Editing Endocrinology (section)

== History ==
[[File:Arnold Adolph Berthold.gif|thumb|150px|[[Arnold Adolph Berthold|Arnold Berthold]] is known as a pioneer in endocrinology.]]
The earliest study of endocrinology began in China.<ref name="genius" /> The Chinese were isolating sex and pituitary hormones from human [[urine]] and using them for medicinal purposes by 200 BC.<ref name="genius">{{cite book|last=Temple|first=Robert|title=The genius of China: 3,000 years of science, discovery & invention|date=2007|orig-year=1986|publisher=Andre Deutsch|location=London|isbn=978-0-233-00202-6|pages=141–145|edition=3rd}}</ref> They used many complex methods, such as sublimation of steroid hormones.<ref name="genius" /> Another method specified by Chinese texts—the earliest dating to 1110—specified the use of [[saponin]] (from the beans of ''[[Gleditsia sinensis]]'') to extract hormones, but [[gypsum]] (containing [[calcium sulfate]]) was also known to have been used.<ref name="genius" />

Although most of the relevant tissues and endocrine glands had been identified by early anatomists, a more humoral approach to understanding biological function and disease was favoured by the [[Ancient Greece|ancient Greek]] and [[Ancient Rome|Roman]] thinkers such as [[Aristotle]], [[Hippocrates]], [[Lucretius]], [[Aulus Cornelius Celsus|Celsus]], and [[Galen]], according to Freeman et al.,<ref>{{cite journal |author=Freeman ER|author2=Bloom DA|author3=McGuire EJ |title=A brief history of testosterone |journal=Journal of Urology |volume=165 |issue=2 |pages=371–3 |date=2001 |pmid=11176375 |doi=10.1097/00005392-200102000-00004 }}</ref> and these theories held sway until the advent of [[germ theory of disease|germ theory]], physiology, and organ basis of pathology in the 19th century.

In 1849, [[Arnold Adolph Berthold|Arnold Berthold]] noted that castrated cockerels did not develop combs and wattles or exhibit overtly male behaviour.<ref>{{cite journal | author = Berthold AA | date = 1849 | title = Transplantation der Hoden | journal = Arch. Anat. Physiol. Wiss. Med. | volume = 16 | pages = 42–6 }}</ref> He found that replacement of testes back into the abdominal cavity of the same bird or another castrated bird resulted in normal behavioural and morphological development, and he concluded (erroneously) that the testes secreted a substance that "conditioned" the blood that, in turn, acted on the body of the cockerel. In fact, one of two other things could have been true: that the testes modified or activated a constituent of the blood or that the testes removed an inhibitory factor from the blood. It was not proven that the testes released a substance that engenders male characteristics until it was shown that the extract of testes could replace their function in castrated animals. Pure, crystalline [[testosterone]] was isolated in 1935.<ref>{{cite journal | author = David K| author2 = Dingemanse E| author3 = Freud J| date = 1935 | title = Uber krystallinisches mannliches Hormon aus Hoden (Testosteron) wirksamer als aus harn oder aus Cholesterin bereitetes Androsteron | journal = Hoppe-Seyler's Z Physiol Chem | volume = 233 | issue = 5–6| pages = 281–283 | doi = 10.1515/bchm2.1935.233.5-6.281 |display-authors=etal}}</ref>

