organ produce hormone release circulation distant site
communicate w cell thorugh receptor = biochemical response
organ pufff hormone
- endocrine signaling
nerves pufff hormone
- neuroendocrine signaling
- paracrine signaling: adjacent
- autocrine signaling: same cell
Sex steps of communication by hormones
- Synthesis of hormone
- Release of hormone
- Transport of hormone: blood
- Detection of hormon by receptor
- Change in cellular metabolism = hormone-receptor interaction
- Removal of hormone: cellular response
**each step can be a point of REGULATION
Classic Endocrine Organs
BRAIN
1. Hypothalamus
2. Pituitary Gland
3. Thyroid and parathyroid Gland
HEART
4. Atrial Natruiretic Peptides (ANP)
ADRENAL GLANDS/KIDNEY
5. Cortex and medulla
PANCREAS
6. ISLETS OF LANGERHANS
OVARIES
TESTIS
Hypothalamic-Pituitary Signaling
Blood vessel = Hypothalamic-Hypophyseal Portal System
*hypophys- = anterior pituitary
6 different types of cells in anterior pituitary = each hormonal response w distinct receptor
Difference between Glycopriteins and Polypeptides and Steroids and Amines?
Gene that encodes them
Steroids and amines need to be biosynthesized
Synthesis of Proteins hormones
Hormone = secreted protein
- Genome encodes a longer protein then the mature protein bc theyre gonna get cleaved.
- If cleaved and too small, kidney is gonna pee it out
- so you got N-terminal prosequence thing thing
Steroid Hormone Structure and types
Four ring
- Cortisol
- Aldosterone
- Testosterone
- Estradiol: bones
Thyroid Hormone Structure and types
Derived from Tyrosine + iodinated
T3 and T4: Tetra/Tri-iodothyronine
*reverse T3 = not a thyroid hormone bc doesnt bind to thyroid receptor. bc need double ionation of proximal ring
Lock and Key Mechanism
physiological affinity and range
Properties of Hormone Receptors
- Specificity
- Affinity
- Saturability
- Mesureable Biological Effect: induce series of biochemical event
Receptor Regulation
- Upregulation: increase activity
- Downregulation: decrease activity
How do hormones create effects on target cells
- Direct: on cell membrane (uncommon)
= glucose-insulin - Intracellular: mediated by 2nd messenger
= cAMP - Intracellular: mediated by Genomic or Nuclear action
= change in gene transcription
= de Novo protein production
Pituitary Gland
- Adenohypophysis = anterior = endocrine tissue
- Neurohypophysis = posterior = neural tissue
- Outgrowth of Hypothalamus
- Secretes Oxytocin & Vasopressin
- Prohormones = Secretory Granules axonal transport
- Mature = Neuophysins, carrier molecules
- Half lives = 1-3 min
Pituitary Gland: Oxytocin
Females
1) Paturition: Child birth Contractions (+) feedback
2) Milk ejection: response to suckling, contract milk ducts
3) Behavioral Effects: bonding, reduce anxiety
Males
4) Ejaculation: helps passage of sperm
5) Behavioural Effects: “
Thyroid Gland: T4, T3
++++SYNTHESIS of THYROID hormones
1. Thyroid follicles
2. Colloid has Thyroglobulin has Thyrosine
*TSH pituitary = regulator = increase!
3. I2 (iodine) + thyroglobulin = MIT / DIT
(mono/di- iodotyrosine)
4. 2 DIT = T4
5. MIT +DIT = T3
6. T4/3 split off from thyroglobulin (storage)
7. Enter blood
8. Bind to special plasma proteins
*has iodine = active transport
++++CONTROL OF THYROID HORMONE/GLAND
TRH = hypothalamic neurons (synthesis and release)
TSH = anterior pituitary –> receptors on thyroid gland
cAMP and Adenylyl cyclase ACTIVATE T4/3
T4/3 INHIBIT TRH and TSH
++++IODINE DEFICIENCY
= synthesis of thyroid hormone is deficient
= Too much FSH, not enough T4/3
= Thyroid gland = hypertrophic = Goiter = non-toxic
++++EFFECTS OF THYROID HORMONES
1) STIMULATION OF CALORIGENESIS
2) EFFECTS OF METABOLISM (basal m. rate)
3) EFFECTS ON GROWTH
4) PROMOTES ELABORRATION OF NERVOUS SYSTEM (hypothyroid child = life long complications)
5) carbohydrate up
6) lipid turnover up
7) protein metabolism
++++MOLECULAR MECHANISM
1. target cognate nuclear receptor
2. alter transcription of specific genes (proteins)
3. effects through plasma membrane and mitochondria (cannot be block by inhibitors)
4. act at plasma membrane and incrase uptake of amino acid
++++ABNORMALITIES = at birth or later
A) Hypofunction-Hypothyroidism
[1°] Myxedema
= Atrophy
= Autoimmune thyroiditis
= Goitrous Hypothyroidism / non-toxic: block synthesis of T4/3
[2°]
= Pituitary
= lack of TSH
[3°]
= hypothalamus
= lack of TRH
[Infantile]
= absence of thyroid gland
= dwarfisim and cretinism
*TREATMENT: thyroid hormones
B) Hyperfunction-Hyperthyroidism
[1°] Toxic / Goiter’s disease
= Toxic goiter due to LATS (mimic)
= Adonema or cancer: thyroid is independent of TSH
= negative feedback loop
[2°]
= pituitary tumor
= NO negative feedback
= indepenedent prodction of TSH
[3°]
= hypothalamus tumor
= NO negative feedback
= independent production of TRH
*TREATMENTS:
- Surgery
- Radioacive iodine
- Antithyroid drugs
Calcium
- Skeleton
- Blood clotting
- Transmembrane potentials
- Excitability of nervous
- Contraction of muscles
- Release hormones and neurotransmitters
In circulation
50% free 50% albumin
99% IN BONES
++++HORMONAL CONTROL
- Maintained by exchange between bones and plasma
- Intestinal absorption and kidney excretion
++++HORMONES THAT REGULATE CALCIUM
1) PTH: parathyroid gland [INCREASE]
2) Calcitonin: thyroid gland [DECREASE]
3) Vitamin D: [INCREASE]
- calcium cycle!!!
