Endocrinology

Endocrinology

I.	Endocrine System

	1.	One of the Body's Communication Systems

		A.	Other is Nervous System
		B.	Homeostasis Regulation

	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

	3.	Modes of Transmission

		A.	Endocrine

			a.	Gland to Blood to Target
			b.	Classical Mode

		B.	Exocrine

			a.	Secreted through duct to "exterior" of body
			b.	Exterior can be urinary, reproductive, 
				or digestive tract lumen

		C.	Paracrine

			a.	Cell to Cell
			b.	Interstitial Fluid

		D.	Autocrine

			a.	Cell to itself
			b.	Interstitial Fluid

		E.	Neurocrine

			a.	Involving nerve cells
			b.	Synapse or into blood stream

		F.	Epicrine

			a.	Cell to Cell
			b.	Without going into body fluids
			c.	Gap Junctions
			
		G.	Intracrine

			a.	Cell to itself
			b.	Without going into body fluids	



	4.	Structure

		A.	Amines

			a.	Derived from Tyrosine or Tryptophan (amino acid)
			b.	Thyroid hormone, epinephrine, dopamine, etc.

		B.	Peptides

			a.	Polypeptides and proteins
			b.	Insulin, FSH, GH, ADH, etc.

		C.	Steroids

			a.	Derived from Cholesterol
			b.	Estrogen, Progesterone, Testosterone, 
				Glucocorticoids, Aldosterone, Vitamin D, etc.

		D.	Fatty Acids

			a.	Derived from Arachidonic Acid
			b.	Prostaglandins



        5.	Other Characteristics of Hormones

		A.	Act at very low concentrations

			a.	Found in picogram to nanogram per ml 
				concentrations in blood
			b.	Parts per billion or trillion

		B.	Have short half lives in blood

			a.	Degraded after action on target
			b.	Disallows further and/or unnecessary action
			c.	Half life increased by glycosylation 
				(sialic acids)

		C.	Regulate intracellular biochemical reactions 
			at targets

			a.	Usually involved in some type of secretory 
				action of a cell

	6.	General Physiological Processes
	
		A.	Modulate cellular synthesis and secretion of other hormones
		B.	Modulate metabolic processes
		C.	Affect contraction, relaxation, and metabolism of muscle
		D.	Control reproductive processes
		E.	Modulate cellular proliferation
		F.	Regulate exretion and reabsorption of inorganic cations and anions
		G.	Modulate effect of other hormones
		H.	Modulate behavior

	7.	Mechanisms of Hormone Action

		A.	The interaction between a hormone 
			and its specific receptor on a target tissue 
			results in the physiological response 
			of the hormone

			a.	Location of hormone receptors

				i.	Plasma membrane
				ii.	Cytoplasm
				iii.	Nucleus

			b.	Numbers of receptors on a target cell 
				can change

				i.	As cell changes in developmental 
					or differentiation states
				ii.	By up-regulation
				iii.	By down-regulation

		B.	Membrane receptors

			a.	Used by peptide, amino acid, or fatty acid 
				hormones

			b.	Receptor binding causes activation 
				of second messenger system

				i.	cAMP
				ii.	cGMP
				iii.	Tyrosine kinase
				iv.	Ca++ 

			c.	Cascade of enzyme reactions eventually 
				causes activation of transcription factors 
				to stimulate (or inhibit) transcription of 
				mRNA from DNA

		C.	Nuclear (and cytoplasmic) receptors

			a.	Primarily steroid hormones

				i.	Thyroid Hormone (amine), Vit. A and D also 
					belong to this family

			b.	Lipophilic steroid diffuse though plasma 
				(and nuclear) membranes where they bind to 
				a specific receptor in the cytoplasm 
				or nucleus

				i.	All steroids have nuclear receptors
				ii.	Not all steroid hormones have 
					cytoplasmic receptors

			c.	Receptor binding causes a conformational 
				change that allows the hormone-receptor 
				complex(es) to interact with nuclear 
				chromatin as a transcription factor

				i.	Whether hormone-receptor complex 
					interacts with the nuclear chromatin 
					as a monomer or dimer may effect 					
					the physiological responses



	8.	Factors that effect physiological activity (strength) 
		of hormones

		A.	Pattern and duration of secretion

			a.	Episodic

				i.	Pulsatility (Amplitude and Frequency)

			b.	Basal (tonic)

				i.	Baseline
				ii.	Still Pulsatile

			c.	Sustained

				i.	Increase in baseline 
					for longer period of time

		B.	Half-life

			a.	Degradation
			b.	Clearance rate from blood

		C.	Receptor density

			a.	Number of receptors per cell

		D.	Receptor-hormone affinity

			a.	How tight hormone binds
			b.	Agonist

				i.	Analog to hormone 
					--Similar structure
				ii.	Same biological action
				iii.	Sometimes stronger affinity 
					and greater activity	

			c.	Antagonist

				i.	Also analog
				ii.	Inhibits action of native hormone
					--Stronger affinity, 
						less or no activity
					--Lesser affinity, but get in way 
						of native hormone


