slide set 3 part 1 (cell communication and integration/ homestasis chap.6 and 7)

• 80% due to differences in concentration and permeability of key ions
• 20% dues to Na and K pump (3Na outside and 2K inside)

resting potential = -70mV

• achieve and maintain homeostasis
• the 2 systems are connected and work as 1 system called the Neuroendocrine system

• Functions
• communications
• integration
• control

some near release neurohormones instead of neurotransmitters

in the endocrine system, secreting cells send hormone molecules via the blood to specify cells contained in target tissues or target organs

• effects of neurotransmitters = rapid and short lived
• effect of hormones = slow and longer lasting
• hormones can diffuse in the blood and can therefore access most tissues and cells
• neurons can only stimulate muscles and glands across a synapse

are "ductless glands" made of glandular epithelium whose cells manufacture and secrete hormones

• endocrine glands = secrete hormones
• exocrine glands = secrete products

a few endocrine glands are made of neurosecretory tissue

glands of endocrine system are widely scattered throughout the body

Hypothalamus = controls release of anterior pituitary hormones

• Anterior pituitary
• 1. TSH = stimulates thyroid cells to produce thyroxine (T4) and triiodothyronine (T3)
• 2. ACTH = stimulates cortisol secretion from adrenal cortex
• 3. Growth hormone = growth and metabolic effects
• 4. FSH and LH = act on gonads, growth follicles, ovulation, Leydig cell stimulation of testosterone, FSH in male, androgen binding protein expression by Steroli cells
• 5. Prolactin milk = synthesis from mammary glands

• Posterior pituitary
• 1. Vasopressin = antidiuretic that acts on kidneys
• 2. Oxytocin = lets down milk and uterine contractions

• Pineal glands
• melatonin = entrains biological rhythm

• Thyroid glands
• produces T3 and T4
• cacitonin to decrease plasma controls how quickly the body burns energy and makes proteins
• metabolism regulator

• Adrenal cortex
• aldosterone = acts on kidneys to conserve Na, overall retention of water
• cortisol =  ↑ BP and blood sugar and ↓ reduces immune responses (anti inflammatory)

• Adrenal medulla
• epinephrine and norepinepherine = stress adaptation

• Pancreas
• insulin, glucagon, stomatostatin = nutrient levels and utilization

• Gonads
• sperm and egg

• iodine = essential for production of thyroxine
• lacking = causes goiter
• children with thyroid hormone deficiency will have physical growth and development problems, brain development will be severely impacted causing cretinism

cretinism = stunted physical and mental growth

• Hydrophilic hormones
• water soluble
• most are peptide or protein hormones 
• ex. insulin from pancreas or catecholamines (adrenal hormones, ex. epinephrine)

• Lipophilic hormones
• have ↑ lipid solubility and are poorly water soluble (lipid soluble)
• include thyroid hormones and steroids
• all steroids are derived from cholesterol, ex. cortisol from adrenal cortex and sex hormones
• thyroid hormone is an exception as it is an iodinated tyrosine (aa) derivative

• Water soluble = circulate in "free" form
• amine
• peptide/protein
• eicosanoid**

• Lipid soluble = use transport proteins
• steroid
• thyroid
• nitric oxide (NO)

eicosanoids acts as paracrine factors

• Arachidonate
• released from glycerophospholipids (phospholipase A2)

• Prostaglandins
• smooth muscle contractions(labor)
• regulate blood flow
• regulate body temperature

• Thromboxanes
• produced in platelets
• involved in blood clotting

• Leukotrienes
• airway smooth muscle contractions

• Tropic hormones
• target other endocrine glands 
• stimulate growth and secretion of other hormones
• ex. TSH targets the thyroid

• Sex hormones
• target reproductive tissues

• Anabolic hormones
• stimulates anabolism (to build) in target cells
• ex. testosterone stimulates protein synthesis and build up of cellular tissues, especially in muscle

• the solubility proteins of a hormone determine:
• 1. the means by which the hormone is processed by the endocrine cell
• 2. the way the hormone is transported in the blood
• 3. the mechanism by which the hormone exerts its effect signalling

