I.

Endocrine System ES anatomy basics

A.
B.

Exocrine gland: Ducts , Lumen and surfaces

Endocrine gland :Chemical messengers
Blood stream

Paracrine Hormones Act on cells

near the secreting cell
Autocrine Hormones Act on the
secreting cell
Neurocrine Hormones Secreted by
neural cells
neurotransmitters
neurohormones

II. Hormones

They are chemical messengers

Secreted by endocrine gland

Specific to target
Activate cellular change
- 4 different chemical types:

1.
2.
3.
4.

Peptide/ Protein
Steroid
Amine
Eicosanoid

Chemical Classificaton of Hormones

1. Steroid Hormones:

Small, Lipophilic, Travel in blood w/carrier, Cytoplasmic or nuclear

receptors
change protein synthesis
Endocrine organs: Adrenal cortex, Ovaries,Testes&placenta

2.Nonsteroid Hormones:

Hydrophilic, Large, Not lipid soluble

Received by receptors external to the cell membrane

second messenger (cAMP).
Endocrine organs
Thyroid gland, Parathyroid gland, Adrenal medulla, Pituitary gland
& pancreas

They are:
1)Protein/Peptide Hormones
Example: Most hormones as Insulin,hypothalamic &
pituitary hormones
2) Amine
Synthesized from a single amino acid e.g
Melatonin from tryptophan
Thyroid hormoneT3&T4 from tyrosine
Catecholamines (EPI, DA) from tyrosine
3) Eicosanoid:
Produced from 20-carbon fatty acid, arachadonic
acid
Produced in all cells except RBCs
They have 2nd messenger as Prostaglandins and
leukotrienes in inflammation

Hormone + Receptor

The Endocrine System

STIMULUS
Hypothalamus
Releasing Hormone
(Release-Inhibiting Hormone)

Pituitary
Stimulating Hormone

Gland
Hormone

Target

homeostasis Feedback Mechanisms

Stimulus:
change in homeostatic environment
signal sent to CNS

Response
signal sent from CNS
produce effect
body returns to homeostasis

Where are Hormones Made ?

The H-P-A
Hypothalamic-Pituitary Axis
Most feedback loops run
through this axis

Hypothalamus (general) Connection to

pituitary:
Neuronal to POSTERIOR
PITUITARYneurohypophysis
Endocrine to ANTERIOR
PITUITARYadenohypophysis
RH = Pituitary releasing hormones
RIH = Pituitary release inhibiting
hormones

Why is the Hypothalamus so Important?

1. Secretes regulatory hormones

RH & RIH
2. "Directs" pituitary

Release Inhibiting Hormones

Somatostatin
Prolactin release inhibiting hormone-PIH
{Dopamine}

Releasing Hormones

Thyrotropin releasing hormone-TRH

Growth hormone releasing hormoneGHRH

a) Hypothalamic Hormones

Peptides synthesized in hypothalamus and transported to the anterior

pituitary via portal circulation
1. Gonadotropin releasing hormone{GnRH } ,gonadorelin used for induction
of ovulation, PMS,, and central precocious puberty.

2. Somatostatin GHIH, an analog, octreotide acetate (Sandostatin) used to

treat acromegaly, carcinoid, and VIP secreting tumors. Long acting form
now available (once per month).
3, Growth hormone releasing hormone GHRH, for treatment of GH
deficiency. Will only work in patients with functioning pituitary.
4. TRH
5. CRH
6. Prolactin inhibiting hormone{Dopamine}

b) Hypothalamic neurohormones
Neurosecretory Cells:
Specialized neurons

Their nuclui Synthesize and

secrete hormones

Axones extend from

HYPOTHALAMUS to POSTERIOR
PITUITARY
Secreting Antidiuretic Hormone
(ADH), Oxytocin

1. Posterior Pituitary Hormones

Manufactured in Hypothalamus, released from Post.

