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Endocrine Module
Overview of the Endocrine System
29 January 2010
Dr. Ruben G. Kasala
o
OUTLINE
I. Introduction
II. Five Major Hormone Classes
III. Functions of Hormones
A. Pituitary Gland
B. Adrenal Gland
C. Pancreas
D. Parathyroid Gland
IV. Hormone Receptors
V. Endocrine dysfunction


**audio = italicized
I. INTRODUCTION
ENDOCRINOLOGY – study of glands and the hormones they
produce
Started endocrinology by coining the term:
HORMONE - internal secretion of endocrine
glands
MacCallum and Voetlin
o discovered the link between the parathyroid
glands and calcium metabolism
The impart of advances in organic chemistry and
radioisotopes in endocrinology
o 1904: Stolz was able to synthesize EPINEPHRINE
o 1927: Harrington and Barger synthesized
THYROXINE
o 1930s: Joliot-Curies – discovered isotopes that
can be used for the evaluation of the thyroid
gland
** In the evolution of endocrinology, the introduction of
radioimmunoassay help pave the way in measuring the hormones
secreted by endocrine gland

Highlights of History of Endocrinology

1889 – Charles Edouard Brown-Sequard
o
professor of College de France
o
introduced the concept of chemical
messengers - secreted into the blood exert
systemic effects
o Experiment: Self-administration of extracts of
animal testes, he discovered that he got
stronger and improved intellectual and sexual
potency

1891 –George Murray
o English Physician
o achieved the first success in treating myxedema
(hypothyroidism)
o Experiment: gave the patient an extract of the
thyroid gland

1894 – Sharpey-Schafer and George Oliver
o demonstrated that in the extracts of adrenal
glands, there is a substance that raises the
blood pressure: EPINEPHRINE and NOREPINEPHRINE (catecholamines)

1905 – Ernest H. Sterling
o
brilliant pupil of Sharper-Schafer
Group 6
1956 – Rosalyn Yalow, Solomon Berson observed
antibodies to insulin that led to development of
radioimmunoassay for measuring insulin level
o Within a short period, sensitive RIA of high
specificity were developed for many peptide,
thyroid, and steroid hormones
ENDOCRINE vs. EXOCRINE

Endocrine: hormones secreted internally then goes into
the circulation

Exocrine: hormones secreted externally into a lumen
such as in the GIT
o
that’s why hormones secreted by the pancreas
goes into the GIT for absorption or for
processing food taken
Hormone – Greek phrase meaning “to set in motion”,
when it is secreted, it sets into motion a lot of
physiological activities in the body
II. FIVE MAJOR HORMONE CLASSES
1. Amino Acid derivatives – dopamine, catecholamine,
thyroid hormone (TH)
2. Small neuropeptides – secreted by the pituitary Gonadotropin Releasing Hormone (GnRH) , Thyroid
Releasing Hormone (TRH), somatostatin, vasopressin
3. Large proteins – insulin, Leuteinizing Hormone (LH),
Parathyroid Hormone (PTH)
4. Steroid hormones – from the adrenal glands and gonads
cortisol and estrogen that are synthesized form
cholesterol precursors
5. Vitamin derivatives - retinoids, Vitamin D, protein growth
factors
III. FUNCTIONS OF HORMONES
Three general areas:
1. Growth and differentiation – Insulin Growth Factor 1
(IGF-I), TH, sex hormones: testosterone and estrogen
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BATCH 2014  Overview of the The Endocrine System
2.
3.
Maintenance of homeostasis
– TH: controls 85% of the basal metabolism in most
tissues
- Cortisol: exerts a permissive action for many hormones
in addition to its direct effects
- PTH: important for homeostasis of Calcium and
phosphorus
- Vasopressin (Antidiuretic hormone): secreted by the
posterior pituitary, regulates the osmolality and water
balance
- Mineralocorticoids: regulates vascular volume and
electrolytes
- Insulin: regulates blood sugar
Reproduction – LH, GnRH, inhibin, Epidermal Growth
Factor and vascular epithelial growth factor, prolactin,
oxytocin
2.
Oxytocin – important for stimulation of smooth muscles
of the uterus and milk ejection/let-down
*interrelationship that interconnects the master endocrine organ:
pituitary and other endocrine organs

