Hormons of endocrain in body of humen pat

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‫هزاع‬ ‫فوظ‬
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Hormones
Dr/Mahfouth Ahmed Hazz'a

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Chapter 1
Endocrinology & Related Diseases
Subject Curriculum:
Endocrinology:
 Introduction.
 Hormones description and classification:
-Hypothalamus hormones (TRH, CTRH, GRH, GIF, PRH, PIF, and GnTRH)
-Pituitary hormones (Anterior loop= GH, TSH, FSH, LH and prolactin &
Posterior loop= ADH, and Oxytocin).
- Thyroid hormones ( T3 and T4).
- Adrenal hormones ( corticosteroids and aldosterone).
- Sex hormones ( Male (testosterone) and female (progesterone and
estradiol) ).
-Pineal Gland & Pancreatic Islet & Parathyroid gland

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Endocrinology
Introduction
Gland:
It is an organ in animal body that synthesize a substance such as
Hormones, breast milk,….. etc
Type of gland:
 Exocrine gland: are a gland that secret their products through a
duct e.g. sweat gland, pancreas, stomach, liver,…..etc.
 Endocrine gland ( Ductless gland): are gland that secret their
products directly into a blood stream e.g. Thyroid gland, pituitary
gland, adrenal gland,……etc.
Endocrinology:
It is the branch of biology and medicine that dealing with the endocrine
system, its diseases and specific secretion called hormones.
Hormones:
 Chemical substance acts as messenger.
 It is a chemical signal secreted into blood stream and act on
distant tissue.

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Classification of hormones:
A) According to chemical structures: Hormone classified into:
1. Protein (> 50 amino acids) or peptide ( 10 – 50 amino acids)
derivatives: e.g. Insulin ( 51 a. as), Glucagon ( 29 a. as).
2. Amino acid derivatives: e.g. Thyroid hormones ( T3 & T4) , Epinephrine
and Nor- epinephrine ( Adrenalin & Nor-adrenaline) All derived from
Tyrosine.
3. Fatty acid derivatives: e.g. Ecosanoides derived from Arachidonic acid.
Ecosanoides as:
 Prostaglandins ( Smooth muscles contraction and relaxation of
uterus).
 Thromboxines (Platelets aggregations ).
 Leukotrines ( Ag – Ab reaction).
4. Cholesterol derivatives:
e.g. Sex hormones ( Progesterone, estrogen, testosterones).
B) According to solubility and mechanism of action: Hormone classified
into:
1. Hydrophilic ( Extracellular mechanism of action): it binds with its
receptors molecules (H-R complex) on the outer surface of cell
membranes e.g. Insulin, glucagon, epinephrine.
2. Lipophilic ( intracellular mechanism of action): H-R complex either in
cytoplasm or in nucleus e.g. Thyroid hormonesT3, T4 ( In cytoplasm), Sex
hormones (In nucleus).

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Hormone action:
Figure 1. Signaling via G protein-coupled receptors. Ligand binding to its
cellsurfacereceptor initiates interaction of the receptor with the
heterotrimeric Gprotein for which it is specific. A conformational change
in the G protein broughtabout by binding of the ligand-receptor complex
promotes exchange of GDP forGTP. The activated Gα-GTP dissociates
from the Gβγ complex and both can interact with effectors, which carry
on the signal to the mechanism that implements the cellular response.

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Figure 2. Regulation of cyclic AMP-dependent protein kinase A (PKA) by
cyclic AMP. Activation of adenylate cyclase by binding of GαS-GTP
amplifies the signal by synthesis of many molecules of cyclic AMP. Cyclic
AMP binding to PKA causes dissociation of the regulatory subunits from
the catalytic subunits, which carry on the signal. Phosphodiesterase
regulates the concentration of cyclic AMP by catalyzing its hydrolysis to
AMP, which shuts off the signal.

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Figure 3. Signaling through protein kinase C (PKC). Activated
phospholipase C cleaves the inositol phospholipid PIP2 to form both
soluble (IP3) and membraneassociated (DAG) second messengers. DAG
recruits PKC to the membrane, where binding of calcium ions to PKC
fully activates it. To accomplish this, IP3 promotes a transient increase of
intracellular Ca2+ concentration by binding to a receptor on the
endoplasmic reticulum, which opens a channel allowing release of
stored calcium ions. PIP2, phosphatidylinositol 4,5-bisphosphate; DAG,
diacylglycerol; PLC, phospholipase C; IP3, inositol trisphosphate.

