Iendocrinology.com

I. DESCRIPTIVE PERIOD

II. PERIOD OF ANALYTICAL ENDOCRINOLOGY

III. CONTEMPORARY PERIOD/SYNTHETIC ENDOCRINOLOGY

Gonads and liver were known to earliest physicians

1400 BC…Ayurveda documents Hindus knew that pregnancy lasts for 10 lunar months

sealing spirits are responsible for infertility

Contraceptive methods too hypothized in Ayurveda..

I. Swallowing three year old molasses or roots of Agni tree cooked in sour rice water

II. Vaginal fumigation with smoke of Neem wood or passiveness in coitus/holding breath

III. Coitus obstructus or smearing of vagina with honey/ ghee or vaginal medication of rock salt dipped in oil

Goiter is described as GALAGANDA For cure of impotence and obesity

administration of testicular tissue (ORGANOTHERAPY)

INFERTILITY“THOUSANDS OF GOLD PRISCRIPTION” BY SON SSU MO 695AD

Dried placenta to improve fertility

Abortion: a pill (oil & quick silver) fried and taken empty stomach

The oldest reports about iodine deficiency and more specifically Goitre come from China. As much as 5000 years ago

Treatment-seaweed. Nowadays it is known that people who

eat a lot of seaweed do not suffer from iodine deficiency.

Signs of sterility: women having spots before their eyes

Diagnostic test for pregnancy: watermelon pounded mixed with milk of woman who has born son is given

a) if the woman vomits- she is pregnant b) if only flatulence - never bear again

Contraception: Ovariotomy were performed

Carvings of patients with Acromegaly, Goitre and Achondroplasia have been unearthed

Eunuchs /Castrated males in ancient times were used to guard harems

STATUE THE SKULL- MUMMY

CLEAOPATRA (69 BC) CONSIDERED TO BE SYMBOL OF BEAUTY(MIDDLE AGES)

ALEXANDRIANS-III CENTURY BC-THYMUS

GALEN -GREEK(AD 129 – 200) THYROID, PINEAL&PITUTARY

BARTOLOMMEO EUSTACHI-SUPRARENALS-16TH CENTURY

PAUL LANGERHANS (1847-1888)-INSULA OF PANCREAS -1869

1880-Ivar Viktor Sandstorm , swedish medical student,described parathyroid

It was the last major organ to be recognized in humans

17th century William Harvey describes heart as a four chambered pump that moves blood through arteries and veins, not air.Mid 1800s idea that circulating blood carries substances from one part of the body to a distant part where the substance exerts its effect.

1766- Ruysch: Internal secretory function of endocrine organs “Haller text book of physiology”

1801-Le Callois.1836-T Wilkinson King: Thyroid secretion

1840- George Gulliver: Adrenal secretion

JOHN HUNTER(1728 – 1793)-1792

ARNOLD ADOLPH BERTHOLD ( 1 803-1 86 1 ) -1849

Castration of cock caused atrophy of comb but this could be prevented if the testis were transplanted to another part of the body

CONCEPT OF INTERNAL SECRETION-ESTABLISHED IN SCIENTIFIC KNOWLEDGE

THE GREAT TRIUMVIRATE

1855-the glycogenic function of the liver; in the course of this he was led to the conclusion, which throws light on the causation of diabetes mellitus, that the liver, in addition to secreting bile, is the seat of an internal secretion, by which it prepares sugar at the expense of the elements of the blood passing through it “lessons on experimental physiology”

1855- “Constitutional And Local Effects Of Disease Of Supra Renal Capsule”Role of internal secretion is demonstrated through anatomical observations1.Addison’s disease2.Addison’s crisis3.Addisonian anemia/pernicious anemia4.Adrenoleukodystrophy, etc

1855- Demonstrated that removal of the adrenal gland resulted in death, due to lack of essential hormones.

1856- Alfred Vulpian : discovered adrenaline /chromogen in the adrenal medulla

1895- Eugene Baumann: iodothyroxine as active principle in thyroid

1901- Takamine & Aldrich: independently isolated secretion of adrenal medulla and described chemical structure as “adrenaline”

1902- Bayliss and Starling isolated secretin from duodenal secretion

1905-ERNEST H STARLING1904-MAURICE-ADOLPHE LIMON

First used the term “ endocrine/endocrinology”

Endo= Greek adjective; inside

First to use the word hormone at royal college of physicians, in his Croonian lectures , HARMAO = GREEK VERB;HAVING PROPERTY OF STIMULATING

HARVEY WILLIAMS CUSHING "FATHER OF MODERN NEUROSURGERY".

Discovery of the integration of glands and their regulatory process

Pitutary gland and its regulatory actions- Harvey Cushings,Longdon-Brown

1918- L.Greving, 1933-Roussy & Mossinger- demonstrated nervous connections between hypothalamus and pituitary gland, olfactogonadal& opticogonadal reflex arc

1931- Walter Cannon: adrenaline “fight or flight response”

1923- John Macleod : insulin

1904: T R Elliot- sympathetic nervous system and release of chemicals, in 1921 Cannon and Loewi termed it as adrenal hormone

1906-Dixon,1921-Loewi, 1929-Dale: parasympathetic nerves act through cholinergic hormone

HIPPOCRATES(460 BC –  370 BC) – DISEASE OF SCYTHS: HYPO-ORCHADISM/CLIMATIC HYPOOVARISM

HYPOTHYROIDISM-EARLIEST TO STUDIED

1850- TB Curling:described role of

thyroid in symptom complex of cretinism

1871- Hilton-Fagge related the Cretinoid state to a congenital inadequacy of thyroid function in early childhood.

