Deficiency
• Cadaveric pitutary growth hormone • Human recombinant preparations
– Somatotropin – Somatotrem – Encapsulated somatotropin – Sermorelin acetate
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Somatropin
• Growth hormone preparation whose sequence matches native growth hormone
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Somatrem
• Derivative of growth hormone with additional methionine at amino terminus
• Somatropin and somatrem have similar biological action and potencies
• Half life = 20 minutes but biological action lasts 9-17 hrs
• Once daily administration is sufficient
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Encapsulated somatropin
• Injected IM once or twice per month
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Sermorelin acetate
• A synthetic form of Human GHRH • Peptide of 29 Aminoacids corresponds to first
29 AA of Human GHRH • Has full biological activity • Well tolerated , Less expensive • But less effective will not work in defects of
anterior pitutary
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Uses of Growth hormone
• Replacement therapy – 20-40 microgram/ kg Subcutaneously daily
• Turners syndrome – 50 microgram/kg
• Aids associated wasting – 3-4 microgram / kg
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Adverse effects
• ↑ ICT with papilloedema • Visual changes• Headache, nausea• Leukemia • ↑ incidence of type 2 DM• Adults:
– Edema, carpal tunnel syndrome, arthralgia, myalgia
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Agents used in GH excess
• Somatostatin • Somatostatin analogs
– Octreotide– Lanreotide – Vapreotide – Sandostatin
• Dopamine receptor agonists: bromocriptine• GH antagonist: Pegvisomant
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Somatostatin
• GHIH• Non specific
– TSH, insulin, gastrin• Half life = 1-3 min• Rebound increase in GH after its
discontinuation • Not preferred
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Octreotide
• More specific for Growth hormone • Less chances of hyperglycemia • Uses
– Carcinoid syndrome – VIP secreting tumors – Gastrinoma – Secretory diarhoea: AIDS, DM– IBS , Esophageal Varices , insulinoma
• Dose: 50 -200 µg TDS subcutaneously
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Sandostatin
• Slow releasing form • 20-40 mg IM 4 weekly • Adverse effects of somatostatin analogs
– Abdominal pain – Steathorrea– GB stone – Vit B12 deficiency
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Prolactin
• 198 Amino acid peptide hormone • Synthesis and secretion starts in fetal pitutary • ↓ Secretion of prolactin by
– Hypothalamic regulation (D2• ↑ secretion of prolactin by
– Stress, exertion, hypoglycemia– TRH, VIP, prolactin releasing peptide
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Regulation of prolactin
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Mechanism of action
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Physiological effects
• Growth & development of breast • Growth and development of ductal and
lobular epithelium • Induce lactation after birth of baby • Increased prolactin levels supress normal
menstrual cycle
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Hyperprolactinemia
• Females:– Galactorrhea and amenorrhoea – Infertility
• Males:– Loss of libido – Infertility
• Drugs causing hyperprolactinemia – Chlorpromazine, haloperidol, metoclopramide– Reserpine , alpha methyl dopa
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Treatment of hyperprolactinemia
• Dopaminergic agonists – Bromocriptine – Cabergoline – Pergolide – Quinagolide
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Bromocriptine
• Uses – Hyperprolactinemia – Acromegaly – Parkinsonism – Hepatic coma – Supression of lactation
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Bromocriptine
• Pharmacokinetics– Only 1/3rd absorbed orally – First pass metabolism present – Half life = 3 hours
• Dose: – Start 1.25 mg HS – After 1 week 1.25 mg can be added in morning – Can be increased to 5 mg BD
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Bromocriptine
• Adverse effects– Nausea , vomiting – Postural hypotension – Nasal decongestion– Digital vasospasm – CNS effects: hallucinations, night mares, insomnia
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Pergolide
• Ergot derivative • Cheapest Dopamine agonist • Dose= 0.025 mg increased to 0.25 mg
gradually
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Cabergoline
• Ergot derivative with longer hlaf life • T ½ = 65 hours • Higher affinity and selectivity to D2 receptors• More effective less toxic • Dose= 0.25 mg twice weekly
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Quinagolide
• Non ergot D2 agonist • T ½ = 22 hours dose= 0.1 -0.5 mg /day
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Gonadotropins (FSH & LH)
• Hypothalamus releases GnRH in pulses 1-2 hrly
• GnRh regulates FSH & LH • Feed back inhibition of LH>FSH• Estrogen & Progesterone inhibit both FSH &
LH • Inhibin inhibits only FSH • Dopamine Inhibits only LH
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Physiological functions
FSH
Females:– Gametogenesis – Follicular development – Estrogen and progesterone
production – Imp role in Menstrual
cycle
Males– Stimulation &
maintainence of spermatogenesis
LH
Females – Ovulation – Corpus luteum
Maintainence – Estrogen & progesterone
production – Imp role in menstrual
cycle Males:
– Testesterone & androgen biosynthesis
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Disturbances of gonadotropin secretion
• Excess– Precocious puberty
• Deficiency – Amenorrhoea, infertility– oligospermia
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Preparations of gonadotropins
• Menotropin: FSH + LH– Obtained from urine of postmenopausal women
• Urofollitropin: Pure FSH – Preferred in PCOD
• HCG– Obtained From Urine Of Pregnant Females
• DNA recombinant FSH
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Uses of gonadotropins
• Infertility in females – When clomiphene fails – Menotropin for 10 days then HCG 10000 IU, IM
• Infertility in males – HCG 1000-2500 IU, IM 3 times in a week – Then menotropin after 3-4 months
• Cryptorchism • To aid Invitro fertilization• Regress AIDS related Kaposis Sarcoma
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Adverse effects
• Ovarian hyperstimulation, multiple pregnancies
• Polycystic ovarian disease • Pain in lower abdomen • Edema, headache, depression• Allergic reactions
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GnRH & GnRH analogs
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Gonadorelin
• Synthetic GnRH • T ½ = 4-6 min • Used for testing pitutary gonadal axis in male
or female hypogonadism • Pulsatile administration IV every 90 min
– Infertility, cryptorchism. & delayed puberty
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GnRH agonists
• Goserelin • Buserilin • Leuprolide • Naferiline • Triptoreline
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GnRH agonists
• Longer acting 6-12 hours • Initial increase in LH & FSH • But after 1-2 weeks cause desensitization and
decrease FSH & LH secretion • Decrease estrogen and testesterone• They cause pharmacological oopherectomy
and orchiectomy
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Uses of GnRH analogs
• Precocious puberty • Prostatic carcinoma • Breast cancer • Contraception: under investigation
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Adverse effects
• Hot flushes • Loss of libido • Vaginal dryness • Osteoporosis • Emotional liability
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GnRH antagonists Cetrorelix , Granirelix
• Competitive antagonists • Advantage
– No initial increase in gonadotropins – Do not cause histamine release
• Used in endometriosis 3 mg Cetrorelix SC weekly for 2 months
• Uterine Fibroids: cetrorelix twice weekly for 1 month before surgery
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Thyroid stimulating hormone
• Stimulates T3 & T4 secretion• Induces hyperplasia and hypertrophy of
thyroid • Promotes oxidation of trapped iodide
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ACTH
• Stimulate cortisol synthesis from adrenal cortex
• Corticotropin Regulating Hormone (CRH): secreted by hypothalamus regulates it.
• USES– Diagnosis of pitutary –adrenal axis disorders – Like corticosteroids but unpredictable action