[[Graves' disease]] was named after Irish doctor [[Robert James Graves]],<ref>{{WhoNamedIt|doctor|695|Robert James Graves}}</ref> who described a case of [[goiter]] with [[exophthalmos]] in 1835. The German [[Karl Adolph von Basedow]] also independently reported the same constellation of symptoms in 1840, while earlier reports of the disease were also published by the Italians Giuseppe Flajani and Antonio Giuseppe Testa, in 1802 and 1810 respectively,<ref>{{WhoNamedIt|doctor|1471|Giuseppe Flajani}}</ref> and by the English physician [[Caleb Hillier Parry]] (a friend of [[Edward Jenner]]) in the late 18th century.<ref>{{cite journal |author=Hull G |title=Caleb Hillier Parry 1755–1822: a notable provincial physician |journal=Journal of the Royal Society of Medicine |volume=91 |issue=6 |pages=335–8 |date=1998 |pmid=9771526 |pmc=1296785 |doi=10.1177/014107689809100618}}</ref> [[Thomas Addison]] was first to describe [[Addison's disease]] in 1849.<ref>{{cite journal |author=Ten S|author2= New M|author3=Maclaren N |title=Clinical review 130: Addison's disease 2001 |journal=Journal of Clinical Endocrinology & Metabolism |volume=86 |issue=7 |pages=2909–22 |date=2001 |doi= 10.1210/jcem.86.7.7636|pmid=11443143 |url=http://jcem.endojournals.org/cgi/content/full/86/7/2909 |doi-access=free }}</ref>
[[File:ThomasAddison.jpg|thumb|150px|[[Thomas Addison]]]]
In 1902 [[William Bayliss]] and [[Ernest Starling]] performed an experiment in which they observed that acid instilled into the [[duodenum]] caused the [[pancreas]] to begin secretion, even after they had removed all nervous connections between the two.<ref>{{cite journal | last1=Bayliss | first1=W. M. | last2=Starling | first2=E. H. | title=The mechanism of pancreatic secretion | journal=The Journal of Physiology | publisher=Wiley | volume=28 | issue=5 | date=1902-09-12 | issn=0022-3751 | pmid=16992627|  pmc=1540572| doi=10.1113/jphysiol.1902.sp000920 | pages=325–353}}</ref> The same response could be produced by injecting extract of jejunum mucosa into the jugular vein, showing that some factor in the mucosa was responsible. They named this substance "[[secretin]]" and coined the term ''hormone'' for chemicals that act in this way.

[[Joseph von Mering]] and [[Oskar Minkowski]] made the observation in 1889 that removing the [[pancreas]] surgically led to an increase in [[blood sugar]], followed by a coma and eventual death—symptoms of [[diabetes mellitus]]. In 1922, Banting and Best realized that homogenizing the pancreas and injecting the derived extract reversed this condition.<ref>{{cite journal |author=Bliss M |title=J. J. R. Macleod and the discovery of insulin |journal=Quarterly Journal of Experimental Physiology |volume=74 |issue=2 |pages=87–96 |date=1989 |pmid=2657840 |doi=10.1113/expphysiol.1989.sp003266 |doi-access=free }}</ref>

[[Neurohormone]]s were first identified by [[Otto Loewi]] in 1921.<ref>Loewi, O. ''Uebertragbarkeit der Herznervenwirkung.'' Pfluger's Arch. ges Physiol. 1921;189:239-42.</ref>  He incubated a frog's heart (innervated with its [[vagus nerve]] attached) in a saline bath, and left in the solution for some time. The solution was then used to bathe a non-innervated second heart. If the vagus nerve on the first heart was stimulated, negative [[inotropic]] (beat amplitude) and [[chronotropic]] (beat rate) activity were seen in both hearts. This did not occur in either heart if the vagus nerve was not stimulated. The vagus nerve was adding something to the saline solution. The effect could be blocked using [[atropine]], a known [[Enzyme inhibitor|inhibitor]] to [[heart]] vagal nerve stimulation. Clearly, something was being secreted by the [[vagus nerve]] and affecting the heart. The "vagusstuff" (as Loewi called it) causing the myotropic (muscle enhancing) effects was later identified to be [[acetylcholine]] and [[norepinephrine]]. Loewi won the Nobel Prize for his discovery.

Recent work in endocrinology focuses on the molecular mechanisms responsible for triggering the effects of [[hormone]]s. The first example of such work being done was in 1962 by [[Earl Wilbur Sutherland Jr.|Earl Sutherland]]. Sutherland investigated whether hormones enter cells to evoke action, or stayed outside of cells. He studied [[norepinephrine]], which acts on the liver to convert [[glycogen]] into [[glucose]] via the activation of the [[phosphorylase]] enzyme. He homogenized the liver into a membrane fraction and soluble fraction (phosphorylase is soluble), added norepinephrine to the membrane fraction, extracted its soluble products, and added them to the first soluble fraction. Phosphorylase activated, indicating that norepinephrine's target receptor was on the cell membrane, not located intracellularly. He later identified the compound as cyclic AMP ([[Cyclic adenosine monophosphate|cAMP]]) and with his discovery created the concept of second-messenger-mediated pathways. He, like Loewi, won the Nobel Prize for his groundbreaking work in endocrinology.<ref>{{cite journal |author=Sutherland EW |title=Studies on the mechanism of hormone action |journal=Science |volume=177 |issue=4047 |pages=401–8 |date=1972 |pmid=4339614 |doi= 10.1126/science.177.4047.401|bibcode = 1972Sci...177..401S }}</ref>