1909 Tandler and Grosz described pituitary enlargement
after castration of men

Carl R. Moore and Dorothy Price:
o First experimental evidence for feedback
control of gonadotrophins - showing a
reciprocal relationship between the testes and
the anterior pituitary
o Subsequently, similar reciprocal relationship
between ovaries and pituitary gland
A.PITUITARY GLAND
1. Anterior Pituitary – secretes most of the hormones which
stimulate the adrenal gland. (TSH, ACTH, FSH, GH, PRL, Endorphins)
1. thyrothropin-releasing hormone stimulates the thyroid
gland to produce TH
2. prolactin is under the control of dopamine of the ant.
pituitary; for the mammary gland
3. adrenocorticotropin hormone stimulates adrenal gland
4. growth hormone – for the adipose tissue, bone and
muscles
5. follicle stimulating hormone and leutenizing hormone –
for the testes and ovaries
6. melanocyte stimulating hormone
“corticotrophic” – coming from pituitary gland
“trophic” – stimulates
Adrenocorticotrophic = coming from the pituitary to simulate the
adrenal gland
Gonadotrophic (FSH and LSH) – from the pituitary to stimulate the
gonads
2. Posterior Pituitary
1. Antidiuretic hormone (ADH) – protects the kidney and
maintains water balance and volume
Group 6
** negative feedback - important in the evaluation of the hyper/
hypofunction of endocrine glands
- releasing hormones from the hypothalamus which
stimulate the pituitary gland to release trophic hormones
which then stimulate endocrine organs to produce the
endocrine hormones
-endocrine hormones send a negative signal to the
pituitary and hypothalamic area to maintain normal levels of
hormones
if there is no negative feedback, continuous stimulation of
endocrine organs will lead to hypersecretion of endocrine
hormones that will have adverse effects
** Dopamine is a derivative of the amino acid tyrosine. Its principal
function in the hypothalamus is to inhibit the release
of prolactin (PRL) from the anterior lobe of the pituitary.
Clinical Application:
If a tumor blocks the pituitary stalk, adrenal hormones (cortisol) will
be low, thyroid hormones will be low BUT prolactin will have high
levels because there will be no inhibitory effect.
Why do you think the blood sugar of a patient is elevated when
given steroids?
-due to stimulation of gluconeogenesis, protein
metabolim and glycolysis (in the adipose tissue)
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BATCH 2014  Overview of the The Endocrine System
B.
ADRENAL GLAND
Adrenal Cortex

Zona Glomerulosa – aldosterone

Zona Fasciculata – cortisol

Zona Reticularis – androgens
**GFR is ACA or ACT(testosterone, an androgen)
Adrenal Medulla – Epinephrine and Nor-epinephrine
**glucose is transported by GLUT2
Glycolyisis produces ATP (36), ATP stimulates potassium sensitive
channels, where diabetes medication attaches
OBESITY
Too much adipose tissue secretes leptin.
RENIN – ANGIOTENSIN ALDOSTERONE SYSTEM
** Aldosterone - helps in the maintenance of volume and electrolyte
levels.
1. When volume is low, it stimulates the juxta-glomerular
apparatus (JGA) to release renin.
2. Renin then converts angiotensin I from angiotensinogen
3. Angiotensin I is then converted to angiotensin II
4. Angiotensin II stimulates aldosterone.
** Aldosterone stimulates potassium, renal excretion, and renal
sodium retention which maintain the volume.
** when you are dehydrated you stimulate RAA system and ADH
release = water retention
C. Pancreas
**In obesity, there is leptin resistance.
**Adipose tissue  leptin  neg feedback hypothalamus 
decreased Neuropeptide Y  decreased hunger, increased activity,
increased thermogenesis, increased sympathetic activity
Central Effect of Leptin
** Diabetes and abnormalities in glucose-simulated insulin
secretion.
(Glucose and other nutrients regulate insulin secretion by
pancreatic beta cell. Glucose is transported by GLUT2 glucose
transporter; subsequent glucose metabolism by the beta cell alters
ion channel activity leading to insulin secretion.)
Group 6
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BATCH 2014  Overview of the The Endocrine System
D.
PARATHYROID GLAND

