Jimma University
College Of Health Sciences
Department Of Biochemistry
COURSE TITLE: HORMONE $ BIO SIGNALING
SEMINAL PRESENTATION ON- HYPOTHALAMUS $
PITUITARY H
BY;- ABDLHAFIZE…RM0879/15 -0
SUBMITTED TO:-MR.TESFAYE ( MSC )

Objectives
•At the end of this chapter the students will able to:
–Identify some of the major Adrenal hormone
–List and explain the hormones of adrenal hormones along
with their abnormalities
–Understanding the mechanism action of adrenal steroid
hormones

Adrenal glands
Adrenal glands: two small, triangular-shaped glands located at the
upper portion of each kidney
It is composed of an outer cortex and an inner medulla
Outer cortex
◦ Outermost zona glomerulosa: Synthesis site of
mineralocorticoids
◦ Central zona fasciculata: Synthesis site of glucocorticoids
◦ Inner zona reticularis: Synthesis site of adrenal sex steroid
hormones
Inner medulla: Synthesis site of catecholamines.

Adrenal cortical steroid synthesis
The adrenal cortical steroid hormones are derived from the
cholesterol via a branched metabolic pathway

1.Glucocorticoid (Cortisol)
Cortisol is the principal glucocorticoids.
Target organ - every cell of the body
Effects
◦ Regulation of carbohydrate, protein and lipid metabolism;
maintenance of blood pressure and suppression of the immune
response
General characteristics
◦ Steroids, lipid-soluble, protein bound, slow effects

Regulation of cortisol secretion
Hypothalamic regulation: it produces cortico-tropin releasing
factor(CRF).
Pituitary regulation: it produces ACTH in response to CRF
Negative feed-back: cortisol has direct –ve feed back effect on
hypothalamus to decrease CRF & on pituitary to decrease secretion
of ACTH.
Effect of physiological stress on ACTH secretion: Physical & mental
stress can lead to increase cortisol secretion within minutes via
increase ACTH.

Glucocorticoid transport
The lipid-soluble glucocorticoids are transported in circulation bound to
carrier proteins
◦ Cortisol is 90-97% protein-bound
◦ Cortisol-binding globulin (CBG) – major transport protein
◦ Albumin
◦ Sex-hormone binding globulin (SHBG)
◦ Conditions that change the level of binding protein affect the level of
total hormone, but not of the biologically active free hormone
◦ Causes of increased CBG
◦ Estrogen, hyperthyroidism, etc.
◦ Causes of decreased CBG
◦ Malnutrition, chronic liver disease, etc.

Hypersecretion of cortisol
Cushing’s syndrome
◦ Clinical disorder that result from supraphysiological level of cortisol
in the circulation (hypercorticortisolism)
◦ The cause can be primary to the adrenal cortex (adrenal adenoma in
carcinoma) secondary to overproduction of ACTH (pituitary
adenoma) or an ectopic carcinoma that produce ACTH, eg carcinoma
of the lung.
◦ The diagnosis is confirmed by dexamethasone suppression test.
◦ Plasma ACTH levels are low in primary adrenal disease and high
when there is uncontrolled production of ACTH by a neoplasm.

Hyposecretion of cortisol
Adreno cortical insufficiency, evident by a low plasma cortisol
concentration
The causes may be:
◦ Primary to the adrenal cortex because of destruction of cortical
tissue by autoimmundisease or infection (addison’s disease) or
◦ Secondary to ACTH deficiency
The diagnosis is confirmed by finding a subnormal cortisol response to
the administration of exogenous ACTH (rapid ACTH stimulation test)

Serum cortisol measurement
Adrenocortical hormone tests are typically performed on blood plasma or 24-hour
urine samples.
Reference ranges for blood serum cortisol levels:
Adults (8 A.M.): 6-28 μg/dL;
adults (4 P.M.): 2-12 μg/dL.
Child 1-6 years (8 A.M.): 3-21 μg/dL;
child 1-6 years (4 P.M.): 3-10 μg/dL.
Reference ranges for urine (free cortisol):
Adult: 10-100 micrograms/24 hr.
Adolescent: 5-55 μg/24 hr.
Child: 2-27 μg/24 hr.

2.Mineralocorticoids (aldosterone)
Aldosterone: the principal mineralocorticoid hormone .
Target organs - kidneys, sweat and salivary glands and GI tract.
Effects: Aldosterone regulates electrolyte balance and extracellular fluid
balance .
◦ It regulates blood volume and blood pressure.
◦ In the kidney, aldosterone causes active sodium reabsorption,
potassium and hydrogen excretion and passive water reabsorption.

