Lecture Endocrine System Part I
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What is the endocrine system? What are the Endocrine glands? what other tissues are involved?
the body's second great controlling system which influences metabolic activities of cells by means of hormones
pituitary, thyroid, parathyroid, adrenal, pineal, and thymus
The pancreas and goands
produce both hormones and exocrine products
has both neural functions and releases hormones (neuroendocrine organ)
- Other tissues and organs that produce hormones:
- -adipose cells
- -pockets of cells in the walls of the small intestine
What are autocrines and paracrines?
autocrines: checmicals that exert effects on the same cells that secrete them
paracrines: locally acting chemicals that affect cells other than those that secrete them
*these are not considered hormones since hormones are long-distance chemical signals
What is a hormone and what are its basic functions?
- chemical substances secreted by cells into the extracellular fluids
- -regulate the metabolic function of other cells
- -have lag times ranging from seconds to hours
- -tend to have prolonged effects
- are classified into:
- 1. Acid Based Hormones
- 2. Steroid hormones
biologically active lipids with local hormone-like activity
What are the three types of hormones?
1. Amino Acid Based: Amines, thyroxine, peptide, and protein hormones
2. Steroids: gonadal and adenocortical hormones (sythesized from cholesterol)
3. Eicosanoids: leulotrienes and prostaglandins that are released by nearly all cell membranes (Act as autocrines or paracrines and are not true hormones)
How do hormones alter target cell activity?
By one of 2 mechanisms:
- 1. Second Messengers: (Water soluable hormones)
- -regulatory G proteins
- -amino acid-based hormones (Except thyroid hormone)
- 2. Direct gene activation (lipid soluable hormones)
- -steroid hormones
- -thyroid hormones
the precise response depends on the type of target cell
What cellular changes do hormones produce in the target cells?
Alter plasma membrane permeability or membrane potential by opening or closing ion channels
stimulate protein synthesis or regulatory molecules like enzymes
activate or deactivate enzyme systems
induce secretory activity
Describe Amino-acid based hormone action:
cAMP Second Messenger
1. Hormone (first messenger) binds to its receptor, which then binds to a G protein
2. G protein is then activated as it binds to GTP, displacing GDP
3. Activated G protein activates the effector enzyme adenylate cyclase
4. Adenylate cyclase generates cAMP (second messenger) from ATP
5. cAMP activates protein kinases, which then causes cellular effects
- *this is a positive feedback cycle with a huge amplification effect
Describe the Amino Acid-based Hormone Action:
1. Hormones binds to the receptors and activates G protein
2. G protein binds and activates phospholipase C
3. Phospoholipase splits the phospholipid PIP2
into diacylglycerol (DAG) and IP3
(both act as second messengaers)
4. DAG activates protein kinases; IP3
triggers release of Ca2+
- 5. Ca2+ (third messenger) alters cellular responses (as it binds to calmodium)
How do steroid hormones work?
hormone receptor binds to a region of DNA specific for it
this interaction prompts DNA transcription to produce mRNA
the mRNA is translated into proteins, which bring about a cellular effect
1. The steroid hormone diffuses throught eh plasma membrae and binds an intracellular receptor
2. The receptor hormone complex enters the nucleus
3. the receptor-hormone complex binds a hormone reponse element (specifis DNA sequence)
4. Binding initiates transcription of the gene to mRNA
- 5. The mRNA directs protein synthesis
What is target cell specificity?
hormones circulate to all tissues but only activate cells referred to as target cells
target cells must have specific receptors to which the hormone binds
these receptors may be intracellular ot located on the plasma membrane
- Examples of hormone activity:
- -ACTH receptors are only found on certain cells of the adrenal cortex
- -Thyroxin receptors are found on nearly all cells of the body
Describe target Cell Activation
It depends on 3 factors
- 1. Blood levels of the hormone
- 2. relatice number of receptors on the target cell
- 3. Affinity of those receptors for the hormone
target cells form more receptors in response to the hormone
target cells lose receptors in response to the hormone
How do hormones circulate in the blood? How are they removed?
- Hormones circulate in the blood in two forms- free or bound to a protein carrier
- *steroids and thyroid hormones are attached to plasma proteins
- *all other are unencumbered
- Concentrations of ciruclating hormone reflect:
- -the rate of release
- -speed of inactivation and removal from the body
- Hormones are removed from the blood by:
- -degrading enzymes
- -the kidneys
- -liver enzyme systems
How do hormones interact at target cells?
- Three types of hormone interaction:
- 1. Permissiveness- one hormone cannot exert its effects without another hormone being present
more than one hormone produces the same effects on a target cell
one or more hormones opposes the action of another hormone
How are blood levels of hormones controlled?
By negative feedback systems tha vary only within anarrow desirable range
- hormones are synthesized and released in reponse to:
- -humoral stimuli
- -neural stimuli
- -hormonal stimuli
What are humoral stimuli?
humoral stimuli: secretion of hormones in direct response to changing blood levels of ions and nutrients (simplest endocrine control)
- Example: concentration of calcium ions in the blood is monitored by the parathyroid glands
- -declining blood calcium concentration stimulated the parathyroid glands to secrete PTH (parathyroid hormone)
- -PTH causes calium centratiosn to rise and the stimulus is removed
What are neural stimuli?
neural stimuli: nerve fibers stimulate hormone release
- preganglionic sympathetic nervous system fibers stimulate the adrenal medulla to secrete catecholamines
What are hormonal stimuli?