Pit., both are nonapeptides
Oxytocin

Target = smooth ms. Uterus and Breast (&brain)

Function = labor and delivery, milk ejection,(pair
bonding)

ADH (Vasopressin AVP)

Target = kidneys
Function = water reabsorption

I. Posterir Pituitary hormones

A.
ADH
Chemistry polypeptide chain.
Mechanism of action: 3types of receptors(V1, V2
&V3) .
Pharmacological action: 1.Renal: water
reabsorption(V2)
2.Non renal: VCBl pr.spasmogenic for SM
&platlet aggregation(V1)
Diabetes Insipedus: ADH due to disease either in
hyopothalamus or pituitary
Or nephrogenic cause
Clinical uses:

1.DI

2. oseophageal varices

3. persistant nocturnal
enuresis{Desmopressin}

Side effects:1.water retention ,bl

pr.,uterine& GIT spasm
2.Coronary spasmangina pectoris

A. Positive Feedback

Not common
Classic example:
Action of OXYTOCIN on uterine
muscle during birth:
Baby pushes on cervix
Nervous signal to Hypothalamus
Hypothal. manufactures OXY
OXY transported to POSTERIOR
PITUITARY & released
OXY stimulates uterine contraction
Loop stops when baby leaves birth canal

2. Anterior Pituitary Hormones

HORMONE

TARGET

FUNCTION

Thyroid (TSH) Stimulating

Thyroid gland

TH synthesis &
release

Growth (GH)

Many tissues

growth

AdrenocorticoTropin (ACTH)

Adrenal cortex

Cortisol release
(androgens)

Prolactin (Prl)

Breast

Milk production

Follicle (FSH)

Gonads

Egg/sperm prod.

Luteinizing (LH)

Gonads

Sex hormones

1. Growth Hormone

Stimulus = Tissue growth/ repair

Hypothalamus releases GHRH

Anterior Pituitary releases GH
Protein synthesis, growth,
etc.
GH and release of
somatostatin shuts off GHRH
and GH release

1. Growth Hormone

Physiological actions:
Mechanism GH receptor
stimulation activates an intracellular
tyrosine kinase, JAK2, resulting in
phosphorylation of proteins and gene
regulation.

3. Carbohydrate and lipid

metabolism GH appears to
promote use of lipids as energy
source instead of carbohydrates
GH has a diabetogenic effect in
diabeticsss

1.Growth almost all body tissues

stimulated to grow

4. Conserves muscle at the expense

of fat during stress

2. Nitrogen metabolism increased

nitrogen retention, amino acid
transport into tissues, and
incorporation into protein

Insulin-like growth factor (IGF,

somatomedins) peptides produced
by liver and other tissues in
response to GH; appear to mediate
many GH effects

Growth Hormone

Clinical applications :with long-term

therapeutic utility.
Recombinant human growth hormone (rhGH) is used clinically.
There are two forms, somatotropin and
somatrem.
1. Hypopituitary dwarfism in children with
insufficient GH secretion, GH will
generally produce an increased growth rate
over several years
2. Treatment of AIDS associated wasting
3. Treatment of adult onset growth hormone deficiency
4. Turners syndrome

5. .Anti-aging supplements OTC supplements

suggest they contain hGH. Contain amino acid
which that are supposed to release GH.

hypersecretion of GH

It may result in acromegaly. Treated by:

I) Octreotide (Sandostatin) or other somatostatin
analogs are most commonly used to decrease GH
secretion.
2) Dopamine agonists such as bromocryptine
will inhibit GH secretion from some GH
secreting tumors.
3.) Pegvisomant (Somavert), a GH receptor
antagonist, prevents GH stimulation of IGF.

GH as an
Adult,
Acromegly

GH as Juvenile
Giantism

2. Gonadotropins

Luteinizing hormone (LH, interstitial cell

stimulating hormone)

Follicle stimulating hormone (FSH)

Chemistry glycoprotein hormone with 2 peptide

chains
.
Physiological actions
Mechanism specific LH & FSH receptor
stimulation activates Gs
1. Ovary : LH promotes ovulation and
luteinization of ovarian follicles; stimulates
synthesis and secretion of estrogen and
progesterone from corpus luteum.
: FSH promotes follicular development

2. Testis : LH stimulates interstitial (leydig) cells

to secrete androgens, FSH stimulates testicular
growth and maintain seminiferous
tubulesSpermatogenesis

Gonadotropins

Clinical application
1. Infertility menotropins (a mixture of
urinary LH and FSH) and HCG have been used to
induce ovulation.
2. May also increase fertility in men, also LH used
in male hypogonadism
(N.B) . Hyperstimulation of ovary may occur

predict time of ovulation by measuring urinary

LH
Recombinant human LH lutropin alpha is now
available.
recombinant human FSH, follitropin & urinary
human FSH, urofollitropin promote ovulation

Gonadotropins

- Chorionic gonadotropin (HCG) not a pituitary hormone but is similar to the

pituitary gonadotropins
Chemistry glycoprotein with 2 polypeptide chains. Synthesized by of
placenta. Recombinant human HCG, choriogonadotropin alfa is used
clinically.
Physiological actions: has LH actions
Clinical application :
1. induction of ovulation, promote descent of testes in cryptorchism
2. Presence of HCG in urine used to confirm diagnosis of pregnancy
Human Menopausal GonadotropinHMG has LH&FSH actions

3. Prolactin - PRL

Chemistry Glycoprotein hormone under control of dopamine {PRIF}

Physiological actions
1. Lactation causes growth and development of breasts, and increased synthesis
of milk proteins
2. Decreases release or effectiveness of gonadotropins!?

