endocrinology

What is endocrinology? 

-  endon (within) + krinein (separate)

-  A science dealing with the endocrine glands.
 
-  The science of the endocrine system 

Endocrine system (classic definition):
•	ductless glands
•	secrets hormones into the blood
•	acts on distant targets
•	regulates a pre-existing cellular activity;   coordinates the activities of various tissues to maintain "systemic homeostasis"
•	minimal overlap of biological activities ( deficiencies cause marked abnormalities)

-  Modern (broad) definition of endocrinology:  the study of the adjustments of homeostatic and other activities accomplished by chemical messengers.

I. 	HOMEOSTASIS  

The physical and chemical characteristics of the environment to which cells are directly exposed must be compatible with the survival of the cells.  For example:

-  Temperature
-  Nutrients
-  Oxygen
-  Pressure
-  Ion concentrations
-  pH
-  Toxic chemicals

1.  Unicellular organisms:  	- directly exposed to external environment

The physical and chemical characteristics of the external environment must be compatible with the survival of the cells.  

Unicellular organisms do not have effective mechanisms to change the external environment

2.  Multicellular organisms:	-  external environment
-  individual cells exposed to the internal environment (milieu interieur;  Claude Bernard) = extracellular fluid (i.e.,  blood plasma + interstitial fluid)

In multicellular organisms, the physical and chemical characteristics of the internal environment must be compatible with the survival of the cells.  

Multicellular organisms are capable of regulating the physical and chemical characteristics of the internal environment.
Homeostasis:  	maintaining the stability of the internal environment within a narrow (“physiological”) range (W.B. Cannon)
(homeo = “same”  stasis = “to stand or stay”)

Generation of the internal environment:  each cell contributes to it.

Maintaining the stability of the internal environment:  preventive and restorative function
a coordinated physiological process
most of the organs contribute to it by:

-  exchanges between the internal and external environments
-  exchanges between the internal and intracellular environments

Coordination:	by feedback systems, mainly negative feedback mechanisms

sensory mechanisms  detect changes in internal environment
integrative mechanisms  evaluate 
effector (motor) mechanisms  carry the command to the organs

    nervous system:  rapid, precise changes, esp. muscular and secretory functions
•	endocrine system:  slower and longer lasting changes, esp. metabolic functions
•	immune system

The three control systems are intertwined

Major homeostatic variables controlled by the endocrine system:

-  osmolarity (ADH)

-  ion levels
calcium (parathormone, calcitonin, vitamin D)
sodium (aldosterone, atrial natriuretic peptide)
potassium (aldosterone)
hydrogen (aldosterone)

-  water balance  pressure (vasopressin, ANP, aldosterone)

-  glucose levels (insulin, glucagon)

-  CH, fat and protein metabolism (leptin, thyroid h., growth h., sex h., insulin, etc.)

-  nervous system 
autonomic n.s., e.g., thermoregulation (prostaglandins, thyroid h., neuropeptides)
cognitive functions
behavior, e.g., feeding, drinking, vigilance

-  immune system
immunostimulation by prolactin, growth h., melatonin
immunosuppression by glucocorticoids

II. 	Sexual differentiation, growth, development, aging

growth hormone, thyroid hormones, sex hormones

III. 	Reproductive processes

Behavior:	courtship, mating, maternal behavior

Local effects on specific organs:	development of the follicle
uterine changes (menstrual cycle)
maintenance of pregnancy
initiation of labor
milk secretion and ejection

chemical messengers

Hormones (modern, broad definition):  any substance that is released by a cell and acts on another cell (to regulate its function). The means of intercellular communication.

This definition includes:
-  Gap junctions:  direct flow of various chemicals from one cell to another
-  Autocrines
-  Paracrines (in the nervous system:  neurotransmitters, neuromodulators)
-  Endocrines (the "classic hormones")
-  Pheromones

SITE OF hormone production

I. 	endocrine glands  
          secretory cells
connective tissue
blood vessels
no duct
innervation and vascularization (fenestrated capillaries)

One gland can produce several types of hormones - same hormone can be produced by various glands

Endocrine glands  Exocrine glands (exo = “outside”)
secrete enzymes, waste products, etc. NOT hormones
NOT into the bloodstream
several organs have both endocrine and exocrine glands (e.g., pancreas, gut)
II. 	ISOLATED SECRETORY CELLS

III.  EXTRACELLULAR FLUID (PLASMA)

hormone-producing organs/tissues

-  pituitary
-  pineal gland
-  thyroid
-  parathyroid
-  adrenals
	-  ovaries
-  testes
-  pancreas
-  thymus
	-	hypothalamus
-	kidney
-	liver
-	intestines
-	lung
-	heart
-	adipose tissue
-	placenta
-	blood
-	skin	

Pituitary (hypophysis)				
Adenohypophysis (anterior pituitary)				
Growth hormone	GH			
Prolactin	PRL			
Follicle-stimulating hormone	FSH			
Luteinizing hormone	LH			
Melanocyte stimulating hormone	MSH			
Thyroid-stimulating hormone	TSH			
Adrenocorticotropic hormone	ACTH			
-Lipotropin	-LPH			
Neurohypophysis (posterior pituitary)				
Vasopressin (antidiuretic hormone)	ADH			
Oxytocin				
				
