Endocrine Flashcards
Hypothalamic hormones
- PRH
- TRH
- CRH
- GHRH
- GnRH
Ant. Pituitary Hormones
- Prolactin
- TSH
- ACTH
- GH
- FSH/LH
Homeostasis is driven by what system?
Endocrine
Who came up with the term homeostasis?
Walter Cannon
Components of homeostasis
- sensory system
- integrating centre
- effector/response system
- negative feedback loop
Negative feedback loop
Mechanism by which homeostasis fluctuates around set point
Hyper-dysfunction
Too much of certain hormone
Hypo-dysfunction
Too little hormone
Resistance
Too little effect
Endocrine gland
Tissue which releases a substance into bloodstream
- substance travels via blood to target cell
4 classifications of hormones
- Polypeptides and proteins
- Amines
- Glycoproteins
- Steroids
Catecholamine
Special type of amine hormone
- synthesized in advance
- stored in secretory vesicles
- released from cell by exocytosis
- dissolved in plasma
- short half life
- epinephrine and norepinephrine for example
Glycoproteins
Consist of protein bound to one or more carbohydrate groups
- for example FSH and LH
Steroids
Derived from cholesterol after an enzyme cleaves off the side chain attached to the 5 C “D” ring
- synthesized on demand
- not stored
- released from cell by diffusion
- bound to carrier proteins in blood
- long half life
- includes testosterone, progesterone and cortisol
Autocrine
secretory cell = target cell
Paracrine
secretory cells act on other cells in the local environment
Endocrine
cell makes molecule and secretes it into blood stream to travel to target cell
Peptide
- synthesized in advance
- stored in secretory vesicle
- released from cell by exocytosis
- dissolved in plasma
- short half life
- insulin is an example
Amine (thyroid)
Hormones derived from amino acids tyrosine and tryptophan
- synthesized in advance
- stored in secretory vesicle
- released from cell by diffusion
- bound to carrier proteins in blood
- long half life
- T4 or thyroxine
Receptor binding is what?
Highly specific!
Where are receptors for most hormones found?
Plasma membrane of target cell
- hormone binds to extracellular domain and activates one or more cytoplasmic signalling pathways
Where are steroid receptors found?
Cytoplasm
Where are thyroid receptors found?
Nucleus
Adenylate cyclase pathway
- hormone goes through bloodstream and binds BETA to receptor on target cell
- G proteins on cytoplasmic side translocate to adenylate cyclase
- g-alpha protein dissociates translocates across membrane to adenylate cyclase (becomes activated)
- once AC is activated it can produce cAMP from ATP
- cAMP can signal protein kinase to become active (pulls off regulatory unit)
- Protein kinase can then go on to activate other molecules (stimulate hormonal response)
- stick phosphates on things (on/off switch)
Adrenergic receptors
Class of g-protein coupled receptors that are the targets of catecholamines (epinephrine and norepinephrine)
Beta adrenergic receptors
Activate adenylate cyclase via G(s)
Alpha adrenergic receptors
Activate phospholipase C via G(q)
Phospholipase C Pathway
- hormone goes through bloodstream and binds to ALPHA receptor on target cell
- G (alpha) proteins on cytoplasmic side dissociate
- G-protein subunit travels through plasma membrane and activates phospholipase C
- once phospholipase C is activated it can catalyze the breakdown of a particular membrane into DAG and IP3
- IP3 enters the cytoplasm and binds to receptors in the endoplasmic reticulum
- this binding causes the release of stored Ca2+
- diffuses into cytoplasm where it acts as second messenger to promote hormonal effects
Mechanism of STEROID hormone receptors
- steroid hormones are transported bound to plasma carrier proteins
- dissociate from plasma carriers and pass through membrane of target cell (lipophilic)
- hormone binds to receptors in cytoplasm
- hormone bound receptor translocates to the nucleus where it binds to DNA
- stimulates genetic transcription resulting in new mRNA synthesis
- new mRNA codes for production of new proteins
- produce hormonal effects in target cell
Mechanism of THYROID hormone receptors
- T4 (thyroxine) transported in blood bound to plasma carrier proteins
- dissociate from plasma carriers and pass through membrane of target cell (lipophilic)
- In cytoplasm T4 is converted into T3
- T3 uses binding proteins to enter the nucleus
- hormone bound receptor binds to DNA
- stimulates genetic transcription resulting in new mRNA synthesis
- new mRNA codes for production of new proteins
- produce hormonal effects in target cell
ACTH
stimulates adrenal cortex to secrete glucocorticoids (cortisol)
TSH
stimulates thyroid to produce and secrete T3 and T4 (thyroxine)
GH
stimulates movement of amino acids into cells and proteins to promote overall tissue and organ growth
FSH
stimulates growth of ovarian follicles in females and production of sperm cells in male testes
PRL
stimulates milk production by female mammary glands after giving birth and plays a role in supporting regulation of male reproductive system
LH
stimulates ovulation and conversion of ovulated ovarian follicle into corpus luteum in females and stimulates secretion of testosterone in males
Somatotropin
Another name for growth hormone
Adrenal glands
Paired organs that cap superior borders of kidney
Adrenal gland strucutre
Outer cortex made up of 3 zones - zona glomerulosa - zona fasiculata - zona reticular and an inner medulla
Zona glomerulosa secretes?
