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Summary Endocrine System and Digestive and Respiratory Tract lectures
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Endocrine system & digestive and respiratory tractIntroduction endocrine system & growth hormones
Martina Schmidt
06/09/2021
The endocrine system is for the autonomic body
functions: functions that are aimed at the continued
existence of the individual and the species.
Communication between organs and cell systems is
important for this: autonomic nervous system,
hormones, interaction between these systems.
Examples of endocrine regulations are: metabolic
functions, function of immune system, internal
environment, reproduction.
Endocrine system: brain, hypothalamus, pituitary
gland > releasing/inhibiting hormones.
Chemical structure and signal transduction mechanisms
Peptide hormone and protein hormones produced in the hypothalamus, pituitary gland, pancreas,
thyroid and parathyroid glands.
Membrane receptors (relatively quick):
- G-protein coupled receptors (adenylyl cyclase, PI metabolism)
- Tyrosine kinases
Steroid hormones, sterols, thyroxine derivatives: adrenal gland reproductive organs, calcitriol (vit D.
derivative), thyroid gland.
Intracellular receptors (relatively slow):
- Regulation of protein synthesis (ligand-gated transcription factors)
Hormones are often analogues, stable agonists/antagonists. With protein hormones (tropic
hormones, parenteral), often more stable effector hormones that can be administered orally
(synthetic steroids, thyroxine derivatives).
Pharmaceuticals affect either hormone synthesis, hormone release, or hormone
metabolism.
Hypothalamic-pituitary system:
Regulate the major part of the endocrine system. Hypothalamus converts nerve
impulses from the brain into a hormone impulse. Pituitary gland is made up of 3
parts: anterior pituitary (anterior lobe), pars intermedia (barely present in humans),
posterior pituitary (posterior lobe). Hormones from the hypothalamus regulate the
release of hormones by the anterior pituitary.
,Hypothalamic-anterior pituitary system Hypothalamic-posterior pituitary system
Hypothalamic hormones:
Transport to the anterior pituitary via the
bloodstream. Regulate the release of anterior
pituitary hormones. Also referred to as
neurohormones because their release is
regulated by neurons. the synthesis of other
hormones by the anterior pituitary is stimulated
(releasing factors RF or hormones RH) or
inhibited (inhibiting factors IF or hormones IH).
The posterior pituitary releases oxytocin and
vasopressin (ADH) directly to the bloodstream.
All hypothalamic hormones are peptides (with
the exception of dopamine).
Anterior pituitary hormones:
- Group 1: Somatotropic hormones
- Group 2: Glycoproteins
- Group 3: Derived from precursor protein (pro-opiomelanocortin)
Group 2: Glycoproteins
Made up of an α-subunit and a β-subunit: LH, FSH, TSH, CG. The α-subunits are virtually identical, and
contain 2 oligosaccharide chains that are bound via asparagine. The β-subunits have the specific
biological effect, and contain 1 or 2 oligosaccharide chains.
Group 3: pro-opiomelanocortin
Multiple hormones are produced from a large precursor molecule by enzymatic cleavage (proteases)
in various tissues. ACTH and β-lipotropin are formed in the anterior pituitary. α-MSH is split off in the
pituitary pars intermedia (pigmentation). α-MSH, γ-lipotropin, β-endorphin and β-MSH are formed in
the brain.
Synthesis of peptide analogues: endogenous peptides are often metabolized quickly. Knowledge of
the AA sequence and characteristics of a peptide creates opportunities to develop new analogues
with increased stability, improved activity, and fewer side effects. Pharmacological activity of
analogues provides insight into the structure-activity relationship (SAR).
,Possible structural changes: shortening the chain by removing an AA (elision), lengthening the chain
by inserting an AA (intercalation), changing an AA (changing the side chain), replacing an L-amino
acid by a D-amino acid, blocking an end group, replacing S-S bridges by ethylene bridges or by Ch2
bonds.
Growth hormone
!>
Effects of growth hormones include growth in almost all body cells, in particular chondrocytes in
epiphyseal plates of long bones (longitudinal growth) and skeletal muscle. Also, GH also influence the
metabolism in protein anabolic, glucose-sparing, and lipolytic.
Regulation of growth hormone secretion:
GHRH: polypeptide (40-44 AA), activation of adenylyl cyclase (Gs). Effect enhanced by T3 (promotes
GH synthesis; synergism of metabolism and growth).
Somatostatin: polypeptide (14 AA), inhibition of adenylyl cyclase (Gi). In the pituitary gland,
suppression of GH and TSH secretion (feedback effect of T3). In the pancreas, suppression of insulin
and glucagon secretion (paracrine).
Somatomedins (‘insulin-like growth factors’, mainly IGF-1): peptide (70 AA), homology with insulin,
tyrosine kinase activity.
Growth hormone:
GRH: growth hormone-releasing hormone = somatoliberin. Peptide, 44 AA, half-life 5min, used for
diagnostics.
Somatostatin: tetradecapeptide, half-life 2 min.
GH = growth hormone = somatotropin: polypeptide (MW 22.000), half-life 20min, substitution using
gene technology. Saving hormone (increased body protein, decreased fat,
decreased glucose consumption).
IGF-1 = insulin-like growth factor-1: somatomedin C, polypeptide (MW
6.000), half-life 60 min
GH signal transduction: in dimer form > phosphorylation > JakStat signal
transduction
IGF-1 signal transduction >>
, Metabolic effects of growth hormone:
!!
Excessive production of growth hormone:
- Adolescents: gigantism (> 210 cm)
- Adults: acromegaly > deformation of bones/skull/hands/feet, growth of soft tissues and
roughening of the skin, hypophyseal diabetes (glucose intoleration)
➢ Use of somatostatin analogues
Octreotide, Lanreotide: somatostatin analogues
Synthetic peptides with a prolonged duration of action compared to
somatostatin. Applications include acromegaly preceding and, if
necessary, following hypophysectomy. Tumours like pituitary adenomas
(TSH), pancreas (insulin, glucagon), gastrointestinal tract (VIP). Bleeding
oesophageal varices like vasoconstriction, restriction of motility.
Pegvisomant: growth hormone receptor antagonist.
Growth hormone deficiency: possible causes
Dwarfism, including proportional dwarfism
- Abnormalities in the hypothalamus (GHRF) or pituitary gland (GH), including genetic
abnormalities
- GH receptor defect, reduced IGF-1 production (Pygmies, < 140 cm)
- Abnormal IGF-1 receptor
Treatment of growth hormone deficiency:
- Somatropin (recombinant hGH) > growth disorder, once
daily s.c., for several years
- Mecasermin (recombinant hIGF-1) > IGF-1 deficiency
(mutations in GH receptor, IGF-1)
- Sermorelin (GHRF analogue) > application in diagnostic of
GH secretion
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