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70 Cards in this Set

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5 Modes of Intracellular Communication
Neural, Endocrine, Neuroendocrine, Paracrine and Autocrine
3 Classes of Hormones
Peptides, Amines and Steroids
Definition of Hormone
A chemical that is produced by the body and has a specific regulatory effect on a target cell or organ
Properties of Peptide Hormones
Synthesized in rough ER. Stored in intracellular vesicles. Generally water soluble and do not require carrier proteins. Receptors are on plasma membrane of target cells. MOA is via second messengers. Usually fast onset of action but short acting responses.
Properties of Amine Hormones
Synthesized from tyrosine. Catecholamines are water soluble but thyroid hormones are not and require carrier proteins.
Properties of Steroid Hormones
Synthesized from cholesterol. Diffuse rapidly out of the cell once produced due to high lipid solubility. Generally require carrier proteins. Receptor location is intracellular. MOA is via altered gene expression. Usually slow onset of action but long lasting response.
5 Amine Hormones
Dopamine, T3, T4, Epinephrine and Norepinephrine
6 Steroid Hormones
Aldosterone, Cortisol, Testosterone, Estrogens, Progesterone and Vitamin D
Simple Negative Feedback
Occurs when a hormone or response to a hormone directly inhibits further secretion of that hormone
Complex Negative Feedback
Hormone secretion from a primary target gland that is controlled by pituitary hormones, which are in turn controlled by hypothalamic factors
Positive Feedback
The effects of the hormone result in further hormone secretion
Primary Endocrine Disorder
An excess or deficiency of secretion by the TARGET GLAND
Secondary Endocrine Disorder
An excess or deficiency of secretion by the PITUITARY GLAND
Tertiary Endocrine Disorder
An excess or deficiency of secretion by the HYPOTHALAMUS
Effect of alterations in serum protein concentration
Can effect the concentration of protein bound hormones; In hypoalbuminic states such as liver failure of nephrotic syndrome, the proportion of free calcium increases
Thyroid hormone receptors are located where?
In the nucleus
Second messenger cAMP
Is formed from ATP by the enyme adenylyl cyclase. The activity of Adenylyl cyclase depends on whether G stimulatory or inhibitory subunits are activated. cAMP activates protein kinase A and is degraded by a phosphodiesterase enzyme.
Second messengers DAG and IP3
Are produced by phospholipase C which is activated by a G protein subunit. IP3 causes the release of stored calcium in the cell and DAG in the presence of calcium activates protein kinase C
Receptor tyrosine kinases
Directly initiate phosphorylation in the cell when occupied with thier hormone
Second messenger cGMP
Guanylyl cyclase activates when hormone binds and produces cGMP from GTP. cGMP is broken down by a phosphodiesterase enzyme.
Eicosanoid second messengers
Are actually hormones themselves that are derived from arachidonic acid. This group includes prostaglandins, prostacyclins, thromboxanes and leukotrienes
Enzyme that produces arachidonic acid?
Phospholipase A2; Corticosteroids inhibit this enzyme
Enzyme that produces prostaglandins and thromboxane from arachidonic acid?
COX; NDAID's inhibit this enzyme
Enzyme that produces leukotrienes from Arachidonic acid?
LOX
MOA of steroid hormone?
Hormone diffuses into the cytoplasm and binds to receptor. Receptors dimerize and bind to DNA at a steroid response element upstream from the gene site.
What is the anterior pituitary composed of?
Epithelial cells from the oral cavity
The 6 major hormones secreted by he anterior pituitary
1. Growth hormone
2. Thyroid stimulating hormone
3. Adrenocorticotropic hormone
4. Follicle stimulating hormone
5. Lutenizing hormone
6. Prolactin
Anterior pituitary hormone release is influenced by these hypothalamic release factors
TRH
CRH
GnRH
GHRH/Somatostatin
Why is pulsatile release important to maintain hormone receptor sensitivity?
If constantly stimulated, hormone receptors will be downregulated. A clinical example would be giving an agonist in high doses; at first, there will be an excess of hormone production - but later the production would drop drastically due to receptor downregulation
2 general effects of growth hormone
1. Regulator of final body size - stimulation of linear growth occurs via insulin like growth factor I
2. Metabolic effects that oppose insulin - lipolysis in adipose tissue, reduced glucose uptake in muscle and gluconeogenesis in the liver
Secretion of most GH occurs when?
During the first 2 hours of deep sleep.
Acute stress also induces GH secretion.
What is the short term stimulus for GH secretion?
Hypoglycemia via the GI hormone ghrelin
What is the long term stimulus for GH secretion?
Starvation
GH secretion is regulated by 4 negative feedback pathways
1. GH inhibits its own secretion
2. IGF-1 inhibits GH secretion
3. IGF-1 inhibits GHRH secretion
4. IGF-1 stimulates somatostatin secretion
Most common cause of death in patients with acromegaly?
Congestive heart failure
Name the 2 hormones produced in the posterior pituitary and the nuclei where they are made
1. ADH - supraoptic nucleus
2. Oxytocin - paraventricular nucleus
How is the rate of ADH secretion regulated by osmoreceptors?