Found in the posterior aspect of the thyroid
gland (usually 4)

Secretes PARATHYROID HORMONE
o maintains calcium metabolism

by calcium resorption from
the bone

or stimulating the kidney
1,25-Dihydroxyvitamin D
_____________________________________________________
2.
Intracellular nuclear receptors – lipid soluble steroids,
TH, vit D and retinoids
Example: Thyroid Hormone receptors
Hormone receptors CROSS-TALK (cross reactions)
**Hormone A specifically attaches to Hormone A receptor and
produces a specific signal,
but sometimes Hormone B attaches to Hormone A receptor and
produces the same effect as Hormone A.
1.
IV. HORMONE RECEPTORS
** Endocrine hormones exert their effects on hormone receptors
**endocrine hormones always attach to SPECIFIC receptors
2.
1.
Cell-surface membrane receptors – amino acid
derivatives and peptide hormones
Example: INSULIN SIGNAL TRANSDUCTION in SKELETAL MUSCLE
3.
4.
** The insulin receptor has intrinsic tyrosine kinase activity and
interacts with insulin receptor substrates
** insulin exerts its effect through the membrane receptor,
Eventual outcome = stimulation of GLUT 4, transporter of glucose.
This opens up the plasma membrane for absorption of glucose for
glycolysis and ATP production.
Human Chorionic Gonadotropin(HCG) and Thyroid
Stimulating Hormone(TSH) - when there is a lot of HCG,
it can stimulate TSH receptors and cause hyperthyroidism
Parathyroid Hormone related peptide (PTHrp) and PTH –
as in certain tumors, they produce PTHrp, which can
stimulate PTH receptors = patient develops hypercalcemia
Insulin Growth Factor II (IGF-II) precursor and insulin
and IGF 1 receptor
ACTH and MSH
** NELSON SYNDROME
If you remove both adrenal glands, ACTH levels
would rapidly increase, ACTH stimulates
melanocyte stimulating hormone = patient gets
darker
Hormones are also bound to Serum-binding proteins in the
circulation
1. Thyroxine (T4) and triiodothyronine (T3): Thyroxine Binding
Globulin and Albumin and Thyroxine Binding PreAlbumin
(TBPA)
2. Cortisol: Cortisol Binding Globulin (CBG)
3. Androgen and estrogen: Sex Hormone Binding Globulin(SHBG)
or Testosterone binding globulin (TeBG)
4. IGF-I and II : IGF-binding proteins (IGFBPs)
5. GH : GH-binding protein (GHBP)
V. ENDOCRINE DYSFUNCTION
Causes of endocrine dysfunction
Type of
Endocrine
Disorder
HYPERFUNCTION
Neoplastic
Benign
Malignant
Ectopic
Autoimmune
Group 6
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Examples
Can be iatrogenic (cushing’s syndrome), thyrotoxicosis
Tumor in the pituitary gland
*Pituitary adenomas,
*hyperparathyroidism, *autonomoius thyroid or
adrenal nodules – nodule will secrete excess thyroid
hormone = hyperthyroidism, *pheochromocytoma –
tumor in the adrenal gland = excessive secretion of
epinephrine = patient is hypertensive (tumors that
secrete specific endocrine hormones)
*Adrenal cancer, *medullary thyroid cancer,
*carcinoid
*Ectopic ACTH (lung carcinoma) = increased ACTH =
Cushing’s syndrome,
*SIADH Secretion
*Antibody cross talks with the endocrine hormone
receptor: Grave’s disease – secretes a TSH receptor
antibody = stimulates excess TH = Hyperthyroidism
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BATCH 2014  Overview of the The Endocrine System
HYPOFUNCTION
Autoimmune
Iatrogenic
Infectious/inflammatory
Hormone mutations
Enzyme defects
Developmental defects
Nutritional/vitamin
deficiency
Hemorrhage/infarction
Hormone Resistance