II.	Pituitary Gland
	

	1.	Called "Master Gland" since many important hormones 
		are secreted from pituitary

	2.	Posterior Pituitary

		A.	Oxytocin

			a.	Milk letdown
			b.	Uterine Contractions

		B.	ADH

			a.	Fluid Balance

		C.	Synthesized in hypothalamus, 
			secreted by posterior pituitary

	3.	Anterior Pituitary

		A.	Growth Hormone (GH) or Somatotropin (ST)

			a.	Acts on all tissues that can grow

				i.	Long Bones
				
			b.	Metabolic Effects

				i.	Increase Protein Synthesis
				ii.	Increase Fatty Acid Mobilization
				iii.	Decrease Glucose Uptake

			c.	Mediated by Somatomedins from liver 

				i.	Also called insulin like growth 
					factors (IGFs)

		B.	Adrenal Corticotropic Hormone (ACTH)

			a.	Acts on Adrenal Cortex to stimulate 
				steroidogenesis

				a.	Glucocorticoids
				b.	Mineralocorticoids

		C.	Prolactin (PRL)

			a.	Acts on Mammary Gland
			b.	Luteotropic agent (rodents)
			c.	Maternal Behavior?

		D.	Thyroid Stimulating Hormone (TSH)

			a.	Acts on Thyroid to release thyroid hormones

		E.	LH and FSH

			a.	Acts on Gonads 
			b.	Reproductive Functions

		F.	Melanocyte Stimulating Hormone (MSH)

			a.	Skin Pigmentation

	4.	All pituitary hormones are peptides

	5.	Synthesis and secretion of anterior pituitary hormones 
		is modulated by Releasing and/or Inhibiting Factors 
		from the hypothalamus.

		A.	Examples

			a.	GnRH--LH and FSH Release
			b.	Dopamine--Prolactin Inhibition

III.	Thyroid and Parathyroid Glands

	1.	Located on Trachea

	2.	Thyroid Hormones

		A.	Thyroxine (T4) and Triiodothyronine (T3) (amines)

			a.	Increase Oxygen Consumption by Cells
			b.	Increase Metabolism

		B.	Calcitonin

			a.	Decrease Calcium in Blood
			b.	Decrease Bone Reabsorption
			c.	Increases Calcium Loss by Kidney

	3.	Parathyroid

		A.	Located near or embedded in Thyroid

		B.	Parathyroid Hormone (peptide)

			a.	Increase Calcium in Blood
			b.	Increase Bone Reabsorption
			c.	Increase Calcium Reabsorption by Kidney
			d.	Increase Vitamin D activation in Kidney

				i.	Increase Ca++ and PO4++ absorption 
					by intestine


IV.	Adrenal Gland

	1.	Located cranial to the kidney

	2.	Adrenal cortex hormones (steroids)

		A.	Glucocorticoids (Cortisol)

			a.	Increase Glucose Biosynthesis
			b.	Increase Diuresis
			c.	Anti-inflammatory

		B.	Mineralocorticoids (Aldosterone)

			a.	Increase Na+ reabsorption
			b.	Increase K+ excretion

	3.	Adrenal medulla hormones (amines)

		A.	Epinephrine (Adrenaline)

			a.	Increase Metabolism

		B.	Norepinephrine

			a.	Increase Metabolism
			b.	Neurotransmitter (Sympathetic)


V.	Pancreas

	1.	Located behind stomach between duodenum and spleen

	2.	Endocrine Function from Islets of Langerhans

		A.	Alpha Cells--Glucagon
		B.	Beta Cells--Insulin
		C.	Delta Cells--Somatostatin

	3.	Pancreatic Hormones (Peptides)

		A.	Insulin

			a.	Increase glucose transport into cells
			b.	Production of glycogen in liver
			c.	Increase Lipogenesis
			d.	Increase protein synthesis
			e.	Decrease Blood Glucose

		B.	Glucagon

			a.	Increase Blood Glucose
				--Reverse effects of insulin
			b.	Increase insulin and somatostatin

		C.	Somatostatin

			a.	Slows nutrients into circulation
			b.	Moderates metabolic effects by insulin, 
				glucagon, and GH
			c.	Also hypothalamic inhibiting factor 
				for somatotropin
				
VI.	Gonads

	1.	Testis
		
		A.	Androgens (Testosterone and DHT)
			a.	Produced by Leydig (Interstitial) Cells
			b.	Stimulated by LH (ICSH)
			c.	Functions:
				i.	Maintains spermatogenesis
				ii.	Causes differentiation of the fetal male 
					reproductive tract and testicular descent
				iii. 	Maintains Libido (Sex drive)
				iv. 	Maintains secretory activity of the 
					accessory glands
				v. 	Maintains secondary male 
					sexual characteristics
				vi.	Protein Anabolism	