ADH secretion is most sensitive to altered extracellular osmolality, which is sensed by neuronal osmoreceptors. An increase in plasma osmolarity of just 1% is sufficient to increase ADH secretion and cause thirst and water retention at the kidney
How is the rate of ADH secretion regulated by baroreceptors?
A decrease in blood volume of more than 15% is a highly potent stimulus for ADH secretion and results in renal water conservation.
Increased blood volume stretches the heart atria, which suppresses ADH secretion .
What is another name for ADH?
Vasopressin
Which two receptors does ADH act on?
V1: causes vasocontriction in vascular smooth muscle
V2: causes water retention in the kidney
Three major function of oxytocin?
Stimulate uterine contractions, stimulate milk ejection and promote maternal behavior
Role of oxytocin in labor
Dilation of the cervix stimulates release of oxytocin. Oxytocin stimulates uterine contraction. Uterine contractions cause further cervical dilation which causes more oxytocin release. The cycle ends upon birth of the infant.
Two pharmacological uses for oxytocin
1. Induction of labor
2. Treatment of postpartum hemorrhage
List the three hormones that the adrenal cortex produces and the layer that produces them
1. Aldosterone - zona glomerulosa
2. Cortisol - zona fasciculata
3. DHEA - zona reticularis
What are the 3 major reactions that occur during steroid synthesis from cholesterol?
1. Addition of OH groups by hydroxylases
2. C-C bond cleavage by desomolase
3. Oxidation/reduction by hydroxysteroid dehydrogenase
Hydroxylase and desmolase reactions require a CYP450.
This is how it works
Structure of progesterone
(C21)
Important for:
1. menses and breast development
2. implantation of fertilized ovum
3. maintenance of pregnancy
Structure of Cortisol
(C21)
Important for:
1.mediates response to stress
2. stimlates gluconeogenesis
3. coordinates carbohydrate, fat, protein metabolism
4. anti-inflammatory properties
Structure of Aldosterone
(C21)
Important for:
1. regulates electrolyte and water balance
2. stimulates Na+ uptake and K+ excretion
3 . Raises blood pressure and fluid volume
Structure of testosterone
(C19)
Important for:
1. Stimulates spermatogenesis.
2. Secondary male sex characteristics
3. Activation of anabolic pathways (muscle and bone)
Structure of estradiol
(C19)
Important for:
1. Regulation of menstrual cycle
2. Secondary female sex characteristics
Overall pathways of steroid synthesis
What is the major source of estrogens in post-menopausal women?
DHEA
What is the major androgen released by the adrenal cortex?
DHEA
What enzyme is responsible for estrogen production?
Aromatase
What 4 steroid producing enzymes are located in the inner mitochondrial membrane?
1. 20,22-desmolase
2. 11-hydroxylase
3. 18-hydroxylase
4. 18-HSD
What steroid producing enzyme is located in the SER and the nucleus?
5-a-reductase
Describe the pathway of cortisol production starting with ACTH binding to the receptor:
ACTH binds to the receptor activating the G protein. This results in cAMP production which turns on Protein Kinase A. PKA turns on cholesterol esterase which liberates cholesterol from storage. The cholesterol enters the mitochondria through a StAR protein and exits as cortisol.
The production of aldosterone is under positive and negative control from many substances
This system uses the DAG/IP3 second messenger system for upregulation and the antagonistic effect of cGMP on cAMP for downregulation
What is StAR protein and what does it do?
StAR stands for steroidogenic acute regulatory protein.
It shuttles cholesterol in and out of the mitochondria.
What rapid effect does ACTH binding have on a cell in the adrenal gland?
Production of StAR protein
4 types of regulation in steroid synthesis
1. Acute: availability of cholesterol (enzyme or transport defect)
2. Transport by StAR (the rate limiting step in all steroid pathways!)
3. Chronic: synthesis of P450 enzymes
4. Second messenger pathways (have to be intact)
What is the rate limiting step in all steroid synthesis pathways?
Transport of cholesterol in/out of the mitochondria by StAR protein
What do DNA binding domains of steroid hormone receptors all have in common?
They all contain zinc-finger domains.
3 types of steroid hormone binding proteins
1. corticosteroid binding globulin (CBG or transcortin)
2. sex hormone binding protein (SHBP) or gonadal steroid binding globulin (GBG)
3. albumin (non-specific)
Where does inactivation of steroid hormones occur and what types of reactions are there?
In the liver.
1. Reduce double bonds in rings
2. Reduce keto groups to -OH
3. Conjugate hydroxyl groups with:
(a) Sulfate groups: Donor PAPS
(b) Glucuronic acid groups: Donor UDP-Glucuronic acid
What substance are hormones, bilirubin and other drugs conjugated with in the liver to make excretion easier?
Glucuronic acid
What pituitary hormones are made by the basophilic cells?
FSH, LH, ACTH and TSH.
(B-Flat)
What pituitary hormones are made by the acidophilic cells?
Prolactin and GH
Name the 6 hypothalamic hormones:
1. Dopamine (prolactin inhibiting factor)
2. CRH (regulates ACTH and B-endorphin)
3. TRH (regulates TSH and prolactin)
4. GnRH (regulates LH and FSH)
5. GHRH (regulates GH)
6. Somatostatin (inhibits GH and TSH secretion)