vitamin D and PTH –> plasma
Calcitonin –>bone and kidney
Parathyroid hormone
Chief cells of Parathyroids (4)
No parathyroid = PTH = No calcium = tetanic convulsion/death
++++PTH STRUCTURE
84 A-acid, N-terminal only
34 A-acid full activity
- Preproparathryroid –> Proteolytic Cleavage –> PTH
- Half life= 3-18 min
++++FUNCTIONS OF PTH
1. increase Ca absorption and Reabsorption (gut, kidney, bone)
2. Vtiamin D synthesis
++++CONTROL OF PTH
- feedback loops from circulating Ca2+
++++MECHANISM OF PTH
- Cognate receptor
++++ABNORMALITIES
A) Hypoparathyroidism
- low Ca2+
- low active Vitamin D
- convulsions
TREATMENT: active vitamin D
B) Hyperparathyroidism
- Adenoma
- kidney stones
- increase absorption
TREATMENT: ermoval of affected glands,
Vitamin D
Diet
Cholestero metabolite (not a vitamin)
++++SYNTHESIS
1. UBV light + 7-dehydrocholesterol in skin
2.. 25-hydroxylation in liver
3. 1-hydroxylation in kindney
= 1,25-dihydroxyvitamin D3
++++FUNCTIONS
- increase calcium absorption in intestin (duo and upper jejunum)
- immune
- anticancer
++++REGULATION
- low calcium = INCREASE vit. D
- high calcium = decrease vit D
LOW vitamin D
= rickets
= osteomalacia (soft bone)
= allergies
= cancer
autoimmune
vitamin D receptor VDR = regulates gene trasncription
Calcitonin
Adrenal Glands
- upper kdiney
- heavier in male
- cortex and medulla
= cortex is large-lipid / mesoderm / steroid hormones
= medulla is chromaffin Kbichromate browen granules / neural crest / catecholamine epineprhine & peptide hormones
++++ADRENAL CORTEX
Different layers of cortex produce different hormones
Faschiculata:
- Glucocorticoids (Steroid)
Glomerulosa:
- Mineralocorticoids (steroid)
- Aldosterone (has key enzymes = 18-hydroxylase)
Corticosterone
Progesterins
++++MOLECULAR MECHANISM
- regulator gene transcription
++++FUNCTIONS
1) MINERALO - ALDOSTERONE : Na+ and Cl- increase reabsorption
- OR gain Na+ & loss of K+ or a proton
- plasma concentration and pH
2) GLUCOCORTICOIDS - CORTISOL/CORTICOSTERONE
- salt retention
- protein and carbohydrtae metabolism: increase glucose levels. adrenal diabetes
- Lipid metabolism: hyperlipidemia and hypercholesterolemia
- Glucocorticoids in bone: osteoporosis (breakdown bone)
- Anti-inflammatory and immonusuppressive actions: reduce
++++CONTROL OF GLUCOCORTICOID - CORTISOL
by: ACTH, POMC, increase!
++++MECHANISM OF ACTH - ant. pituitary
- diurnal rhythm
++++STRESS RESPONSE
Addison’s disease
Hypofunction of Adrenal cortex
- destruction of gland
= due to autoimmune attack and tuberculosis
Feedback pathway
1. loss of glucocordticoid: cortisol and aldosterone
2. loss of blood sugar
3. lack of energy / muscle weakness
4. loss of mineralocorticoid
5. ions imbalance
6. loss of Na+ in plasma
7. increase of K+ in plasma
8. Acidosis due to buildup of K+
9. shock death
Treatment: add the hormones
Cushing’s disease
Hyperfunction
- elevated ACTH (adrenal or pituitary tumors)
- hyperplasia = big
-androgen, sex hormone: in women = increase masculinization
- hypetension
Feedback pathway
1. increase glucocorticoids: crotisol/aldosterone
2. increase blood sugar
3. loss of proteins: osteoporosis
4. increase mineralocorticoids
5. increase sodium retention : puffy face
6.hypertension
Treatment: removal of adrnal gland subtotal
Pancreas: insulin B, glucagon a
glucagon = raise glucose
insulin = decrease glucose
INSULIN DEFICIENCY
1. beta cells destroyed
2. diabetes mellitus
3. glucose accumulates
4. cells cant take up glucose bc no insulin for receptors
5. fatty acids = source of energy
6. if not enough fatty, = increase of acid
7. decrease pH, diabetic coma, death
8. excess glucose go urine = polyurea thirst
*anti diuretih homrone: stops peeing
Diabetes type 1
- descruction of B cells (no insulin)
- or defective insulin release (drugs)
- lack of glucose to brain = hypoglemic coma, insulin shock
Daibetes type 2
- insulin normal or HIGH
- Hyporesponsiveness / resistance of insulin by cells
- Obesity and overeating
- Excess glucose = shuts down system