1873 -Gull related dry skin, sparse hair, puffiness of the face and hands, and a swollen tongue to Myxedema, the pathological deficiency of thyroid function in adults (goiter).

1855-the first person to correctly connect the symptoms of what is now called ADDISON’S DISEASE to a functional deficiency of the adrenal glands

1889- BROWN SEQUARD:  Hypodermic injection of a fluid prepared from the testicles of guinea pigs and dogs, as a means of prolonging human life

1890- G R M URRAY: Thyroid organotherapy

1921- insulinotherapy by Banting, later sex hormones, cortins, growth hormone etc

Insulin 1926- One of the first proteins to be

crystallized in pure form. 1955 - First protein to be fully

sequenced 1958 - First protein to be chemically

synthesized in – though in insufficient quantities to be produced commercially

1979 – First human protein to be manufactured by way of Biotechnology

1869- Paul Langerhans, a medical student in Berlin, identified some previously un-noticed tissue clumps scattered throughout the bulk of the pancreas.

The function of the "little heaps of cells," later known as the islets of langerhans, was unknown

Edouard luaguesse later suggested that they might produce secretions that play a regulatory role in digestion.

Paul Langerhans' son, Archibald, also helped to understand this regulatory role.

1889- Oscar Minkowski in collaboration with  Joseph Von Mering removed the pancreas from a healthy dog to test its assumed role in digestion.

Several days later Minkowski's animal keeper noticed a swarm of flies feeding on the dog's urine.

On testing the urine they found –sugar Establishing for the first time a

relationship between the pancreas and diabetes.

1901-  Eugene Opie, established the link between the Islets of Langerhans and diabetes

 ”Diabetes mellitus … is caused by destruction of the islets of Langerhans and occurs only when these bodies are in part or wholly destroyed. .”

1906- George Ludwig Zuelzer was partially successful treating dogs with pancreatic extract but was unable to continue his work.

Between 1911 and 1912- E L Scott  at the university of Chicago used aqueous pancreatic extracts and noted a slight diminution of glycosuria but was unable to convince his director of his work's value; it was shut down. 

1919- Israel Kleiner demonstrated similar effects at  Rockfellar university, but his work was interrupted by  WW I and he did not return to it.

1921 - Nicolae Paulescu, a professor of physiology at the university of medicine and pharmacy in Bucharest was the first one to isolate insulin

called “Pancrein” Use of his techniques was patented

in Romania, though no clinical use resulted

1921 -Fedrick banting meet JJR MacLeod, who supplied Banting with a lab at the University of Toronto, an assistant (medical student Charles Best), and 10 dogs, then left on vacation during the summer of 1921.

Their method was tying a ligature (string) around the pancreatic duct, and, when examined several weeks later, the pancreatic digestive cells had died and been absorbed by the immune system, leaving thousands of islets.

They then isolated an extract from these islets, producing what they called ”isletin” (what we now know as insulin), and tested this extract on the dogs.

Banting and Best were then able to keep a pancreatectomized dog alive all summer because the extract lowered the level of sugar in the blood

December 1921- Macleod invited the Biochemist James Collip, to help with this task, and, within a month, the team felt ready for a clinical test

 January 11,1922, Leonard Thompson, a 14-year-old diabetic who lay dying at the Toronto general hospital, was given the first injection of insulin. However, the extract was so impure that Thompson suffered a severe allergic reaction, and further injections were canceled.

Over the next 12 days, Collip worked day and night to improve the ox-pancreas extract, and a second dose was injected on the 23rd. This was completely successful, not only in having no obvious side-effects, but in completely eliminating the glycosuria sign of diabetes.

 young girl aged 13 years suffering from diabetes. She weighs just 45lbs and her chances of surviving for much longer are very, very poor. She was one of the first patients to be treated with insulin extracted from the pancreases of slaughtered cattle. 

spring of 1922- Best managed to improve his techniques to the point where large quantities of insulin could be extracted on demand, but the preparation remained impure.

The drug firm Eli Lilly and company had offered assistance not long after the first publications in 1921, and they took Lilly up on the offer in April.

November,1922- Lilly made a major breakthrough, and were able to produce large quantities of highly refined, 'pure' insulin. Insulin was offered for sale shortly thereafter.

1950’-The amino acid structure of insulin was characterized in the 1950's and

1977-the first genetically-engineered human insulin was produced in a laboratory in 1977 by Genentech using E. Coli. 

1982-Partnering with  Genentech , Eli Lilly went on in 1982 to sell the first commercially available human insulin under the brand name Humulin.

1923-The Nobel Prize committee in 1923 credited the practical extraction of insulin to a team at the University of Toronto and awarded the Nobel Prize to two men; Frederick Banting and JJR Macleod.

Banting, insulted that Best was not mentioned, shared his prize with Best, and Macleod immediately shared his with James Collip.

The patent for insulin was sold to the University of Toronto for one dollar

The primary structure of insulin was determined by British molecular biologist  Frederick Sanger.

1958-It was the first protein to have its sequence be determined. He was awarded the 1958 Nobel prize in Chemistry for this work.

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