Mineralocorticoids
Zona fasiculata secretes?
Gluococorticoids
In what region of the adrenal cortex are receptors for ACTH found?
Zona fasiculata
Dominant glucocorticoid in humans? Rats?
Cortisol; corticosterone
Inner medulla secretes?
Catecholamines and epinephrine
Cortisol is essential for life. WHY?
- protects against hypoglycemia
- promotes gluconeogenesis
- plays role in immune system, bone and muscle
- natural regulator of inflammatory response
What happens when you have too much cortisol?
- breakdown of skeletal muscle for gluconeogenesis
- suppresses immune system
- breaks down bone
- affects brain function
- Cushing’s
Cushing’s syndrome
Primary result of too much corticosteroid in blood
- prolonged exposure to drugs or disease causing high levels of CRH and ACTH
Cushing’s disease
Secondary result of to much corticosteroid in blood
- pituitary tumor causing excessive production of ACTH
- ACTH levels higher than syndrome
Addison’s disease
Low levels of cortisol
Pituitary Pars Intermedia Dysfunction
Disease in horses due to impaired pituitary gland - causes increased secretion of cortisol
Thyroid gland
2 lobes just below larynx connected anteriorly by isthmus
- largest of purely endocrine glands (20 to 25 g)
Thyroid follicle
Spherical, hollow sacs consisting of follicular cells surrounding colloid fluid
Colloid
Fluid inside thyroid follicle that contains thyroglobulin
How does thyroid produce thyroid hormones - T3 and T4?
- follicles take up iodide from blood by sodium iodide transporter
- iodide secreted into colloid by pendrin transporter
- iodide is oxidized and attached to tyrosine within thyroglobulin protein (helped by TPO - removes electron so iodine has a spot to bind to)
- if one iodine attaches you get monoiodotyrosine
- if 2 iodine attach you get diiodotyrosine
- tyrosine molecules can further modify MIT and DIT structures to make T3 and thyroxine
- thyroglobulin gets taken back up by follicular cells and cut up so t3 and t4 are separate and can be secreted into blood stream
Thyroid hormone function
- regulate BMR
- needed for normal gonadal development
- needed for normal embryonic/fetal development
Hypothyroid
Low levels of thyroid hormones (T3/4)
- high TRH and TSH
- Goiter (excessive growth)
Hyperthyroid
High levels of T3/4
- low TRH and TSH
- Exophthalmos
Graves Disease
Hyperthyroid
Cretinism
Congenital deficiency of thyroid hormones usually due to hypothyroid mother
- reduced physical growth and severe mental deficiency
- treated with thyroxine soon after birth to restore symptoms
Half life of protein
Very low (6 to 20 mins) so that you don’t grow out of control
Most abundant ant. pit. hormone
Growth hormone
Growth hormone polypeptide sequence
191 AA
Liver glucose release ___ by GH and ___ by IGF1
increased; decreased
Plasma glucose concentration ___ by GH and ___ by IGF1
increased; decreased
Lipolysis in adipocytes ___ by GH and ___ by IGF1
increased; decreased
Sensitivity of tissue to insulin ___ by GH and ___ by IGF1
decreased; increased
Muscle amino acid uptake and protein synthesis ___ by GH and ___ by IGF1
increased; increased
In growing children under production of GH results in
Pituitary dwarfism
- small size, proportions
- normal shape at maturity but stunted
In growing children over production of GH results in
Pituitary gigantism
In adults under production of GH results in
Cushing’s syndrome
- GH synthesis inhibited by increased cortisol
In adults over production of GH results in
Acromegaly
- thickening of bones, joints and skin
- enlargement of internal organs
Hydroxyapatite crystals
Calcium phosphate lattice
Ca10(PO4)6(OH)2
Osteoblasts
Bone forming cells
Osteoclasts
Break down bone
Bone diameter increases when
Matrix deposits on outer surface of bone
- growth around bone
Bone length increases when
Growth occurs at epiphyseal plates
- collagen layer thickens and old cartilage calcifies
- chondrocytes degenerate
- osteoblasts invade and lay bone matrix on top of cartilage base
Chondrocytes
Columns of collagen-producing cells contained in epiphyseal plates
Intra and extracellular calcium ions are essential for what?