• Hydrophilic peptide
• hormone precursors - preprohormones
• they are made in the ribosome of the ER
• in the Golgi, they are converted to pro hormones and finally active hormones
• these hormones are released from endocrine cells to exocytosis

• Lipophilic
• cholesterol is the common precursor for all steroid hormones (except thyroid hormone)
• only the precursor, cholesterol, is stored

the lipid soluble hormone is not stored (metabolized by liver) or excreted in the urine

• all are made form cholesterol
• all have 4 ring steroid nucleus
• at their core
• ex. cortisol, aldosterone, estrogen, progesterone, testosterone

• all are made from amino acids
• some are protein hormones = long, folded chains of amino acids
• ex. insulin

• Glycoprotein hormone
• are protein hormones with carbohydrate groups attached to the amino acids
• ex. hCG

• Peptide hormones
• smaller than protein hormones
• short chain amino acids 
• ex. oxytocin and antidiuretic hormone (ADH)

• Amino acid derivative hormones
• each is derived from a single amino acid
• ex. Amine hormone = made from a single molecule of tyrosine
• made by neurosecretory cells and by neutrons
• ex. epinepherine and noepinepherine (adrenal medulla)
• ex. amino acid derivatives produced by the thyroid gland made by a dying iodine to tyrosine

Combined hormone actions:

• Synergism (2 hormones better than 1)
• combinations of hormones acting together have a greater effect on the target cells than if they were to act alone
• ex. FSH and estrogen act on granolas cells

• Permissiveness
• when a small amount of a hormone allows a 2nd one to have full effect on a target hormone

• Anatagonism 
• one hormone does the opposite of another
• ex. parathyroid hormone ↑ Ca and calcitonin ↓ Ca

• hormones signal a cell by binding to the target cells specific receptors in a "lock n key" mechanism
• diffrent hormone receptor interactions produce different regulatory changes within target cells through chemical reactions
• ex. activation of an enzyme
• ex. initiation of gene transcription

• sensitivity of the target cell depends on the number of receptors that cell has
• hormone receptors are constantly broken down and replaced
• this process provides new receptors and a level of control when new receptors can be incorporated an transcription ↑

• Up- regulation
• ↑ number of hormone receptors ↑ sensitivity
• hormones often regulate own receptor levels

• Down - regulation
• ↓ number of hormone receptors ↓ sensitivity

• 1. direct contact
• 2. cell to cell

paracrine and autocrine = chemical signals

• Autocrine signals
• act on the same cell that secreted them

• Paracrine signals
• are secreted by one cell and diffuse to adjacent cells

Long distance communication

• hormones are secreted by endocrine cells or cells in the blood
• only target cells with receptors for the hormone will respond to the signal

• Neurotransmitters
• secreted by neutrons that diffuse across a small gap to the target cell
• neutrons use electrical signals as well
• neurotransmitters = rapid effect

• 1. signal molecule binds to the receptor protein
• 2. the receptor protein activates intracellular signal molecules
• 3. intracellular signalling molecules will alter target proteins
• 4. target proteins will create a response

• membrane spaning proteins
• cytoplasmic talk linked to G protein, a 3 part transducer molecule

• When G proteins are activated they
• open ion channels in the membrane
• alter enzyme activity on the cytoplasmic side of the membrane

• 1. signalling molecule binds to G protein linked receptor, which activate the G protein
• 2. G protein turns on adenylyl cyclase, an amplifier enzyme
• 3. adenylyl cyclase converts ATP → cyclic AMP (cAMP)
• 4.cAMP activates protein kinase A 
• 5. Protein kinase A phosphorylates other proteins and results in a cellular response

• 1. signal molecule activates receptor and associated G protein
• 2. G protein activates phospholipase C (PL-C), an amplifier enzymes
• 3. PL-C converts membrane phospholipids (PIP2) into diacylglycerol (DAG) which remains in the membrane  and IP3, which diffuses in the cytoplasm
• 4. DAG activates kinase C (PK-C) which phosphorylates proteins
• 5. IP3 = causes release of Ca++ from organelles, creating a Ca++ signal

EX. OXYTOCIN