		B.	Peptide Hormones
			a.	Produced by Sertoli cells
			b.	Inhibin
				--Feedback on pituitary to decrease FSH 
			b.	Activin
				--Feedback on pituitary to increase FSH 
			c.	Androgen Binding Protein
				--Maintain Androgens in Testis
				
	2.	Ovary
		
		A.	Estrogen
			a.	Produced primarily by Follicle
			b.	Mostly under control of FSH
			c.	Functions:
				i.	Stimulate endometrial gland growth
				ii.	Stimulate duct growth in the mammary gland
				iii.	Increase secretory activity of the 
					reproductive ducts
				iv.	Initiation of sexual receptivity
				v.	Regulation of LH and GnRH by the anterior 
					pituitary and hypothalamus
				vi.	Early union of the epiphysis with the 
					shafts of long bones, ceasing growth of 
					long bones
				vii.	Bone Maintenance	
				viii.	Protein anabolism
				ix.	Vaginal epithelium proliferation and 
					cornification
					
		B.	Progesterone
			a.	Produced by Follicle and Corpus Luteum
			b.	Mostly under control of LH
			c.	Functions:
				i.	Promotion of endometrial gland growth
				ii.	Stimulation of secretory activity of the 
					oviduct and endometrial glands to provide 
					nutrients for the developing embryo prior 
					to implantation
				iii.	Promotion of alveolar growth in the 
					mammary gland (w/ estrogen)
				iv.	Prevention of contraction of the uterus 
					during pregnancy

		C.	Peptide Hormones
			a.	Inhibin
			b.	Activin
			c.	Others
			
	3.	Gonadal Steroid and Peptide Hormones responsible 
		for feedback regulation of Hypothalamic-Pituitary-Gonadal Axis
				

VII.	Prostaglandins

	1.	Derived from Arachidonic Acid

	2.	Produced by almost all tissues

	3.	Functions:

		A.	Luteolytic agent (PGF2alpha)
		B.	Decrease Gastric Secretion
		C.	Relax Bronchial Smooth Muscle
		D.	Decrease Platelet Aggregation (PGI2)
		E.	Increase Platelet Aggregation (Thromboxane A2)
		F.	Vasoconstriction (PGF2alpha)
		G.	Vasodilation (PGE2)


VIII.	Growth Factors

	1.	Peptides

	2.	Produced by many organs and tissues

	3.	Besides growth these factors have 
		many physiological activities

	4.	Common Growth Factors

		A.	Insulin-like Growth Factors (IGF)
		B.	Epidermal Growth Factors (EGF)
		C.	Fibroblast Growth Factors (FGF)
		D.	Platelet-Derived Growth Factors (PDGF)
		E.	More discovered all the time
		
IX.	Other Endocrine Organs

	1.	Kidneys
		A.	Erthropoietin
			a.	Low Oxygen stimulates
			b.	Stimulates bone marrow 
				to produce new RBCs
		B.	Renin
			a.	Released during low blood pressure
			b.	Initiates Angiotensin II from liver
		C.	Vitamin D
			a.	Activated by PTH
			b.	Promotes Ca++ absorption from 
				intestine

	2.	Stomach
		A.	Gastrin
			a.	Stimulated by Food
			b.	Causes release of HCl and digestive enzymes
				from stomach.
			c.	Increases gastric motility
		
	3.	Small Intestines
		A.	Secretin
			a.	Causes pancreas to secrete bicarbonate to
				buffer acidic intestine contents
			b.	Inhibit Gastric Activity
			c.	Stimulates Gall bladder
		B.	Cholecystokinin
			a.	Causes pancreas to release digestive enzymes
			b.	Inhibit Gastric Activity
			c.	Stimulates Gall bladder
			
		
	4.	Placenta
		A.	Steroid Hormones
			a. Estrogen
			b. Progesterone
		B.	Peptides
			a.	Chorionic Gonadotropins
				i.	Pregnancy maintenance and diagnosis
			b.	Relaxin
				i.	Softening of Pubic symphysis
			c.	Placental Lactogens
				i.	Immune function
				ii.	Fetal Growth
				iii.	Initiation of Lactation.
			d.	More
			
	5.	Thymus
		A.	Thymosin and Thymopoetin
			a.	T-lymphocyte production
			b.	Cell-mediated immunity
		
	6.	Pineal Gland
		A.	Melatonin
			a.	Controls seasonal breeders
		
	7.	Liver
		A.	Angiotensin II
			a.	Regulates Fluid balance
		B.	Insulin-like Growth Factors
			a.	Mediates Growth Hormone Action
			b.	Initiates lactation
		C.	Others.