Receptor Mutations
Membrane
Nuclear
Signalling pathway
mutations
Postreceptor
Hashimoto’s thyroiditis, type I diabetes mellitus,
Addison’s disease, polyglandular tissue
Radiation-induced hypopituitarism,
hypothyroidism, surgical, radioactive iodine
Adrenal insufficiency, hypothalamic sarcoidosis
GH
Iodine deficiency = hypothyroidism
Hemorrhage in the pituitary = shehan’s
syndrome
GH, vasopressin, LH, FSH, ACTH,
ENDOCRINE DISEASES
1. Hyperthyroidism
o Gigantism
o Acromegaly
o Exopthalmos in Graves’ disease – TSH receptor
antibodies exert its effect = excess TH production =
negative feedback on pituitary = increase ACTH
o Subacute Thyroiditis
o Toxic Adenoma
2. Hypothyroidism
o Cretinism – from infancy
o Multinodular Goiter – thyroid is normal but
abnormality in the anatomy (can also be
autonomous and cause hyperthyroidism)
o Thyroid Cold Nodule – nodule that is not functioning
o Hypervascular Thyroid Nodule – detected through
ultrasound
o Metastatic thyroid carcinoma
3. CUSHING’S SYNDROME – tumor in adrenal gland
o Hypersecretion of ACTH by the pituitary gland
o Protein depletion
o Thin skin with abnormal reddish striae
o Weak muscles
o Poor wound healing
o osteoporosis
o Hyperglycemia
o Body fat redistribution (not symmetrical)
o Moon facies
o Hirsutism
o CNS, symptoms
o Water retention  increased BP
4. ADDISON’S DISEASE – opposite of Cushing’s
5. ANDROGENITAL SYNDROME
6. SECONDARY HYPERTENSION due to endocrine problem
o Pheochromocytoma
o Primary hyperaldosteronism – tumor of the adrenal
cortex
o Congenital adrenal hyperplasia
7. Chromosomal abnormalities
o Klinefelter’s syndrome
o Turner’s Syndrome
Group 6
Common Endorcine disorders and screening tests
Disorder
Approximate
Screening/testing
prevalence in
recommendations
adults
Hyperlipidemia
20-25%
Cholesterol
screening at least
every 5 years
More forten in highrisk groups
Hypothyroidism
TSH screening test
*when hypothyroidism
is not severe(subclinical
hypothyroidism) T3 and
T4 can be normal
Graves’ disease
Thyroid nodules and
neoplasia
Osteoporosis
Hyperparathyroidism
TSH and T3 and T4
Ultrasound, physical
examination, Fine
needle aspiration
Bone mineral density
screen with TSH,
Serum Calcium, and
random Cortisol
Infertility
Polycystic ovarian
syndrome
Hirsutism
Menopause
Klinefelter syndrome
Turner syndrome
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RESEARCH: (this was discussed in class in passing)
MEN stands for "Multiple Endocrine Neoplasia".
The MEN syndromes are conditions which cause overactivity
and enlargement in certain endocrine glands. MEN syndromes
are usually (but not always) inherited conditions and therefore
they run in families. When they are inherited, they are passed
from one generation to the next.
THREE MAIN TYPES OF MEN
Each type of MEN is associated with a specific cluster of
illnesses. The main health problems in each of the MEN
syndromes are:

MEN 1 = Parathyroid tumors, pancreatic tumors,
and pituitary tumors.

MEN 2a = Medullary thyroid
cancers (MTC), pheochromocytoma,
and parathyroid tumors.

MEN 2b = Medullary thyroid
cancers, pheochromocytoma and neuromas.
There are specific genetic causes for each of the three types of
MEN. Any particular MEN family will have only one type of
MEN, either MEN 1, MEN 2a or MEN 2b. Therefore, families
with one type of MEN do not have an increased risk of
developing an other type of MEN.
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