Hypersecretion hyperprolactinemia may cause galactorrhea, amenorrhea and

infertility.
(D2 agonists)Bromocriptine, pergolide, and cabergoline are useful in
suppressing PRL secreting tumors.{PRIF}

4. Thyrotropin (TSH)

Chemistry glycoprotein with 2 polypeptide

chains.
Thyrotropin alpha, human recombinant TSH, is
used clinically.

Physiological actions Receptor stimulation

activates Gs which increases function of thyroid
gland:

Increases uptake of iodine by thyroid, synthesis and

release of hormone, and growth of gland.

Clinical application
Increases uptake of radioactive iodine. Used as a
diagnostic tool for serum thyroglobulin testing or
whole body scanning in the follow-up of patients
with thyroid cancer.

5.Corticotropin(Adrenal cortex trophic hormone, ACTH)

Chemistry single chain polypeptide of 39

amino acids.
Physiological actions stimulates adrenal
cortex to synthesize and secrete cortisol,
corticosterone, and aldosterone (slightly).
Prevents atrophy of adrenal cortex.
Mechanism receptor interaction results in
activation of adenylate cyclase and synthesis of

cAMP

Clinical use: IM or SC
Diagnosis of adrenal
insufficiencyprimary(cortex) or
secondary(Pit.)
Treatment of inflammation
.

B. Negative Feedback, Thyroid

Most common control mechanism

Level of hormone in blood or
bodys return to homeostasis,
shuts off loop at hypothalamus and
pituitary

Basic Structure of Feedback Loop

Environmental Stimulus
Stimulates Control Center (Brain-hypothal.)
Hypothalamic hormones stim. Pituitary
Pituitary hormone stim. Target area
Target area produces change
Change acts negatively or positively on the cycle.

Thyroid Problems

Goiter

Hyposecretion of TH

How Does Hypersecretion of GH

Happen?

Adrenal Gland
Adrenal gland located atop kidney
Outer part = cortex
Secretes Cortisol (stress), Androgens,
Aldosterone (electrolytes)

Inner part = medulla

SNS control
Secretes EPI & NEPI (fight or flight)

Adrenal Insufficiency

Addisons disease--hyposecretion of cortisol

JFK
Darkened skin (ACTH mimics MSH)
Weight loss, hypoglycemia
Find the anomaly in the feedback loop.
Inability to handle stress

4. Sex Steroids

Stimulus = low circulating T or E

Hypothalamus = GnRH
Anterior Pituitary = FSH & LH
Gonads produce T and E
High T and E shut off GnRH and FSH/LH

Too many steroids

2. Steroid Hormones

Derived from cholesterol

Hydrophobic/Lipophilic
Travel with a protein carrier
Long 1/2-life
Binds to cytoplasmic or nuclear receptor
1st Messenger

Steroid hormones cont.

Genomic effect
Activates genes
Directs synthesis of new proteins

Lag time between hormone binding

and effect = long time.
Gonads & placenta
Adrenal cortex

4. Eicosanoid hormones
Produced from 20carbon fatty acid,
arachadonic acid
Produced in all cells
except RBCs
2nd messenger
Prostaglandins and
leukotrienes
inflammation

Negative Feedback

Low levels of T3 or T4 in blood or low BMR = stimulus

Hypothalamus releases TRH
TRH stimulates the ANTERIOR PITUITARY to release TSH
TSH stim. Thyroid to release T3 & T4
Levels of T3 & T4 shut off Hypothal. & Anterior Pituitary

Adrenal cortex feedback

Low glucocorticoid
(cortisol) levels or low
blood sugar
Stim. Hypothal. = CRH
CRH stim. Anterior Pit. =
ACTH
ACTH stim. Adrenal
Cortex.
Increase glucocort. Level
then blood sugar level

Adrenal gland

Adrenal Problems: Cushing syndrome, hypersecretion