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Figure 4. Receptor tyrosine kinase signaling mediated by the Ras-MEK
ERK pathway. Binding of a growth factor (ligand) to its cell-surface
receptor promotes dimerization of the receptor with subsequent
autophosphorylation mediated by activation of the intrinsic tyrosine
kinase of the receptor’s cytoplasmic domain. Docking of the adaptor
GRB2-SOS complex promotes activation of Ras by GDP-GTP exchange.
Ras recruits the first serine/threonine kinase of the signaling pathway,
Raf. Raf then phosphorylates itself as well as the downstream kinase
(MEK), which in turn phosphorylates ERK (also called MAP kinase).
Activated ERK is capable of distributing the signal by phosphorylation of
multiple substrates leading to the cell’s pleiotropic response to the
growth factor. Reactions of the kinase cascade are denoted by the
numbers in diamonds.

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Hypothalamus and pituitary relationship:
Hypothalamus: it is a region of the brain that located at the base of
brain related to the optic tract.
Hypothalamus control the production and secretion of pituitary
hormones especially the anterior lobe.
Hypothalamic releasing factors (Hormones):
It is substances (hormones) either releasing (stimulating) or inhibiting
factors.
The function of these substances is secretion of pituitary hormones
which control the secretion of other endocrine glands.

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Hypothalamus releasing factors
Releasing hormones Function
Thyrotropin releasing hormones
( TRH)
Activate TSH
(Thyroid stimulating hormone).
Gonadotropin releasing hormones
( GnRH)
Acts on FSH (Follicle stimulating
hormone) & LH (Luteinizing hormone ).
Corticotropin releasing hormones
(CRHs)
Activate ACTH
(Adrenocorticotropic hormone).
Somatocrinin or Growth hormone
releasing hormone GHRH or GRH Activate GH ( Growth hormone)
Somatostatin or growth hormone
inhibiting factor Inhibit GH ( Growth hormone)
Prolactin inhibiting factor PIF Inhibit Prolactin.
Prolactin releasing factor PRF Activate Prolactin.

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Pituitary Hormones
Pituitary (Hypophysis) gland: it is a pea sized gland located on the base
of skull between the optic nerves
It is about 1cm long, 1.5 cm wide and 0,5 in weight.
Pituitary gland divided into three regions (lobes) :
1. Anterior lobe (called Adenohypophysis): the largest and the most
essential part.
2. Posterior lobe (Neurohypophysis or neural part).
3. Intermediate lobe: which separate the Adenohypophysis from the
Neurohypophysis.

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Pituitary hormones:
1) The Anterior lobe:
The anterior lobe contain six type of secretary cells, all which are
specialized to secrete only one of the anterior lobe hormones.
All these cells secrete their hormones response to hormones reaching
them from the hypothalamus.
Anterior lobe hormones include:
1. Growth hormone (GH) Human G.H also called Somatotropin.
2. Thyroid stimulating hormone (TSH).
3. Follicle stimulating hormones (FSH).
4. Luteinizing hormones (LH).
5. Prolactin.
6. Adrenocorticotropic hormones ( ACTH).
2) The posterior lobe:
It secrete two hormones both of them synthesized in the hypothalamus
and stored in the posterior lobe.
These hormone are:
1. Oxytocine.
2. ADH=Anti-diuretic hormone (Vasopressin).

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1-Human Growth hormone GH
Also called somatotropin.
It is a protein composed of 191 a.as.
Target organ: All tissue.
Growth hormones is anabolic hormones.
Function of hormone:
Abnormalities
 In children:
Hyposecretion of GH lead to Dwarfism.
Hypersecretion of GH lead to Gigantism.
 In adult:
Hypersecretion of GH or GHRH lead to Accromegaly.

