PHINMA-Cagayan

de Oro College
College of Allied
Health Sciences
Bachelor in Medical Laboratory Science
Clinical Chemistry II

Endocrine system consist of:

- ductless gland

- chemical regulators/hormones

Hormones - linked to messengers or signals that cause physiologic and chemical

processes involved in the maintenance of body equilibrium/homeostasis.

Regulates: human functions such as metabolism, growth & development, tissue

function and mood.

May be classified as Endocrine Hormones.

These are classic hormones which are characteristically secreted into the
bloodstream and reach target organs which are distant from the source of the
hormone.

PARACRINE HORMONES:

Reach their target within the same site by diffusing through the interstitial

fluid. Ex: cytokines produced by the cells in the IS.

AUTOCRINE HORMONES:

- hormones act back on the cells which act as the source of the hormones to
modulate their secretion or the intracellular processes involved.

Ex: prolactin - produced by the anterior pituitary gland.

NEUROCRINE HORMONES:

- hormones produced by neurons. Oftentimes, they are referred to as

neurohormones.

Ex: neurotransmitters - acetylcholine and dopamine

Other examples are antidiuretic hormone (ADH) and oxytocin produced by the
supraoptic and paraventricular nuclei of the hypothalamus.
CLASSIFICATION OF HORMONES

Based on functions:

1. Releasing hormones - hormones found in hypothalamus promote the secretion of

anterior pituitary hormones.

2. Inhibiting hormones - hormones from the hypothalamus or the gastrointestinal

tract suppress the secretion of another organ.

3. Tropic hormones - they stimulate the growth and activity of other endocrine
glands.

For example TSH from the anterior pituitary gland causes hypertrophy of the thyroid
gland.

4. Effector hormones - these are secreted by all endocrine glands other than the
anterior pituitary gland and the hypothalamus. They are the ultimate hormones
responsible for causing physiologic processes.

HORMONE PRODUCTION

● Many hormones are produced as parent or precursor molecules. Polypeptide

hormones are synthesized first as pre-hormones.

● Pre-hormones contain a leader sequence of amino acids called a signal

sequence.

● The signal sequence is cleaved from the pre-hormone after insertion into the
endoplasmic reticulum.

● Within the secretory vesicle, the resulting product called a prohormone is then
enzymatically cleaved to a smaller active hormone molecule.

● The secretory vesicle can either migrate to the cell membrane, fuse and
release its hormones, or remain in the cytoplasm of the cell as storage vesicle

● The storage vesicle provides the body with immediate access to the hormone
in time of increased demand.

● A very illustrative example of a hormone with this fate is the hormone insulin.

● It is synthesized in the B-cells of the pancreas as a pre-proinsulin which is then

processed to form the pro-insulin

● Pro-insulin is then cleaved by proteases to form the C-peptide and the active
insulin hormone
MECHANISM OF HORMONE ACTION
The following are prerequisites for a chemical function in physiological regulation:

Target cells must have specific receptors that combine with the regulatory molecule
(i.e., the hormone).

Combination of the receptor with the ligand (i.eThe hormone) must cause a specific
sequence of changes in target cells.

There must be a mechanism to quickly turn off action of the regulator (e.g., feedback
inhibition).

GROUP II HORMONES

● For polypeptide, glycoproteins and catecholamines their target receptors are

located on the extracellular side of the cell membrane since they cannot cross
it to enter the cell.

● This is very much understandable since these molecules are hydrophilic.

● Before physiologic change is effected, the hormone must first bind with
extracellular receptor

● Signal transduction, which is the conversion of this binding phenomenon into a

sequence of chemical reactions in the target cell, then occurs.

● Signal transduction is frequently done by a system of intramembrane proteins

called G protein (with several subunits e.g., a, b, and y units) and an enzyme
(adenyl cyclase) attached to the intracellular of the plasma membrane.

GROUP I HORMONES

● In contrast to group II hormones: steroids and thyroid hormones can diffuse

through the cell membrane and enter the cell.

● Inside the cell they interact with their intracellular receptors

● Depending on the hormone, these receptors may be located in the cytoplasm or

in the nucleus.

● For steroid they bind with an intracytoplasmic receptor

● The hormone-receptor complex produced then migrates to the DNA in the

nucleus of the cell at specific nucleotide sequences.

