Biology 225 - Unit 3

Hormone

Chemical substances produced by specialized organs called endocrine glands and transported through the blood stream to other tissues where they act to elicit a specific physiological response

aldosterone

steroid hormone procuded in adrenal gland that acts as key regulator of BP and fluid balance

FSH

follicle-stimulating hormone

• produce by pituitary to manage sexual development and fertility

LH

leuteninizing hormone

• regulates reproduction

• triggers ovulation and testosterone production

GH

growth hormone

• essential for stimulating growth, cell reproduction, and regeneration in children

• in adults regulates body composition, metabolism, and muscle growth

Hasimotos disease

immune system attacks thyroid gland leading to chronic inflammation and hypothyroidism

Primary hypothyroidism

thyroid gland fails to produce sufficient T3/T4 and is usually caused by hashimotos or iodine deficiency

Thyroid tumor

usually non cancerous, highly curable through surgery or radioactive iodine bc you can live w/o thyroid

hyperthyroidism

speeds body’s metabolism, usually caused by graves disease

goiter

abnormal enlargement of the thyroid gland, usually caused by iodine deficiency, hasimotos or graves

AVP and ADH

• peptide hormone that regulates water retention, BP and urine production

• example of 1st order endocrine loop

Oxytocin

• peptide hormone that regulates uterine contraction during labor, stimulates milk let -down, and promotes social bonding

• example of 1st order endocrine loop

• example of positive feedback

TRH

thyrotropin-releasign hormone

• tripepetide

• stimulates TSH release

GnRH

gonadotropin-releasing hormone

• decapepetide

• stimulates FSH and LH release

CRH

ACTH-releasing hormone

• peptide

T4 & T3

thyroid hormones

• amines but hydrophobic

Graves disease

immune system disorder that resutls in overproduction of thyroid hormones

Hypothalamus

tells pituitary which hormones to release

• TRH

• CRH

• GnRH

• GHRH

• somatostatin

• dopamine

• ADH

• oxytocin

How do hormones communicate with so many diff cells/targets?

use bloodstream as distribution network and also use highly specific receptors on target cells to ensure precision

HAP axis

Hypothalamic -Pitutiary-Adrenal

• manages stress response, metabolism and immune
  1. hypo releases CRH
  2. pituitary to release ACTH
  3. adrenal releases cortisol

HPT axis

hypo-pituitary-thyroid

• regulates metabolism, growth, and development. negative feedback loop
  1. hypo releases TRH
  2. pituitary releases TSH
  3. thyroid release T3/T4

direct signaling

secretion or hormones into bloodstream which then act as logn distance messenger for distant target cells

transmembrane receptors

• GPCRs

• enzyme linked receptors

• ion-channel receptors

Exocrine Gland

external environment

have ducts

poorly vascularized

(salivary, mammary, mucosal)

Endocrine glands

internal environment

no ducts

highly vascularized

(pituitary, thyroid, adrenal)

Autocrine & paracrine signaling

signaling cell released chemical messenger directly to receptor

Endocrine signaling

signaling cell release chemical or neuronal messenger through circulatory system before reaching receptor

Limitations of hormone definition

• not all substances that have hormonal activity are produced from specialized tissues

• many hormones have multiple source

• Some hormone act locally without releasing into circulation

Hormones are ________ &___________

hydrophobic; hydrophillic

Pepetide/protein hormones

• hydrophilic

• bind to transmembrane receptors (transduction)

• rapid effects of target cell

peptide/protein hormone synthesis

• synthesized in rough ER often as preprohormones (cleavage)

• stored in vesicles as prohormones (cleavage)

• secreted by exocytosis (cleaved into all componentes)

Amine hormones

• Chemicals that possess amine group like ach, seratonin, meltonin

• some are true endocrin hormones, others are neurotransmitters, some both

• most are hydrophiulic, but thyroid are hydrophobic

Steroid Hormones

• Derived from cholesterol

• synthesized by smooth ER or mitochondria

Three classes of steroid hormones

1. Mineralocorticoids - electrolyte balance

2. Glucocorticoides - stress hormones

3. reproductive hormones - regulate sex-specific characteristics

Steroid Hormone features

• hydrophobic - can diffuse though plasma membrane, cant be stored in cell, must be synthesized on demand

• transported to target cell by carrier proteins

• slow effects on target cell (gene transcription)

• cortisol has rapid non-genomic effects

Hydrophilic messengers bind….