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2-Thyroid stimulating hormone (TSH)
It is glycoprotein hormones.
Target organs : Thyroid gland.
Stimulate the thyroid gland to secrete T3, and T4.
Abnormalities:
 Defect in TSH production (increase or decrease production) lead
to over or under secretion of thyroid hormones ( T3, T4)
respectively.
___________________________________________________________
3-Gonadotropin hormones (FSH & LH):
-Gonadotropin hormones include Follicle Stimulating Hormones (FSH)
and luteinizing hormones (LH).
-FSH & LH are glycoprotein hormones.
Target organ :
 Interstitial cells of Leydig testes.
 Follicle of ovaries.
Function of hormones:
FSH:
 Ovary: Follicle development, ovulation, & estrogen synthesis.
 Testes: Spermatogenesis.
LH:
 Ovary : Luteinization, progesterone synthesis.
 Testis: Interstitial cells development, testosterone (Androgen)
synthesis.

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When FSH and LH tests done?
 Infertility.
 In female with irregular menstrual cycle ( Amenorrhea).
 When a boy or girl does not enter puberty at an appropriate time.
Abnormalities:
 In women:
Abnormal result helps to differentiate between;
- Primary ovarian failure ( Problem in ovaries themselves) ( increasing of
FSH & LH), and
-Secondary ovarian failure ( Disorder in pituitary and hypothalamus) (
Decreasing of FSH & LH).
 In men:
-Increase FSH and LH indicate primary testicular failure (Problem in
testes themselves).
-Decrease FSH and LH indicate secondary testicular failure (pituitary and
hypothalamus disorders).

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4-Prolactin PRL
Also known as luteotrphic (Luteotrophin) hormones (LTH).
It is secreted by anterior pituitary and other cells as breast, leukocytes
and prostate.
Target organs:
Mammary gland.
Effect and Function:
 In women:
 Stimulate development of the ducts in mammary gland.
 Stimulate the mammary gland to produce milk (Lactation).
 Inhibition of ovulation (During lactation).
 In men:
 Inhibit production of testosterone.
 Other function:
o Stimulation the formation of myelin.
o Play role in immune system.
 Prolactin affect menstrual cycle by the following :
-Prolactin inhibits two hormones necessary for ovulation , this hormones
are FSH and GnRH.
-When a prolactin is high (Hyperprolactiemia) the ovulation not occur
lead to infertility and also cause irregular menstrual cycle.

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Measurement of prolactin:
Prolactin released at various times throughout the day and night, it is
level affect by many factors. It increased (False result ) by:
1) Emotional and physical stress.
2) High protein meals.
3) Intense breast stimulation.
4) Recent breast exam.
5) Recent exercise.
6) Certain medications as Antidepressants, Estrogen, H2-blocker.
Normal range:
Male 2 – 18 ng/ml.
Non pregnant female: 2 – 29 ng/ml.
Pregnant female: 10 – 209 ng/ml.
Why the test is performed?
 Breast milk production without child birth.
 Impotence.
 Infertility.
 Irregular menstrual period (Amenorrhea).
Abnormalities:
i. Hyperprolactinemia ( Increase level of prolactin in the blood more
than normal rage). This is due to chest wall trauma or irritation.
ii. Hypoprolactinemia ( decrease level of prolactin in the blood less
than normal rage). This is due to pituitary tumor (Prolactinoma).

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5-Thyroid Hormones
Thyroid gland: It is a gland that found in the lower part of the neck
below ( Adam's apple).
It is like butterfly.
It's weight about 15 – 25 g.
Thyroid gland secrete two hormones T3 (Triiodothyronine) and T4
(Thyroxin).
Target cell :
All cell in the body.

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Synthesis and control of secretion of Thyroid hormones:
T3 & T4 are amino acid hormones synthesized from Tyrosine.
-About 0.03 of T3 &T4 are found as active (Free) form FT3 & FT4, The rest
(Total) are bound with prealbumin and globulin.
-Thyroid hormone secreted under control of TSH which comes from
anterior lobe of pituitary gland.