● Zinc participates in the by binding w/ the DNA binding site rich in cysteine
residues to optimize the interaction between the hormone-receptor complex
and the DNA.
● Synthesis of mRNA and protein is then initiated.
HORMONE SECRETION & REGULATION

- Before a hormone is synthesized and/or secreted, proper signals must be

received by the endocrine
- Among the types of signals that cause hormone secretion are
Neural signals
- Stimulates the cerebral cortex or neural centers by thoughts,
emotion, stress or circadian rhythm.
- Many of the hormones released by: hypothalamus & adrenal
medulla are regulated this way.
Change in plasma concentration of certain ions or compounds -
PTH is released in situations where the level of calcium is low. - On
the other hand, if plasma glucose level is high, insulin secretion is
stimulated.
Tropic Hormone
- Stimulate their target organs to secrete effector hormones
- ACTH, for example, stimulates the adrenal cortex to secrete
cortisol while TSH stimulates the thyroid gland to secrete T3 and
T4.
Variation in blood osmolality
- Secretion of ADH is very responsive to an inc. plasma osmolality
Presence of foods
- The release of hormones in the gastro-intestinal tract is stimulated
by the presence of food in situ.

I. Regulation by the CNS

- Apart from these signals, the secretion of hormones may be regulated at other
levels.
- The CNS releases neurotransmitters e.g., acetylcholine, dopamine, serotonin,
and GABA (y-amino butyric acid).
- For example, feelings of fear and anxiety can stimulate the sympathetic nervous
system.
- As a consequence the adrenal medulla releases epinephrine - This could
explain how anxiety or stress can disturb the regularity of the menstrual cycle.
-
II. Regulation by the hypothalamus
- The hypothalamus releases hormones that regulate the secretion of the anterior
pituitary gland.
III. Feedback systems
- Operates among hypothalamic, pituitary & target endocrine glands. -
Two basic types: negative feedback & positive feedback systems
Negative feedback
- The final hormone produced regulates its own secretion by inhibiting the
 secretion of one or more of the precursor hormones.
- The feedback system is concentration-dependent i.e., if the end product is in
high concentration in the plasma, it will inhibit the cascade; if low, inhibition is
removed.

Example of axis that operate in this manner are:

● Hypothalamo-pituitary-thyroid axis
● Hypothalamo-pituitary-adrenal cortex axis
● Hypothalamo-pituitary-gonadal axis

Positive feedback
- The final hormone produced in a cascade enhances or induces the initial
hormone and causes its own production to be increased.
- Example: the stimulation of the gonadotropin production during mid-menstrual
cycle by the increased levels of estrogen-17- ��
HYPOTHALAMUS
- A number of glands that signal each other in sequence is usually referred to as
an axis, for example, the hypothalamic-pituitary-adrenal axis.
- The hypothalamus is located in the third ventricle and is directly above the
pituitary.
- The pituitary is anatomically connected with the hypothalamus by the
infundibulum or pituitary stalk
- The hypothalamus contains neurosecretory cells that produce stimulating,
 releasing, and inhibiting neuropeptides or hormones.
- It is primarily concerned with modifying the secretion of hormones from the
anterior pituitary.
- The hypothalamus controls body temperature, hunger, thirst, fatigue, sleep and
circadian cycles.

● Hypothalamic hormones are enumerated as follows:

1. Corticotrophin-releasing hormone (CRH) - stimulates the release of ACTH and

other hormones e.g. beta-lipoprotein and ��-endorphins
2. thyrotropin-releasing hormone (TRH) - stimulates the release of TSH 3.
Gonadotropin-releasing hormone (GnRH) stimulates the release of FSH and LH
4. Prolactin-inhibiting factor (PIF) - which decreases the level of prolactin. This
factor has been found out to be Dopamine.
5. Prolactin-releasing factor (PRF) - stimulates the release of thyrotropin and
prolactin
6. growth-hormone -releasing hormone (GNRH) - increases the level of GH. It is
also known as Somatocrinin.
7. Growth-hormone-inhibiting hormone (GHIH) - decreases the level of GH. It is
also known as somatostatin
8. Melanocyte-inhibiting factor (MIF) - decreases the level of melanocyte
stimulating hormone
9. Antidiuretic hormone (ADH) - also known as arginine vasopressin. - It
increases the reabsorption of water from the glomerular filtrate and urine
and promotes vasoconstriction
10.Oxytocin - stimulates uterine muscle contraction and milk ejection reflex.
PINEAL GLAND

