Hormones, History, and Homeostasis




I.	Endocrinology

	1.	The study of hormones and their actions

	2.	Endocrine System

		A.	One of the Body's Communication Systems

			a.	Other is Nervous System
			b.	Homeostasis Regulation
                                                                                           Estradiol
	2.	Hormones

		A.	Classical Definition:	
		
			Chemical substances produced by specialized ductless 
			glands that are released in the blood and carried to 
			other parts of the body to produce specific regulatory effects.

		B.	Many hormone-like substances don't meet criteria

			a.	Prostaglandins
			b.	Growth Factors
			c.	Etc.

		C.	Broader Definition:	Physiological Chemical 
							Regulators

II.	History of Endocrinology

	1.	Ancient Times
	
		A.	General belief that organs such as heart, gonads, or brain 
			taken from animals or slain enemies might be eaten in order to
			improve ones health.
			
			a.	Carried over into early medicine--extract from healthy organ 
				used to treat a diseased organ
				
		B.	Hipocrates (460-357 B.C.)
			--Homeostasis
		
			a.	Health is conditioned by balance of four humors
				i.	Blood
				ii.	Black Bile
				iii.	Yellow Bile
				iv.	Phlegm
				
		C.	Aristotle (384-322)
			--Effects of Castration
		
			a.	Castration of men and animals practiced from early times
			b.	Aristotle compared the effects of castration on birds and men.
				i.	Showed testes are related to sexual characteristics 
					and reproductive capacity in males.
					
	2.	Pre-Twentieth Century
	
		A.	Berthold (1849)
			--First endocrine study suggesting a secreted "hormone"
			a.  Proposed testis secreted something into the blood to cause male characteristics
			b.	Testosterone not isolated until 1935	
		B.	Bernard (1855)
			--Control of Blood Glucose
			a.	Chemically caused liver to release glucose into blood.
		C.	Addison (1855)
			--First endocrine disease described from defect of a gland.
			a.	Adrenal deterioration
		D.	von Mering adn Minkowski (1889)
			--Gland removal study
			a.	Removal of Pancreas causes Diabetes Mellitus in dogs.
		E.	Murray (1891)
			--Hormone Replacement
			a.	Glycerin emulsion of sheep thyroids treats hypothyroidism in humans
	
	3.	Twentieth Century
		--All the major hormones isolated and studied
	
		A.	Takamine and Aldrich (1901)
			a.	Purification of Epinephrine (Adrenaline)
		B.	Bayliss and Starling (1905)
			--First use of term "hormone"
			a.	Secretin experiments
			b.	From Greek "hormon"=exciting, set in motion.
		C.	Banting and Best (1921, 1922)
			--Islets of Langerhans produce insulin
			a.	Islet extracts used to treat diabetes
		D.	Loewi (1921)
			--Nerves release "hormones"
			a.	Frog Heart studies identifying acetylcholine and norepinephrine
				--Neurotransmitters			
		E.	Allen and Doisy (1920-30s)
			--First Steroid Hormones isolated
			a.	Studied and isolated estrogens
		F.	Ascheim and Zondek (1927)
			--Pregnancy test
			a.	Urine from pregnant animals caused follicular growth
			b.	Chorionic Gonadotropin
		G.	Du Vigneaud (1953), Sanger (1954)
			--Amino acid structure of peptide hormones
			a.	Du Vigneaud--oxytocin, ADH
			b.	Sanger--Insulin
		H.	Jensen and Gorski (Early 1960s)
			--Discovery of steroid hormone receptors
			a.	Radiolabeled Estrogen
		I.	Berson and Yalow (1960)
			--Quantitative measurement of hormones
			a.	Radioimmunoassay
		J.	Sutherland et al. (1962)
			--Discovery of second messengers
			a.	Cyclic AMP
			b.	Also first evidence of membrane receptors
		L.	Levi-Montalcini and Cohen (1960s)
			--Discovery of Growth Factors
			a.	EGF and NGF
		M.	Guillemin and Schally (Late 1960s)
			--Discovery of Hypothalamic Release Factors
			a.	TRH and GnRH
			