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a) In metabolism:
Thyroid hormones stimulate metabolic activities ( Increase basal
metabolic rate BMR), this lead to:
i. Increase heat.
ii. Increase O2 consumption.
iii. Increase ATP hydrolysis.
 In lipids : Increase oxidation of fatty acid in many tissue.
↑ Thyroid hormone lead to ↓ Cholesterol and Triglycerides ( this used
as an indicator for Hyperthyroidism).
 In Carbohydrate: Thyroid hormones stimulate all carbohydrate
metabolism.
b) In Growth:
Thyroid hormone play important role in growth process.
c) In Development:
Normal level of Thyroid hormone are essential for development of fetal
and neonatal brain.
d) Thyroid hormone also play important role in:
i. Cardiovascular system (Increase Heart rate and help blood to
reach to all the body).
ii. CNS (↓ Thyroid hormones lead to problem in nervous system).
iii. Reproductive system ( ↓ Thyroid hormones lead to infertility).

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Abnormalities:
A. Hypothyroidism: Deficiency in T3 ,T4 or both.
Causes:
- Decrease of iodine.
- Primary thyroid diseases.
Symptoms:
- Fatigue.
- Cold intolerance.
- Weakness.
- Reproductive failure.
- Goiter.
-Diabetes mellitus.
-Weight gain.
-Hyperlipidemia (↑LDL-cholesterol)
B. Hyperthyroidism (Thyrotoxicosis): Increase T3 ,T4 or both.
Causes : e.g. Graves diseases
Symptoms:
- Increase heart rat.
- Nervousness.
- Insomnia.
-Heat intolerance
-Weight loss
-Increase physical activity
-Ophthalmopatheis

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6-Adrenal hormones
Adrenal gland:
Also called suprarenal gland, It is a gland that located on the tope the
kidney.
It is about 7-10 gm in weight.
Adrenal gland composed of two part:
1. Cortex.
2. Medulla.
Adrenal cortex hormones:
It produce a number of corticosteroids hormones, these include:
i. Mineralocorticoides: as aldosterone.
ii. Glucocorticoides: as cortisol, cortisone, corticosterone …..etc.
Adrenal cortex produces a group of steroid hormones ( arise from
steroid nucleus).

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Adrenal medulla hormones:
It produce:
i. Adrenalin (Epinephrine).
ii. Nor-adrenalin (Nor-Epinephrine).

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A-Aldosterone
It is a steroid hormone produced by adrenal cortex.
1. Helps maintain blood pressure.
2. Helps maintain water and salt in the body ( By helping kidney to
retain sodium and excrete potassium).
Secretion control of Aldosterone:
Aldosterone secretion controlled by stimulation by several factors.
The most important one is Renin – Angiotensin system ( RAS):

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Abnormalities:
 Hyperaldosteronism: increase level of Aldosterone lead to:
 Arterial hypertension.
 Hypokalemia ( ↓ K+ level ).
 Hypoaldosteronism: Decrease level of Aldosterone lead to
 Dehydration.
 ↓ Blood pressure.
 Hyponatremia (↓ Na+).

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B-Glucocorticoids
It is a group of steroid hormones secreted by adrenal cortex.
Glucocorticoids includes : Cortisol, Cortisone, Corticosterone.
The most important one is Cortisol.
Control of secretion:
Glucocorticoids are produced in response to stimulation of ACTH that
comes from Anterior lobe of pituitary.
Function of Glucocorticoids:
Its function classified into:
1) Immunological Function:
Regulate the formation of anti-inflammatory protein ( Stop inflammation
process).
2) Metabolic Function:
1. Stimulates Gluconeogenesis ( in liver).
2. Mobilization of amino acid from extrahepatic tissue to liver.
3. Inhibits glucose uptake in muscles and adipose tissue.
4. Stimulate of fat breakdown in adipose tissue.
Function of Cortisol:
1. It helps respond to stress ( Main function).
2. It helps maintain blood pressure, heart function, and blood vessel
function.
3. It helps slow the immune system's inflammation response.
4. It helps balance the effects of insulin.
5. It helps control the metabolism of proteins, carbohydrates, and
fats.

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Abnormalities:
A. Hypercortisolism:
Causes:
i. Primary hypercortisolism ( Cushing's Syndrome)
ii. Secondary hypercortisolism ( Pituitary tumor).
Symptoms:
1. Weight gain.
2. Backache.
3. Headache.
4. Thirst.
5. Mental changes.
6. ↑ Urination.
7. Acne & Superficial skin infection.
8. Impotence and cessation of mens.
B. Hypocortisolism:
Causes:
i. Primary hypocortisolism ( Addison's diseases, Nelson's syndrome).
ii. Secondary hypocortisolism ( Pituitary tumor).
Symptoms:
1. Low blood pressure.
2. Nausea vomiting.
3. Skin changes.
4. Loss of appetite and weight loss.
5. Low blood glucose level.
6. Irregular or absent of menstrual period in women.