- Neuromuscular excitation
- blood coagulation
- hormone secretion
- enzyme activity
- fertilization
How does endocrine system control calcium levels?
- Parathyroid hormone raises plasma calcium
- Calcitriol (vit. D3) stimulates intestinal absorption of calcium
- Calcitonin lowers blood calcium levels
Parathyroid gland
Little nodules that rest on thyroid gland - cannot live without it
Parathyroid hormone
Raises blood calcium
- stimulates osteoclasts to dissolve hydroxyapatite and return bone calcium to blood
- stimulates kidney to resorb calcium (excrete less)
- stimulates kidney to produce enzyme needed to activate vitamin D which promotes better absorption of calcium from food and drink
Vitamin D activation
- UV light produces vitamin D3 from precursor 7-dehydrocholesterol
- Vitamin D3 secreted into blood and sent to liver
- liver adds hydroxyl group to C 25
- 1-alpha hydroxylase enzyme converts precursor form of vitamin D3 into active form by adding final hydroxyl group to C1
- active form of vitamin D3 travels to intestines and tells them to increase absorption
Two parts of testes
- Seminiferous tubules
2. Interstitial fluid
Seminiferous tubules
Contain sertoli cells
Sertoli Cells
- regulate sperm development
- site of spermatogenesis
- produce and release testosterone
Interstitial tissue
Contains leydig cells
Lydia cells
- produce and release testosterone
Female reproductive system is 2 cycles occurring simultaneously
- Ovarian cycle - regulated by FSH and LH
2. Uterine (menstrual) cycle - regulated by estrogen and progesterone
Initial stage:
HPG axis
- ant. pit. increases FSH and LH secretion
Ovaries
- FSH influences ovarian follicles to begin maturation
Uterus
- Day 1 of menstrual bleeding
Stage 1: Follicular phase
HPG axis - Estrogen inhibits GnRH, FSH and LH Ovaries - FSH decreasing - LH increasing Uterus - estrogen stimulates endometrial growth
Stage 2: Ovulation
LH surge stimulated by estrogen
- egg ruptures out of follicle and into fallopian tube
- corpus luteum formed from what is left behind
Stage 3: Early to mid Luteal phase
HPG axis
- Corpus luteum produces progesterone and estrogen
- negative feedback so that cycle doesn’t begin again in case there is a pregnancy
Ovaries
- corpus luteum develops and regresses
Uterus
- endometrium anticipates pregnancy
* progesterone stimulates cervical mucosa layer to thicken
Stage 4: Late luteal menstruation
HPG axis
- estrogen and progesterone decrease removing negative feedback
- FSH and LH go up
Ovaries
- corpus luteum lives 12 days and if no implantation happens it undergoes apoptosis
Uterus
- endometrium requires progesterone to slough off
- menstruation starts again at 14 days post ovulation
When does basal body temp rise in relation to ovulation?
1 day after LH peak when progesterone goes up
POMC
Parent molecule - Proopiomelanocorticotropin
* 130 AA long
ACTH from POMC
Cleaved at AA 39
13 components of melanocortin system
- 4 post translational peptide products of POMC hormone
- 5 melanocortin receptors
- 2 melanocortin antagonists
- 2 proteins that modulate melanocortin activity
- 1 opiod
What are the 4 post translational peptide products of POMC hormone?
- alpha melanocyte stimulating hormone (MSH)
- beta MSH
- gamma MSH
- ACTH
Melanocortin receptors
- go through cell membrane 7 times
- have g proteins on bottom for translocating signals
Melanocortin antagonists
- Agouti
- Agouti related protein (AGRP)
What are the two proteins that modulate melanocortinin activity modulators?
- Mahogany
- Syndecan3
alpha MSH produced in brain
inhibits food intake
alpha MSH produced in skin
acts on melanocytes
MCR found where?
- skin
- adrenal
- brain
- penis
Mutation in MC4R
Leads to early onset obesity
- brain doesn’t tell you to stop eating
Agouti mice
Overproduce Agouti protein - antagonist to alpha MSH
* competes for MC1R
Dominant gene mutation in MC1R leads to?
All black jaguars
Recessive gene mutation in MC1R?
Redheads
Alpha MSH analog
PT-141
* mid life crisis drug