transmembrane receptors

Hydrophobic messengers bind…

intracellular receptors

Agonist binding

causes a response

Antagonist binding

does not cause a response

Ligand-receptor binding

Law of Mass Action

• formation of L-R complex causes response

• more free ligand (L) or receptors (R) will increase the response

Receptors can become saturated at high L - theres a limit

Lower kd =

higher affinity

Inactivation of ligand-receptor complex

complex must be inactivated to allow responses to changing conditions

Ligand-receptor interactions

• A ligand may bind to more than one type of receptor

  • receptor isoforms

  • expressed on different target cells

  • diff responses to the same ligand

• A single cell may have receptors for many diff ligands

Intracellular receptors

• ligand diffuses across cell membrane

• binds to receptor in cytoplasm or nucleus

• L-R complex binds to specific DNA sequences

• regulates the transcription of target genes - can make transcription factors or have effects on biochem paths

Signal amplification

amplification goes in waves like pyramid

Guanylate cyclase receptor-enzyme

1. ligand binds, changing its conformation

2. activated receptor catalyzes conversion of GTP to cGMP

3. cGMP acts as second messenger and bonds to PKG

4. activated G-kinase phosphorylates proteins on serine or threonine residues

receptor tyrosine kinase (RTK)

1. ligand binds receptor

2. receptors dimerize and autophosphorylate

3. phosphorylated receptors interact with protein kinases

4. protein kinases signal to Ras protein

5. Ras switches between the active and inactive forms

MAP-Kinase phosphorylation cascade

Ras-GTP stimulates phosphorylation of MAPKKK until only MAPK

Serine/threonine kinase receptor

1. Ligand bonds the type II TGF-beta receptor

2. bound receptor dimerizes with the type I receptor

3. type I phosphorylates the type II, activating it

4. activated receptor phosphorylates a SMAD protein

5. activated SMADs enter the nucleus and regulate gene expression

Anterior pituitary

hypothalamus synthesizes and secretes neurohormones —> hypothalamic-piuitary portal system —> anterior pituitary releases hormones

• tropic hormones - cause release of another hormone

• third-order endocrine pathway

Anterior pituitary 6 major hormones

1. growth hormone (GH)

2. Prolactin (PRL)

3. Thyroid stimulating hormone (TSH)

4. Adrenocorticotropic hormone (ACTH)

5. Luteinizing hormone (LH)

6. Follicle stimulating hormone (FSH)

IGF mediate GH actions

prolactin (PRL)

stimulates milk synthesis and important for promoting maternal behavior. found in vertebrate even without mamary glands

Other PRL actions (6)

1. osmoregulation - most primative action. in fishes it is freshwater adapting hormone. amniotic fluid of mamals its for embryonic osmoregulation

2. reproduction - concerned with consequneces fo reproduction like development of mamary gland

3. development - for tadpole growth

4. metabolism - affects lipid and glucogen metabolism

5. integument - (skin) affects on hair growth, sebaceous glands, feather pattern in birds, pigmentation

6. behavioral effects - meternal behavior

TSH

controls secretion of thyroxine by the thyriod gland

ACTH

regulates the secretion of corticosteriods by the adrenal cortex. part of the stress response system

anterior pitutary hormones

1. GH

2. PRL

3. TSH

posterior pituitary hormones

1. Oxytocin

2. AVP/vassopressin/ADH

pancreas

exocrine gland - produces pancreatic enzymes and sodium bicarbonate

endocrine gland - produces insulin and glucagon

insulin - lowers blood glucose level under hyperglycemia

glucagon - raises blood glucose levels under hypoglycemia

Alpha cell

produces insulin

Beta cell

glucagon production

Islet of langerhans cells

alpha and beta cells

Insulin

• anabolic

• regulates the metabolism of carbs, fats and proteins

• Promotes the absirption of glucose from the blood

• promotes glyogenesis and lipogenesis

• triggered by high blood glucose

glucagon

• catabolic

• regulates metabolism of carbs

• promotes glycogenolysis, lipolysis, gluconeogenesis

• triggered by low blood glucose

Somatostatin

• D cells

• Major inhibitory hormone. Inhibits -

  • GH

  • TSH

  • Adenylyl cyclase

  • prolactin

  • release of insulin and glucagon

  • suppresses the exocrine secretions of the pancreas

Gastrin

triggeres stomach cells to produce HCl

Vasoactive intestinal peptide (VIP)

stimulates the intestine to release water and salts back into the intestinal tract

