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Hormones 1 13
Hormones 1 13
n
HORMONES CAN AFFECT ANY
OF THE FOLLOWING STEPS:
n Hormones can be thought of as signals,
and receptors are signal detectors
n Each component serves as a link in the
communication process between
extracellular events and chemical
changes within the cell
General Features of Hormone
Classes
Group I Group II
Types Steroids, Polypeptides, proteins, glycoproteins,
Solubility Lipophilic
iodothyronines, Hydrophilic
catecholamines
Transport Yes No
Plasma calcitriol, retinoids
proteins half-life Long (hours to days) Short (minutes)
Receptor Intracellular Plasma membrane
Mediator Receptor-hormone cAMP, cGMP, Ca2+ , metabolites of
complex complex phosphoinositols, kinase
cascades
Classification of Hormones by
Mechanism of Action
I. Hormones that bind to intracellular receptors
Androgens
Calcitriol (1,25[OH]2-D3)
Estrogens
Glucocorticoids
Mineralocorticoids
Progestins
Retinoic acid
Thyroid hormones (T3 and T4)
Classification of Hormones by
Mechanism of Action
II. Hormones that bind to cell surface receptors
A. The second messenger is cAMP
Protein kinase C
requires calcium
for maximum
activity
Tyrosine (Y)
JAK-STAT signaling pathway
n Takes part in the regulation of cellular
responses to cytokines and growth
factors
n Cytokines are a group of proteinaceous
signalling compounds that, like
hormones and neurotransmitters, are
used extensively for inter-cell
communication.
JAK-STAT signaling pathway
n Employing Janus kinases (JAKs) and
Signal Transducers and Activators of
Transcription (STATs), the pathway
transduces the signal carried by
extracellular polypeptides to the cell
nucleus, where activated STAT proteins
modify gene expression
n JAKs, which have tyrosine kinase activity, bind to some
cell surface cytokine receptors
n The binding of the ligand to the receptor triggers
activation of JAKs. Jak-P, an active kinase,
phosphorylates the receptor on tyrosine residues
n The STAT proteins associate with the phosphorylated
receptor and then are themselves phosphorylated by
Jak-P
n STAT dimerizes, translocates to the nucleus, binds to
specific DNA elements, and regulates transcription
n The transcription factor NF- κ B (Nuclear Factor
kappa B) is a heterodimeric complex typically
composed of two subunits termed p50 and
p65
n Normally, NF- κ B is kept sequestered in the
cytoplasm in a transcriptionally inactive form
by members of the inhibitor of NF- κ B (Iκ B)
family
n Extracellular stimuli such as proinflammatory
cytokines, reactive oxygen species, and
mitogens lead to activation of the Iκ B kinase
complex, IKK, which is a heterohexameric
structure consisting of α , β , and γ
subunits.
n IKK phosphorylates Iκ B on two serine
residues, and this targets Iκ B for
ubiquitination and subsequent
degradation by the proteasome
n Following Iκ B degradation, free NF- κ B can
now translocate to the nucleus, where it binds
to a number of gene promoters and activates
transcription, particularly of genes involved in
the inflammatory response
n Glucocorticoid hormones are
therapeutically useful agents for the
treatment of a variety of inflammatory
and immune diseases
n Their anti-inflammatory and
immunomodulatory actions are
explained in part by the inhibition of NF-
κ B and its subsequent actions.
Evidence for three mechanisms for the inhibition
Glucocorticoids GRE
Progestins PRE
Mineralocorticoids MRE
Androgens ARE
Estrogens ERE
Pituitary Gland
HYPOTHALAMIC HORMONES
n Controls the release of pituitary
hormones
n Hypothalamic hormones are released
from the hypothalamic nerve fiber
endings around the capillaries of the
hypothalamic-hypophysial system in
the pituitary stalk
n Released in a pulsatile manner
PITUITARY
HORMONES
GROWTH HORMONE (GH)
n Also called somatropin or
somatotropin
n Synthesized in somatotropes, a
subclass of the pituitary acidophilic
cells
n The genes for human growth hormone
are localized in the q22-24 region of
chromosome 17
n
Disulfide bonds
GROWTH HORMONE (GH)
n Peptides released by neurosecretory
nuclei of the hypothalamus into the
portal venous blood surrounding the
pituitary are the major controllers of GH
secretion by the somatotropes.
GROWTH HORMONE (GH)
n Growth hormone releasing hormone
(GHRH) from the arcuate nucleus of the
hypothalamus and ghrelin* promote GH
secretion, and somatostatin from the
periventricular nucleus inhibits it.
Secretes GHRH
n Ghrelin is a hormone produced by P/D1 cells
lining the fundus of the human stomach that
stimulate appetite
n Ghrelin levels increase before meals and
decrease after meals
n It is considered the counterpart of the hormone
leptin, produced by adipose tissue, which
induces satiation when present at higher
levels.
n Much of the growth hormone in the
circulation is bound to a protein (growth
hormone binding protein, GHBP) which
is derived from the growth hormone
receptor
n Growth hormone receptor is a member of
the cytokine receptor superfamily.
n One growth hormone molecule binds to
one receptor and then recruits a second
receptor to form a dimer through which
signalling occurs.
n The effects of growth hormone on the
tissues of the body can generally be
described as anabolic
n
n Height growth in childhood is the best known
effect of GH action, and appears to be
stimulated by at least two mechanisms: