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Physio 2

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LECTURE NO-2

HISTORICAL BACKGROUND OF ENDOCRINOLOGY


 How did scientists first find out what endocrine glands do?
o Scientists first removed the gland and monitored the organism for
changes (like in hormone deficiency).
o Then scientists replaced the gland or gave an extract of the gland to
see if the abnormalities disappeared (like in replacement therapy).
o Then scientists implanted the gland or gave extract to a normal
individual to see the symptoms (like in hormone excess).
o Once a gland was identified as a source of hormones, extracts from
the gland were purified and a test was designed to calibrate the
activity of the hormone in another organism (known as a bioassay).
 The writings of Hippocratus and Aristotle as early as BC 460 to 322 contain
some information that their might be internal control over body functions
 First recorded endocrine experiment was published by Berthhold (1849). He
discovered castrated cockerels failed to develop their combs and wattles and
also failed to exhibit male behaviour. Replacement of one or both testes back
into abdominal cavity restored the lost function.
 In 1889, von Mering and Minkowski demonstrated that surgical removal of
pancreas from dog produced a disease later to be known as diabetes mellitus.
This led to the recognition of insulin in the control of diabetes mellitus in
man and dogs.
 In 1902, Canadian physiologists Bayliss and Starling discovered that a
substance liberated by small intestinal mucosa stimulate the pancreatic juice
flow. The active substance was named as secretin. They coined the word

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“hormone” (from the Greek "I arouse to activity" or "I excite") to this newly
discovered substance.
 Banting and Best (1921) isolated the potent pancreatic extract containing
insulin
 In 1949, Hench and co workers isolated a hormone from adrenal cortex-
cortisone or compound E that relieved some of the symptoms of rheumatoid
arthritis.
 In 1953, Simpson and Tait found that unidentified steroid present in adrenal
gland was aldosterone. In the same year, Sanger established the amino acid
sequence for insulin for which he bagged the Nobel Prize.
 In 1953, Du Vigneaud and his co-workers determined the structure of
oxytocin and vasopressin.
 In 1955, Harris provided the data suggesting that the release of pituitary
hormones was controlled by humoral factors of hypothalamic origin.
 In 1962, Earl Sutherland described the presence of cyclic AMP in biological
materials.
 In 1978, insulin was synthesized by a strain of genetically engineered E.coli.
 For the development of RIA for hormone analysis, Rosalyn Yalow received
the Nobel prize in 1978.
DEFINITION
 The term hormone means "to excite" or "arouse".
 Hormones are chemicals secreted at variable rates in response to external or
internal stimuli by an endocrine gland or a group of cells in very low
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concentrations (nanomolar to picomolar – 10 to 10 M) directly into the
blood for transport to some distant target organs/cells where they alter
already existing reactions but cannot initiate new reactions.

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CLASSIFICATION BASED ON CHEMICAL NATURE
 Hormones are chemically classified into the following categories
1. Amines - are derivatives of the amino acids tyrosine and tryptophan (e.g)
epinephrine, norepinephrine.
2. Iodionated aminoacids – (e.g) Thyroxine
3. Peptides - consist of chains of amino acids. Examples of small peptide
hormones are TRH and vasopressin
4. Proteins: Peptides composed of numerous amino acids are referred to as
proteins. Examples of protein hormones include insulin and growth
hormone.
5. Glycoprotein: More complex protein hormones bear carbohydrate side
chains and are called glycoprotein hormones(e.g) LH, FSH and TSH.
6. Steroids - derived from cholesterol and contains basic cyclopentano
perhydro phenantherene nucleus. (e.g) Estrogen, progesterone, cortisol.
Being non-polar, they are able to pass through the phospho-lipid membrane
of a cell and enter the cytoplasm .
7. Fatty acids derivatives - Eicosanoids - they are a large group of molecules
derived from Arachadonic acid. The principal groups of hormones of
this class are prostaglandins, prostacyclins, leukotrienes and
thromboxanes. These hormones are rapidly inactivated by being
metabolized, and are typically active for only a few seconds.
CHEMICAL CLASSIFICATION OF HORMONES
o Chemical structure determines ,solubility and transport characteristics
,degradation rate (plasma half-life),storage and route of exogenous
administration
Sn. Peptides Amines Steroids

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1. Solubility hydrophilic hydrophilic lipophilic
2. Synthesis rough ER, cytosol stepwise modification of
packaged in cholesterol molecule in
Golgi various intracellular
complex compartments (in the
endocrine gland , blood
and target tissues)
3. Storage secretory secretory hormones not stored, only
granules (chromaffin) precursor (cholesterol)
granules stored.
4. Secretion exocytosis exocytosis diffusion
5. Transport mostly as a as a free hormone mostly bound to plasma
free hormone and bound to proteins
plasma proteins
6. Receptor surface of surface of target inside of target cell
site target cell cell

7. Action: channel second messenger direct effects on genes for


changes or system (sms)
production of new
sms
proteins

PHYSIOLOGICAL CLASSIFICATION OF HORMONES


1. Hormones Regulating Energy Metabolism :Insulin, Glucagon,
Glucocorticoids, Epinephrine, ACTH, Thyroid
2. Mineral Metabolism:Aldosterone, Renin-Angiotensin II & Natriuretic
hormone, PTH, CT , Vitamin D3
3. Growth:GH, Insulin, Estrogen, Androgen, Somatostatin, Thyroxine and
Cortisol
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4. Reproduction: GnRH, FSH, LH /ICSH, Estrogen, Inhibin Progestrone,
Testosterone, Oxytocin, Prostaglandins and Relaxin, GnIH, Thyroxin,
Cortisol, Prolactin and Gonadocrnin
5. Milk Secretion: Prolactin, TSH, ACTH, GH, Glucocorticoid, Placental
Lactogen, Thyroxin, Insulin and Oxytocin
6. Blood Pressure:Renin-Angiotensin, Epinephrine, Norepinephrine,
Vasopressin, ACTH , Vasotocin, ADH and ANP
7. Water Balance: Vasopressin (ADH), Renin-Angiotensin, Glucocorticoids
& Insulin
8. Local Hormones:PGs, Histamine, Serotonin
9. Gut Hormones:Gastrin, Secretin, CCK, Gastric inhibitory peptide (GIP),
Vasoactive intestinal Polypeptide

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