- Location: posterior wall of the 3rd ventricle of the cerebrum at the base of the
brain.
- Exact function is remain unknown
- It produces _____________ which is responsible for inhibiting the activities of
gonadotropins in lower vertebrates.
- Among the physiologic and pharmacologic functions of the this hormone in
humans are as follows:

1. Regulation of circadian rhythms axis

- Dec. level of melatonin during the day
2. Inhibition of pituitary-gonadal axis
- Dec. level of melatonin is needed for the maturation of gonads -
Inc. melatonin delays onset of puberty
3. Treatment of jet lag
4. Treatment of insomnia
- Elderly people usually have insomnia because they have low levels of
melatonin. Melatonin pills can stimulate sleep.
5. Antioxidant

● Melatonin is an amine derivative from amino acid Tryptophan.

● Serotonin is also a by product of melatonin metabolism.

● It acts as a neurotransmitter
● Its metabolite called 5-OHLAA is excreted in the urine and can be assayed
using urine as a sample.

● Serotonin is rich in platelets and GIT.

PITUITARY GLAND
- Or hypophysis is connected to the hypothalamus through the infundibulum or
pituitary stalk.
- It protrudes from the inferior surface of the brain and resides in a depression of
the sphenoid bone of the skull called the sella turcica.
 ➢ The posterior pituitary stores 2 hormones:
● Oxytocin
● ADH/AVP
- These hormones are synthesized by the neurosecretory cells of hypothalamus
but are only stored and secreted in the posterior pituitary. - Hypothalamic
hormones act on various types of cells in the anterior pituitary. - The classification
of these cells is based on the staining reaction: HEMATOXYLIN & EOSIN.
- These are:
● Acidophils: red with H&E
a. Somatotrophs - produces GH.
b. Lactotrophs or mammotrophs - products prolactin
● Basophils: stains blue in H&E
a. Thyrotrophs - produces TSH
b. Gonadotrophs - produces FSH & LH
● Chromophobes: dont stain with H&E
a. Corticotrophs - secretes ACTH
Anterior pituitary hormones help regulate their own secretion by a negative feedback
mechanism to the hypothalamus, thus inhibiting the release of the hypothalamic
hormones or factors.

This is called the short-loop negative feedback.

ANTIDIURETIC HORMONE

- stimulates the cells of the DCT and CD of the nephron to increase the
absorption of water.

- The action of ADH has a concentrating effect on the urine.

- Primary stimulus for ADH secretion is the increase in plasma osmolality. -

This stimulus is detected by osmoreceptors in the hypothalamus.

 - In case where ADH is deficient, urine output is increased (polyuria) and the
patient experiences increased thirst (polydipsia)

- ADH is also referred to as AVP because it can cause generalized

vasoconstriction and may help maintain blood pressure during traumatic
injuries.

LABORATORY ANALYSIS DETECTION of ADH is generally by radioimmunoassay

(RIA).

● Specimen of choice: plasma anticoagulated EDTA.

● Blood is centrifuged immediately after blood collection and plasma is removed

quickly from the cells.

● Plasma can be frozen but ADH levels deteriorate with prolonged storage.

● Plasma ADH concentration are reported in conjunction with the patient’s

plasma osmolality
Reference range for ADH:
Osmolality (mOsm/kg) ADH level (pg/mL)

270-280 <1.5

280-285 <2.5

285-290 1-5

290-295 2-7

295-300 4-12

● Low concentration of ADH are often misinterpreted since low normal and the
absence of ADH cannot be distinguished.

OVERNIGHT WATER DEPARTMENT TEST

● This is an indirect measure of ADH content.

● Water is withheld from the patient for 8 hrs.

● A series of timed blood and urine samples is then obtained as well as the
weight of the patient.

● The osmolalities of the samples are determined.

● Patients with ADH deficiency should show increasing serum osmolality and
decreasing urine osmolality over time tested.
 ● This is because as the plasma is filtered through the kidney a higher
percentage of water remains in the glomerular filtrate and urine instead of
being reabsorbed, as would normally occur with the action of ADH.

● This causes a concentrating effect on the plasma and a dilutional effect on the
urine.

● Patients with normal ADH responses should not have weight losses greater
than 3% and the decrease in water intake should stimulate the release of
ADH.

● The increased ADH causes normalizing adjustments in the serum osmolalities

(by increasing the amount of water reabsorbed from the urine), and values
remain within the reference range (275-295 mOsm/kg)

Prepared by: LggRMT