GENERAL CONCEPTS

OF
HORMONE
PHYSIOLOGY
Hypothalamic neurons
that secrete hormones
stimulating the
anterior pituitary to
secrete its hormones.
The cell body of hypothalamic neuroendocrine
cells is located in the hypothalamus. The axons
project to the median eminence.

The hormones they release reach the anterior

pituitary gland where they stimulate the release
of hormones.

The anterior pituitary gland is composed

of various types of hormone-secreting cells.
The Brain is Highly Vascularized
Astrocytes and the Blood-Brain Barrier
 Comparison between general and brain capillaries
Pericyte is a smooth muscle cell

Fluid-phase endocytosis: non-specific

mechanism to internalize molecules.
Receptor-mediated endocytosis: specific Non-existent
process to internalize ligands into clathrin-coated in brain
endosomes.
6
Molecular composition of the tight junctions in the BBB

Zona occludins and

accesory proteins
mediate the interactions
of the TJ with cytoskeletal
actin

M, junctional adhesion molecules; ZO, zona occcludin; AF-6, 7H6, accessory

7 pro
Hypothalamic
neurons whose
axons terminate and
comprise the posterior
pituitary gland.
The cell bodies of neurons that innervate the
posterior lobe of the pituitary gland are located in
the hypothalamus.

The axons of these neurons project past the

median eminence and enter the posterior lobe
of the pituitary where they release the hormone.

The posterior lobe is also called the neural lobe

because it contains the axon terminals that
release the hormones.
Hormones of the posterior pituitary

OXYTOCIN

ANTI-DIURETIC HORMONE
Thyroid hormones are made from the amino acid
tyrosine. The same is true for epinephrine and
norepinephrine.
 Types of Hormones

Type of compound Precursor Examples

Amines amino acids norepinephrine/epineprhrine

Peptides amino acids anti-diuretic hormone,

oxytocin,somatostatin, etc.

Protein amino acids parathyroid hormone, growth

hormone, prolactin

Glycoprotein protein and follicle-stimulating hormone,

carbohydrate leutinizing hormone, thyroid-
stimulating hormone

Steroid cholesterol estrogen, cortisol, androgen,

aldosterone
 Hypothalamic hormones

Growth hormone-releasing hormone release of GH

Growth hormone-inhibiting hormone inhibits release of GH

Gonadotropin-releasing hormone release of LH

Corticotropin-releasing hormone release of ACTH

Thyrotropin-releasing hormone release of TSH

Oxytocin uterine contractions

ejection of milk into ducts

Anti-diuretic hormone water conservation

 Anterior pituitary hormones
Growth hormone general synthesis of ILGF’s
Prolactin mammary glands milk production

Thyroid-stimulating thyroid gland thyroid hormone secretion

hormone

Adrenocorticotropic adrenal cortex secretion of cortisol

hormone

Follicle-stimulating gonads stimulate gonadal function

hormone/leutinizing and growth
hormone
Prolactin

Growth
hormone
Major Types of Secretions
1. Autocrine
2. Paracrine
3. Neurocrine
4. Neuroendocrine
5. Endocrine
6. Juxtacrine
Autocrine: release of insulin-like growth factor in
response to growth hormone.
Paracrine: regulation of oxytocin release by
dynorphin when co-released with anti-diuretic
hormone in the posterior lobe of the pituitary.
NEUROCRINE SECRETIONS
NEUROENDOCRINE SECRETION

HYPOTHALAMIC
NEURON

ENDOCRINE
GLAND
Blood vessel
 ENDOCRINE SECRETION

Endocrine cell Blood vessel Target cell

Categories of Hormones
Water-soluble hormones:
Amino acid hormones, peptides,
Polypeptides, glycoproteins

Fat-soluble hormones:
All steroid hormones and the thyroid
hormones
Peptide and Polypeptide Hormones

are Synthesized by a Mechanism

Requiring Repetitive Rounds of

Transcription, Translation, and

Post-translational Modifications
The expression of a gene requires several minutes
Transcription of genes involves a complex molecular
machinery that can be regulated by hormones
Translation and synthesis of a polypeptide takes
Time and requires complex post-translational
processing
Some proteins are targeted for membrane binding
Complex post-translational processing of
prohormones
Peptide hormone synthesis is a slow process.

More than one hormone is made from the same

polypeptide precursor.

Release and synthesis of the hormone are

coupled to ensure a stable pool of releasable
hormone.
Relationship between

binding of hormone to

receptor and biological

response
Receptor occupancy by hormone must show
saturation kinetics if it is to be physiologically
meaningful
Concept: the greater
the number of excess
receptors on the cell
surface, the lower
the concentration of
hormone needed to
sustain a maximal
Biological Response.
The concept of spare receptors: the number of
receptors in excess of those needed to achieve
maximal biological response.