Aldosterone release
Three release stimulators
◦ Renin-angiotensin system (RAS) – primary stimulation
◦ Extracellular potassium and sodium
◦ ACTH
Aldosterone
Its production is primarily controlled by the renin-angiotensin system.
ACTH has a slight stimulatory effect on aldosterone synthesis, but this is
usually of no significance.

(Aldosterone ) Con..
Renin
 Protein produced by the juxtaglomerular apparatus of the kidney in
response to decreased renal pressure and/or decreased serum
sodium levels.
 Acts on angiotensinogen to produce angiotensin I which is
converted to angiotensin II by angiotensin converting enzyme.
 Angiotensin II is a potent vasoconstrictor and also stimulates
secretion of aldosterone by adrenal cortex.

Aldosterone control
Atrial natriuretic peptide
Plasma k+ level
Role of ACTH
Plasma Na+ level
Renin- angiotensin system
Aldosterone has negative feedback on the juxtaglomerular apparatus of
the kidney.

Hyperaldosteronism
Primary hyperaldosteronism (conn’s syndrome)
◦ It is overproduction of aldosterone due to the presence of an
aldosterone secreting adrenal adenoma.
◦ These patients usually have elevated serum Na+ concentration,
lowered K+ and hypertension.
Secondary hyperaldosteronism
◦ It result from abnormalliteis in the renin-angiotensin system
◦ It result from
◦ Excess production of renin→associated with increased
plasma renin

Hypoaldosteronism
Aldosterone deficiency is most often due to destruction of the adrenal
glands.
If sodium intake is not adequate, the patient will develop severe water
and electrolyte abnormalities and may die from vascular collapse
and/or hyperkalemia.

Laboratory diagnosis
Determination of aldosterone by RIA and FPIA
Determination of sodium and potasium in serum and urine
Two blood samples are often drawn for aldosterone evaluation, one in
the early morning and one mid-afternoon.
Because a 24-hour urine specimen reflects hormone production over an
entire day, it will usually provide a more reliable aldosterone
measurement.
Elevated blood levels should ideally be confirmed with a 24-hour urine
test.

Cont…
Results will also vary between patients depending upon average sodium
intake, time of day, source of specimen, age, sex, and posture.
Reference ranges for blood plasma levels: radioimmunoassay
◦ Supine: 3-10 ng/dL.
◦ Upright: Female: 5-30 ng/dL; Male: 6-22 ng/dL
◦ Urine: 2-80 micrograms/24 hr.

3.Catecholamines
Catecholamines – epinephrine, norepinephrine and dopamine.
◦ Epinephrine is the major adrenal catecholamine (80-90%)
◦ Affects metabolism (mobilizes energy stores) and increases heart rate
and blood pressure in times of stress
◦ Functions as a neurotransmitter
◦ Norepinephrine (10-20%) and dopamine function solely as
neurotransmitters
Catecholamine adrenal release is stimulated by stressors such as fear and
pain.

Adrenal catecholamine synthesis
The adrenal medullary catecholamines are derived from the amino acid
tyrosine.

4.Gonadal hormones(Sex steroids)
Predominately produced by the adult male testes and female ovaries
Adrenal cortex also produces small amounts of sex steroids
Responsible for
◦ manifestation of primary and secondary sex characteristics
◦ Human reproduction
Characteristics – steroid, lipid-soluble, slow effects, bound to carrier
proteins (SHBG, albumin)
Their secretion is under hypothalamus-pituitary-gonadal axis control

Classes of female sex steroids
Androgens
◦ Dehydroepiandrosterone (DHEA), DHEAS, testosterone,
dihydrotestosterone (DHT), androstenedione
◦ The predominate adrenal androgens are DHEA and DHEAS
Estrogens
◦ Estradiol, estrone
Progestins
◦ Progesterone

Female sex hormones
Two different chemical types of steroid hormones are produced and
secreted by the ovary in non pregnant women.
◦ Estrogen and progesterone
During pregnancy, the same hormones are produced by the ovary, but
in different proportion.
The placenta also makes the hormones that are necessary for the
maintenance of pregnancy.
◦ Estrogen, progesterone, HCG, lactogen
This production is under control of
◦ hypothalamus(GnRH)→Pituitary(FSH,LH)→ovary/placenta
(female sex steroids)

Estrogen
Originate in the ovarian follicles and in the placenta during
pregnancy
Function
◦ Participate in the menstrual cycle
◦ development and maintenance of the reproductive organs and
secondary sex characteristics.
Three clinically important estrogens: C18 steroid
◦ Estradiol(E2): major hormone in non-pregnant
◦ Estrone(E1)
◦ Estriol(E3): major hormone in pregnant

Estradiol
The principal and most potent estrogen
It exists in a reversible state with estrone (with weaker biologic action), but
it must be converted into E1 before it is degraded.
◦ Estradiol (E2) ↔ Estrone (E1) → Estriol(E3) → degradation
Plasma E2 levels
◦ Useful for the investigation of women with menstrual difficulties
To ascertain wether a problem is of pituitary or ovarian origin.
◦ Measurement of pituitary tropic hormones, FSH and LH

Estriol(E3)
It has no hormonal activity
Produced in relatively large quantity during the last trimester of
pregnancy by the placental conversion of fetal adrenal steroids.
Its concentration in urine or plasma of pregnant women provides
indication of fetal well being (fetoplacental viability)
◦ Sudden drop in estriol concentration or output is a danger signal of
fetoplacental dysfunction.