							
III.	Homeostasis


	1.	A state of body equilibrium

		A.	How the body organs function together to maintain 
			a stable internal environment for the general 
			well-being of the body

		B.	Chemical and Physical Balance

	2.	Homeostatic mechanisms

		A.	Sensing and Compensating

			a.	Nervous system
			b.	Endocrine system

		B.	Negative Feedback

			a.	Primary mechanism maintaining homeostasis
				--Change in opposite direction of initial change

			b.	Components

				i. 	Controlled system
				ii.	Set Point
				iii.	Receptor
				iv.	Processing center		


		C.	Positive Feedback

			a.	Change in same direction of initial change
			
			b.	Not used to maintain homeostasis
				--Sometimes a part of a negative feedback loop
							
			c.	Important in certain physiological circumstances
				--Childbirth, "fight or flight" responses, 
					Ovulation Signal, etc.

IV.	Hormones and Homeostasis (Examples)

	1.	Glucose Homeostasis
		
		A.	Glucagon increases blood glucose
		
			a.	Low blood glucose stimulates Pancreatic alpha cells to release
			b.	Glucagon cause glucose release from liver glycogen stores
			
		B.	Insulin decreases blood glucose
		
			a. 	High blood glucose stimulates pancreatic beta cells to release
			b.	Insulin cause glucose uptake by liver and other cells (fat cells, etc).
			
		C.	Clinical Endocrinology
		
			a.	Lack of or decreased insulin, or insulin sensitivity 
				leads to diabetes mellitus
				
				i.	Type I, Juvenile onset
					--Genetic
				ii.	Type II, Adult onset
					--Genetic and/or Environmental (Life-style)
					
			b.	Diets
			
				i.	Popular diets (Atkins, South Beach, etc) are thought 
					to work in part by keeping glucagon up and insulin down.
				ii.	Glucagon also stimulates lipolysis and gluconeogenesis
			
	2.	Calcium Homeostasis
	
		A.	Parathyroid Hormone increases blood calcium

			a.	Low calcium stimulates parathyroid to release
			b.	Increase Bone Reabsorption
			c.	Increase Calcium Reabsorption by Kidney
			d.	Increase Vitamin D activation in Kidney
				--Increase Ca++ absorption by intestine
				
		B.	Calcitonin decreases blood calcium

			a.	High calcium stimulates thyroid to release
			b.	Decrease Bone Reabsorption
				--May be used as a treatment for osteoporosis
			c.	Increases Calcium Loss by Kidney
			
IV.	Neuroendocrine integration in Homeostasis

	1.	Sensory stimuli through receptors stimulate endocrine system
	
	2.	Examples:
		
		A.	Control of Water Balance
			a.	Osmoreceptors--Sodium Concentration
			b.	Baroreceptors--Blood Volume
			c.	Hormones--ADH, Angiotensin II, etc.
		B.	Control of Body Temperature
			a.	Temperature receptors
			b.	Hormones--Thryoid, Epinephrine, etc.
		C.	Control of Feeding Behavior
			a.	Glucostats
			b.	Hormones--Insulin, glucagon, etc.
		
V.	Hormones and Behavior

	1.	Sexual Behavior
		A.	Pheromone--External signals
		B.	Sex Steroid and peptides--Internal signals
	2.	Hormones and Homosexuality
		A.	May be due to fetal sex differentiation of the brain.
	
VI.	Hormones, Growth Regulation, and Cancer

	1.	Relationship between growth factors (protooncogenes) and oncogenes
	2.	Many cancers are exacerbated by hormones
		A.	Breast Cancer--Estrogen
		B.	Prostate Cancer--Androgens
			
		

ANS 426 Webpage


~~~~~Revised 8/10/04~~~~~ TAW