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7-Sex hormones
-Are steroid hormones that regulate reproductive system.
-They also play a prominent role in the biology and physiology of several
organs/tissues and in the pathophysiology of several diseases.
Types:
Sex steroids include:
A. Androgens:
1) Anabolic steroids.
2) Androstenedione.
3) Dehydroepiandrosterone.
4) Dihydrotestosterone.
5) Testosterone.
B. Estrogens:
1) Estradiol.
2) Estriol.
3) Estrone.
C. Progestogens:
1) Progesterone.
The most important hormones are Testosterone, Estradiol and
Progesterone.
In general, androgens are considered "male sex hormones", while
estrogens, and Progestogens are considered "female sex hormones"
although all types are present in each sex, but in different levels.

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A-Male sex hormones (Testosterone)
It is a steroid hormone that released from testis, it also released with
small amount from ovaries and adrenal gland ( cortex).
It is the principal male sex hormones and it is anabolic hormones.
 In Male:
1) In fetal development:
- Play a role in the determining the gender of developing fetus.
2) In puberty:
a. Play an important role in the development of secondary
sexual characteristics of male such as increase muscles and
bone mass, growth of facial and body hair, deeping of voice,
growth of Adam's apple……..etc.
b. Play an important role in the development of primary sexual
characteristics of male such as development of male
reproductive tissue such as testis and prostate.
c. Stimulate spermatogenesis.
d. Increase metabolic function in men and prevent
osteoporosis.
 In female:
a. It has a powerful anti-aging effect.
b. Increase bone mineral density.
c. Keeps skin supple.
d. Boots ability to handle stress.

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Testosterone production controlled by the releasing of luteinizing
hormone (LH). That comes from anterior lobe of pituitary gland.
Measurement:
The measurement of testosterone is done to assay:
 In men:
 Early or late puberty in boys.
 Impotence and infertility in men.
 In women :
 Excess hair growth (Hirsutism).
 Male body characteristics (Virilzation).
 Irregular menstrual periods.
Abnormalities:
 Increase production of testosterone indicate
a. Androgen resistance.
b. Congenital adrenal hyperplasia.
c. Ovarian cancer.
d. Testicular cancer.
 Decrease production of testosterone indicate:
a. Testicular failure.
b. Chronic diseases.

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What Causes Low Testosterone?
As a man ages, the amount of testosterone in his body naturally gradually
declines. This decline starts after age 30 and continues throughout life.
Some causes of low testosterone levels are due to:
 Injury, infection, or loss of the testicles
 Chemotherapy or radiation treatment for cancer
 Genetic abnormalities such as Klinefelter's Syndrome (extra X
chromosome)
 Hemochromatosis (too much iron in the body)
 Dysfunction of the pituitary gland (a gland in the brain that produces
many important hormones) or hypothalamus
 Inflammatory diseases such as sarcoidosis (a condition that causes
inflammation of the lungs)
 Medications, especially hormones used to treat prostate cancer and
corticosteroid drugs
 Chronic illness
 Chronic kidney failure
 Cirrhosis of the liver
 Stress
 Alcoholism
 Obesity (especially abdominal)

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What Are the Symptoms of Low Testosterone?
Without adequate testosterone, a man may lose his sex drive,
experience erectile dysfunction, feel depressed, have a decreased sense of
well-being, and have difficulty concentrating.
What Changes Occur in the Body Due to Low Testosterone?
Low testosterone can cause the following physical changes:
 Decrease in muscle mass, with an increase in body fat
 Changes in cholesterol levels
 Decrease in hemoglobin and possibly mild anemia
 Fragile bones (osteoporosis)
 Decrease in body hair
 Changes in cholesterol and lipid levels

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B-Female sex hormones (Progesterone):
-It is a steroid hormone involved in the female menstrual cycle,
pregnancy and embryogenesis of humans.
-Progesterone is produced in the ovaries (by the corpus luteum), the
adrenal glands, and during pregnancy, in the placenta.
-In humans, increasing amounts of progesterone are produced during
pregnancy:
 At first, the source is the corpus luteum that has been "rescued"
by the presence of human chorionic gonadotropins (hCG).
 After the 8th week, production of progesterone shifts to the
placenta.
1. Menstruation
2. Maturing follicle
3. Mature follicle
4. Ovulation
5. Corpus luteum
6. Deterioration of corpus luteum.