Hypothalamus				
Releasing hormones				
Growth hormone-releasing hormone	GHRH			
Thyrotropin-releasing hormone	TRH			
Corticotropin-releasing hormone	CRH			
Gonadotropin-releasing hormone	GnRH			
Inhibiting hormones				
Somatostatin	SST			
Prolactin-inhibiting hormone (dopamine)	PIH			
				
Thyroid gland				
Triiodothyronine	T3			
Thyroxine	T4			
Calcitonin				
Parathyroid gland				
Parathormone	PTH			
Adrenal gland				
Adrenal cortex				
Aldosterone (mineralocorticoids)				
Cortisol (glucocorticoids)				
Dehydroepiandrosterone (androgens) 	DHEA			
Adrenal medulla				
Epinephrine (adrenaline)	E (A)			
Norepinephrine (noradrenaline)	NE (NA)			
Dopamine	DA			
Ovary				
Estradiol (estrogens)	E2			
Progesterone				
Relaxin				
Placenta				
Chorionic gonadotropin	hCG			
Estriol (estrogens)	E3			
Progesterone				
Chorionic somatomammotropin				
Testis				
Testosterone				
Inhibin				
Pineal gland				
Melatonin				
Thymus				
Thymosin				
Pancreas				
Insulin				
Glucagon				
Somatostatin	SST			
Pancreatic polypeptide	PP			
Gastrointestinal tract				
Secretin				
Cholecystokinin	CCK			
Gastrin				
Gastric inhibitory peptide	GIP			
Vasoactive intestinal peptide	VIP			
Glucagon-like peptide	GLP-1			
Liver				
Vitamin D				
Insulin-like growth factors	IGF			
Skin				
Vitamin D				

Kidney				
Erythropoetin				
Renin				
Vitamin D				
Heart				
Atrial natriuretic peptide	ANP			
Plasma				
Angiotensin II	Ag-II			
Lung				
Angiotensin I	Ag-I			
Adipose tissue				
Leptin				
Various tissues				
Prostaglandins	PG			
Prostaglandin D2	PGD2			
Prostaglandin E2	PGE2			
Growth factors				
Nerve growth factor	NGF			
Epidermal growth factor	EGF			
Fibroblast growth factor	FGF			
Opioids				
-Endorphin				
Enkephalins	Enk			
Cytokines				
Interleukins	IL			
Interferons	IFN			
Tumor necrosis factors	TNF			
Granulocyte-macrophage colony                                   stimulating factor	
GM-CSF			

SITE OF HORMONE ACTION

I. 	tropic hormones

Primary function: 	regulation of hormone secretion by another endocrine gland, e.g., hypothalamic trophic hormones, TSH, ACTH, etc.

II. 	NONTROPIC HORMONES

Primary function:	modulate the function of  nonendocrine target tissues, e.g., T4, mineralocorticoids, glucocorticoids, insulin, etc.

Endocrine hierarchies:

Hypothalamus

Pituitary

Peripheral endocrine gland (e.g., adrenal gland;  “HPA axis”)

Amplification!

Chemical classification of “classic” hormones 

Chemical structure determines:  solubility and transport characteristics
degradation rate (plasma half-life)
storage
route of exogenous administration

I. 	Peptides

Structure:	chains of amino acids
amino terminal (N-terminal) and carboxy terminal (C-terminal) ends
linear - ring - two chains - carbohydrate residues (= glycoproteins)
Solubility:	hydrophilic
Synthesis:	rough ER, packaged in Golgi complex
Storage:	secretory granules
Secretion:	exocytosis
Transport:	mostly as a free hormone
Receptor site:	surface of target cell
Action:	channel changes or second messenger system

II. 	Amines

1.  Catecholamines (dopamine, epinephrine, and norepinephrine)
Structure:	tyrosine derivative
Solubility:	hydrophilic
Synthesis:	cytosol
Storage:	secretory (chromaffin) granules
Secretion:	exocytosis
Transport:	as a free hormone and bound to plasma proteins
Receptor site:	surface of target cell
Action:	second messenger system

2.  Thyroid hormones 
Structure:	iodinated tyrosine derivative
Solubility:	lipophilic
Synthesis:	extracellular colloid
Storage:	extracellular colloid
Secretion:	endocytosis of colloid
Transport:	mostly bound to plasma proteins
Receptor site:	inside of target cell
Action:	direct effects on genes  production of new proteins

III. 	
Steroids (mineralocorticoids, glucocorticoids, sex hormones, and vitamin D)

Structure:	cholesterol derivatives
lipids, steroid ring (3 six-membered and 1 five-membered ring)
Solubility:	lipophilic
Synthesis:	stepwise modification of cholesterol molecule in various intracellular compartments (in the endocrine gland and also in the blood and target tissues)
Storage:	hormones not stored, only precursor (cholesterol) stored
Secretion:	diffusion
Transport:	mostly bound to plasma proteins
Receptor site:	inside of target cell
Action:	direct effects on genes  production of new proteins

studying endocrinology:  points to ponder

I. 	description of individual hormones

1. 	Chemical characteristics
2. 	Source (anatomy and histology of the gland)
3. 	Major effects of the hormone
4. 	Regulation of the hormone secretion (which factors stimulate and which suppress its production)
5. 	Endocrinopathies
a) 	causes and symptoms of decreased secretion, name of the disease(s)
b)   causes and symptoms of increased production, name of the disease(s)

II.   integrative endocrine regulation

Interaction among various hormones in the regulation of complex physiological functions (e.g., cardiovascular and metabolic effects, regulation of development, etc.)