Progesterone
It is a C21 compound and chemically more closely related to the adrenal
steroids.
It is an intermediate in the production of adrenal steroids.
Formed in the corpus luteum, the body that develops from the ruptured
ovarian follicle.
Function
◦ Stimulates the uterus to undergo changes that prepare it for
implantation of the fertilized ovum,
◦ Suppresses ovulation and secretion of pituitary LH.
◦ If pregnancy occurs, the secretion of progesterone by the corpus
luteum and by the placenta suppresses menstruation for the
duration of the pregnancy.

Placental hormones
Function of placenta: providing nutrients to the developing embryo and
removing its waste products
Additionally in the pregnant women it serves as an endocrine organ
◦ Produce
◦ Estrogen
◦ Progesteron
◦ chorionic gonadotropin (hCG)
◦ lactogen.

Human chorionic
gonadotropin (hCG)
It is a glycoprotein composed of 2 chains, alpha and beta.
Alpha polypeptide chain is identical to the alpha chain on many
other hormones including TSH, LH and FSH.
The beta chain is unique in hCG so is the speciificity for
immunoassay techniques.
The action of hCG is similar to that of LH
◦ It stimulate the corpus luteum to produce progesterone.
◦ Progesterone helps to maintain the pregnancy by preventing
menstruation.

Clinical significance of hCG
For diagnosis of pregnancy
◦ The detection of hCG in urine or serum is the basis of current tests
for pregnacy.
◦ The most sensetive can detect pregnacy with in 5 to 7 days after
conception.
◦ The antibody used for quantitation of serum hCG should be specific
to β-hCG in order to avoid cross reactions,

Human placental lactogen
It is a protein hormone that is structurally, immunologically and functionally
very similar to growth hormone and prolactin
HPL appears to act in concert with HCG to stimulate estrogen and
progesterone synthesis by the corpus luteum.
It stimulates development of the mammary gland (similar to prolcatin)
Has somatotropin actions similar to those of growth hormone.
◦ it increases maternal plasma glucose levels and mobilization of free fatty
acids and promotes positive nitrogen balance.

Male sex hormones
The male gonads are the testes.
They have a double function:
◦ To produce and secrete the male hormone, testosterone
◦ To produce the spermatozoa
◦ Essential for fertilization of the ovum in the reproductive process.
The testes are part of a hypothalamic-pituitary-gonadal axis.
◦ FSH stimulate spermatogenesis,
◦ LH stimulate the production of testestrone by interstitial (Leydig’s)
cells.
◦ Both LH and FSH suppressed by high levels of testosterone

Testosterone
The most potent naturally occurring androgen.
Function
◦ Promote growth of secondary sex organs
◦ It causes growth and development of the male reproductive
system, prostate, and external genitalia.
◦ Promotes muscular and skeletal growth and is protein anabolic.
Transport
• 80% by plasma globulin
• 17% by albumin
• < 3% unbound, active hormone.

Testosterone cont’d
All of the testosterone in males is derived from the testes; the
contribution of the adrenal cortex is negligible.
Plasma testosterone levels are much lower in women, usually
only 5% of those found in men.
◦ Testosterone in women arise from the tissue conversion of
androgens.
Plasma testosterone concentration is a good way of studying
hypogonadism and hypergonadism.
The role of the pituitary has to be assessed to determine whether
an abnormality is primary to testes or secondary to an LH
deficiency or excess.

Testosterone cont’d
Increased concentration of testosterone
◦ Testicular carcinomas
◦ Abnormalities of pituitary gonadotropin of males
◦ In female
◦ Virilism: development of male physical characteristics(depening of
voice, breast atrophy, increased hair growth)
◦ Hirsutism: growth of body hair in male like pattern
Decreased plasma testosterone can be due to:
◦ Defects associated with testis
◦ Defects associated in pituitary
◦ Chromosomal abnormalities of sex hormones.

Methods of Sex Steroid
Analysis
Estrogens and testosterol
◦ RIA
◦ Reference Ranges vary with method and timing of female cycle
More useful if tested along with FSH and LH

THANKS!!!!!