What is an example of a
biological response?
Approximately 98% of leutinizing hormone (LH)
receptors on Leydig cells are spare receptors

Leutinizing
hormone Leydig cell of the testis

Testosterone
There are various mechanisms

by which hormone receptors

signal the binding of hormone

to the internal machinery.

Different motifs of the intracellular domain of
hormone receptors
The ß-adrenergic receptor activates adenylate
cyclase via Gs-coupled mechanism
s-GTP complex is the activator of adenylate cyclase
The signal
transduction
pathway
makes a very
important contri-
bution to cellular
physiology: it
amplifies the
response to the
hormone.
Epinephrine also binds to the 2-adrenergic
receptor. This receptor is coupled to the inhibitory
G protein Gi.

How does epinephrine inhibit cAMP formation

through the 2-adrenergic receptor?
The key concept is “chemical equilibrium.”

The epinephrine-2 receptor complex activates

Gi in the following way:
i-GTP + 
Then, how does Gi inhibit cAMP formation?


Epinephrine binds to the 1-adrenergic receptor
Growth hormone receptors and synthesis of
insulin-like growth factor 1
Steps leading to the synthesis of insulin-like
growth factor:
1. Binding of growth hormone
2. Binding of Janus kinase 2 (JAK2)
3. Autophosphorylation of JAK2
4. Phosphorylation of the receptor by JAK2
5. Phosphorylated growth hormone receptor now
binds at the signal transducer and activator of
transcription (STAT)
6. STATs become phosphorylated by activated
JAK2
7. STATs are transcription factors that allow
transcription of the ILGF-1 gene.
Steroid hormone
receptors are
transcription
factors in their
own right. The
steroid hormones
are transported
to the target
tissue complexed
to plasma binding
proteins. The
hormone
receptor is
intracellular.
The steroid and thyroid
hormone receptors
represent a superfamily
and share common
elements. They all have
a DNA binding domain
(DBD) and two hormone
binding domains or
regions (HBD1 and
HBD2).
The glucocorticoid receptor is associated with heat shock
proteins (HSP) that prevent it from binding to the DNA.

Binding of cortisol removes the HSPs causing dimerization

and recognition of glucocorticoid response elements on DNA
 Each steroid hormone has its
Response element unique response element on the
gene promotor.
Thyroid hormone receptor and chromatin structure
Thyroid hormones induce opening of chromatin
In the absence of thyroid hormone, the receptor associates
with the retinoid-X receptor (RXR) and co-repressors
containing deacetylase activity. Removal of acetyl groups
from histones cause the DNA to become unavailable for
transcription.

Binding of thyroid hormone to the receptor, activates

a histone acetyltransferase that restores the acetyl
groups on the histones leading to opening of the
DNA structure and transcription of genes responsive
to the hormone.
The structural state of chromatin determines the
tissue specificity of steroid hormones

liver cell ovarian cell

ovalbumin estrogen ovalbumin

gene is gene is
heterochromatic receptor euchromatic

Estradiol activates ovalbumin expression in ovarian

tissue but not in liver tissue where the gene is silent
Methods for the Assessment
of Endocrine Function

1.Radioimmunoassay
2. Radioreceptor assay
3. In vitro bioassay
4. Stimulation tests
5. Suppression tests
 Principle of the Radioimmunoassay

Ab, antibody; Ag, antigen; Ag*, labeled antigen

Molecular structure of antigen-antibody complex

hormone
Primary antibody recognizes the hormone and is
usually generated in a rabbit. Secondary antibody
is generated in a goat and binds all rabbit antibodies.

Unlabeled hormone
displaces radioactive
hormone
Radioimmunoassay for Testosterone (T)

[B] radioactive T bound in the presence of standard

[Bo] amount of T bound in the absence of unlabeled hormone

The radioimmunoassay involves displacement of radioactive
hormone by plasma non-radioactive hormone.

Without plasma With plasma

Radioactive hormone

Non-radioactive hormone
Problems with the radioimmunoassay:

Cross-reactivity with other hormones.

It gives amount of hormone, but: how much

of the hormone retains biological activity?

Solution to this problem:

Only hormone that retains biological activity
binds to its receptor. The plasma hormone displaces
the synthetic radioactive hormone from its receptor.
In vitro bioassay

Leutinizing
hormone Leydig cell of the testis

Testosterone
Reciprocity between trophic hormone levels
and target gland hormone levels
TROPHIC
Stimulation test is used when endocrine
hypofunction is suspected
Suppression test is used when endocrine
hyperfunction is suspected

Example: hypercortisolism is characterized by

excess secretion of adrenal cortisol. Patients are
given a high dose of the synthetic glucocorticoid
dexamethasone.
Failure to suppress cortisol secretion suggests
the presence of autonomous secretion of the
hormone or of ACTH.