Additivity

when two or more hormones work in the same way on the same target

Synergism

When two or more hormones work together to increase target cell response much more than expected by additivity

Type 1 Diabetes

endocrine effect:

• loss of beta cells in pancreas

• little or no insulin produced

cuased by

• gentics

• pancreatic radiation or removal of pancreas

• toxins that damage islets

T1 Diabetes consequences

• whole body affected

• hypo and hyper glycemia

• chronic vascular diseases

T1 diabetes treatment

• control of diet and exercise

• insulin replacement

• new insulin agonists

• pancrease transplant

T2 Diabetes

• caused by insulin reisitence

• deficiency in response of pancreatic beta cells to glucose

T2 diabetes charecteristics

• insensitive to endogenous insulin

• correlates with excess abdominal fat

• inflated fat cells and over-nourished liver/muscle cells

• proliferation of pancretic beta cells

Complications of T2 Diabetes

• heart disease

• stroke

• kidney disease

• eye problems

• diabetic neuropothy and nerve damage, especially in feet

• depression

Stress Response

• hypothalamus secretes corticotropin-releasing hormone (CRH)

• anterior pituitary secreates ACTH

• Adrenal cortex secretes cortisol and stimulates target cells to increase blood glucose level

• they all go back and negative feedback eachother

Adrenal gland

1. medulla - produces catecholamines like epi and norepi

2. cortex - corticosteroids like glucocorticoids (cortisol), mineralcorticoids, and adrogens

Effects of cortisol

1. proteins and fats broken down and converted to glucose, leading to increased blood glucose

2. possible suppression of immune system

Addison’s Disease

• primary adrenocortical insufficiency

• mosyly autoimmune

• results in weakness, weight loss, nausea, hypotension, hypoglycemia

• associated with high ACTH (loss of neg feedback)

• get hyperpigmentation bc melanin production no longer inhibited

Cushings disease

• hypercortisol

• can occur from adrenal of pituitary abnormalities

• ACTCH independent or dependent

• symptoms - obestiy, skin changes, increase hair, hypertension, gonadal dysfunction, psycological disorders, muscle weakness

Short term stress response

effects of epi and norepi

• glycogen break down to glucose so increase blood sugar

• increased BP

• increated breathing rate

• increased metabolic rate

• change in blood flow patterns, leadign to increase alertness and decreased digestibe, excretory, and reproductive system activity

Isoreceptor

bind same hormone but are diff proteins

epi binds:

• beta -1 receptor- glycogen breaks down and glucose released

• beta 2 receptor - vessel dialates

• alpha receptor - vessel constricts

In marine environments…

animals tend to gain salt, lose water

in freshwater

animals lose salts and gain water

in terrestrial environments

animals tend to lose water

Osmoconformer

internal and external osmolarity similar

Osmoregulator

osmolarity constant regardless of external environment

Ionoconformer

exert little control over ion profile within extracellular space

• exclusivly in marien animals

ionoregulator

control ion profile of extracellular space

Stenohaline

can tolerate only narrow range of external salinities

Euryhaline

can tolerate wide range of external salinities

Euryhaline osmoconformer

allows osmolarity to decrease in parallel with water until death

Stenohaline osmoconformer

dies ager very modest osmotic disruption

Euryhaline osmoregulator

defends a nearly constant internal state but eventually succumbs

stenohaline osmoregulator

can defend its internal osmolarity over a narrow range of external osmolarities

Four features of transport epithelia

1. asymetrical distribution of membrane transporters - solutes selectivly transported across membrane

2. cells interconnected to form impermeable sheet of tissue - little leakage between cells

3. High cell diversity within tissue

4. abundant mitochondria - large ATP supply

Transcellular transport

tight epithelia can transfer solutes across the cell using transporters on the apical and basolateral plasma membrane

Paracellular transport

In elaky epithelia, small solutes can also move between cells, passing through the tight junctions that interconnect cells

Osmoregulation in saltwater fish

• gain of water and salt ions from food and water

• excretion of salt from gills

• excretion sof salt and some water in urine

• osmotic water loss though gills and body surface

Osmoregulation in freshwater fish

• uptake of water and some ions in food

• uptake of salt in gills

• osmotic water gain though gills and other body surfaces

• excretion of large amounts of water in urine