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Function of Progesterone hormone:
 Reproductive system:
1. Progesterone prepare the uterus for implantation.
At the same time progesterone affects the vaginal
epithelium and cervical mucus, making it thick and
impenetrable to sperm. If pregnancy does not occur,
progesterone levels will decrease, leading, in the human, to
menstruation.
2. During implantation and gestation, progesterone
appears to decrease the maternal immune response to
allow for the acceptance of the pregnancy.
3. Decreases contraction of the uterine muscles.
4. inhibits lactation during pregnancy.
 Progesterone is the precursor to other steroid hormones like
testosterone and estrogen.

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Progesterone Measurements:
 Determine if a woman is ovulating.
 Evaluate a women with repeated miscarriages (spontaneous
abortion).
 Determine the risk of miscarriage or ectopic pregnancy early in
pregnancy.
Normal result:
Progesterone levels vary depending on when the test is done. Blood
progesterone levels start to rise midway through the menstrual cycle,
continue to rise for about 6 to 10 days, and then fall if fertilization does
not occurs.
Levels continue to rise in early pregnancy.
This following are normal ranges based upon certain phases of the
menstrual cycle and pregnancy:
 Female (pre-ovulation): less than 1 ng/Ml
 Female (mid-cycle): 5 to 20 ng/mL
 Male: less than 1 ng/mL
 Postmenopausal: less than 1 ng/mL
 Pregnancy 1st trimester: 11.2-90.0 ng/mL
 Pregnancy 2nd trimester: 25.6-89.4 ng/mL
 Pregnancy 3rd trimester: 48.4-42.5 ng/mL

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Abnormalities:
A-Higher-than-normal levels may be due to:
a. Pregnancy.
b. Adrenal cancer.
c. Ovarian cancer.
d. Congenital adrenal hyperplasia.
B-Lower-than-normal levels may be due to:
a. Amenorrhea.
b. Ectopic pregnancy.
c. Failure to ovulate.
d. Fetal death.
e. Possible miscarriage.

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Estrogens
-They are the primary female sex hormones. Natural estrogens are
steroid hormones some synthetic ones are non-steroidal.
-The three major naturally occurring estrogens in women are estrone
(E1), estradiol (E2), and estriol (E3).
-Estradiol is the most important one.
Estrogens are produced primarily by:
i. Developing follicles in the ovaries,
ii. The corpus luteum.
iii. Placenta.
Estrogens are also produced in smaller amounts by other tissues such as
the liver, adrenal glands, and the breasts. These are the sources of
estrogens especially in postmenopausal women.
 In Female:
1. - Promote the development of female secondary sexual
characteristics, such as breasts.
2. - Regulate the menstrual cycle.
3. - Stimulate endometrial growth
4. - Increase fat stores.
5. - Reduce muscle mass.
 In Male:
1. Regulates certain functions of the reproductive system.
2. Important to the maturation of sperm.

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Estrogen production stimulated by Follicle-stimulating hormone (FSH).
Abnormalities:
1-In Women:
 ↑ Estrogen ( Hyperestrogenimia) duo to :
i. Exogenous administration of estrogen.
ii. Pregnancy.
This causes ↑ risk of:
i. Thrombosis.
ii. Stroke.
iii. Dementia ( in postmenopausal women > 65 year).
iv. Myocardial infarction.
v. Invasive breast cancer.
vi. Endometrial cancer.
2-In men:
Excessive production of estrogen give rise to feminization (development
of female secondary sexual characteristics) such as: enlargement of
breast, loss of facial hair,…..etc.
Medical applications:
 Oral contraceptives (Birth-control pills).
 Cosmetics (Some hair shampoos on the market include estrogens
and placental extracts).

Hormons of endocrain in body of humen pat

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