This feedback loop is at the core of endocrinology!
release of hormones in response to hormones produced by other endocrine glands
- -the hypothalamic hormones stimulate the anterior pituitary
- -in turn, pituitary hormones stimulate targets to secrete still more hormones
Describe the Pituitary gland (hypophysis)
- Its a 2 lobed organ that secretes 9 major hormones
- It sits on the infundibulum and is connected to the hypothalamus
- Neurohypophysis: posterior lobe (neural tissue) and the infundibulum
- -receives, stores, and releases hormones from the hypothalamus
- Adenohypophysis: anterior lobe, made up of glandular tissue
- -synthesizes and secretes a number of hormones
What is the pituitary-hypothalamic relationship for the posterior lobe? (neurohypophysis)
The posterior love is a downgrowth of the hypothalamic neural tissue and is actually a part of the brain
has a neural connection with the hypothalamus
nuclei of the hypothalamus synthesize oxytocin (from paraventricular neurons) and antidiueretic hormone (ADH) (from supraoptic neurons)
these hormones are transported to the posterior pituitary to be transported throughout the body
What is the pituitary-hypothalamic relationship for the anterior lobe? (adenohypophysis)
The anterior love of the pituitary is an outpocked of the oral mucosa (ranthke's patch)
there is no direct neural contact with teh hypothalamus
- There is a vascular connection to the hypothalamus- the hypophyseal portal system:
- -the primary capillary plexus
- -the hypophyseal portal veins
- -the secondary capillary plexus
- *these act in hormone regulation
What are the adenophypophyseal hormones?
- 6 hormones of the adenohypohysis:
- GH (growth hormone)
- TSH (thyroid-stimulating hormone)
- ACTH (adrenocortical hormone)
- FSH (follicle stimulation hormone)
- LH (luteinizing hormone)
- PRL (prolactin)
- *these regulate the activity of other endocrine glands
- Also, a pro-hormone called pro-opiomelanocortin (POMC)
- -is split into ACTH, opiates, and MSH which is a CNS neurotransmitter involved in appetite
How is the hypothalamus involved in the activity of the hormones released by the anterior pituitary?
the hypothalamus sends a chemcical stimulus to the anterior pituitary
-releaseing hormones stimulate the synthesis and release of hormones
-inhibiting hormones shut off the synthesis and release of hormones
What are the tropic hormones relased by teh anterior pituitary?
Tropic hormones regulate the secretory action of other endocrine glands
TSH, ACTH, FSH, LH
What is Growth Hormone? What regulates it? What is its metabolic action?
- It is produced by somatropic cells of the anterior pituitary lobe that:
- -stimulate most cells, but targets bone and skeletal muscle
- -promotes protein synthesis and encourage the use of fats for fuel (a tissue building hormone)
most effects are mediated indirectly by somatomedinds and IGFs
- Antagonistic hypothalamic hormones regulate GH
- -growth hormone-releasing hormone (GHRH) stimulates GH release
- -growth hormone-ihibiting hormone (GHIH) inhibits GH release
- Metabolic action:
- -GH stimulates the liver, skeletal muscle, bone, and cartilage to produce insulin-like growth factors
- -direct action promotes lipolysis and inhibits glucose uptake
What is TSH?
Thyroid Stimulating Hormone (thyrotropin)
stimulates the normal development and secretory activity of the thyroid
triggered by hypothalamic peptide thryotropin-releasing hormone (TRH)
rising blood levels of thyroid hormones act on the pituitary and hypothalamus to block the release of TSH
What is ACTH?
Adrenocorticotropic Hormone (corticotropin)
stimulates the adrenal cortex to release corticosteroids that help the body resist stressors
triggered byt he hypothalamic corticotropin-releasing hormone (CRH) in a daily rythm
internal and external factors such as fever, hypoglycemia, and stressors ca trigger the release of CRH
What are gonadtropins?
Gonadotropins: follicle stimulating hormone (FSH) and luteinizing hormone (LH)
regulate the function fo the ovaries and the tested
FSH stimulates the gamete production (Egg or sperm)
absent from the blood in prepubertal boys and girls
triggered by the hypothalamic gonadotropin-releasing hormone (GRH) during and after puberty
- In females:
- -LH works with FSH to cause the mturation of the ovarian follicle
- -LH also works along to trigger ovulation
- -LH promotes synthesis and release of estrogens and progesterone
- In Males:
- -LH stimulates interstitial cells of the testes to produce testosterone
- -LH is also referred to as interstitial cell stimulating hormone (ICSH)
What is prolactin?
Protein hormone structualy similar to GH produced by lactotrophs
in females, it stimulates milk production in the breasts
i is triggered by the hyothalamic prolactic releasing hormone(PRH) and is inhibited by the prolactic inhibiting hormone (PIH)
blood levels rise toward the end of pregnancy
suckling stimulates PRH release and encourages continued milk production
What hormones does the posterior pituitary have?
Gets it from the hypothalamus!
Posterior pituitary: made of axons of hypothalamic neurons, stores antidiuretuc hormone (ADH) and oxytocin
ADH and oxytocin are synthesized in the hypothalamus
- ADH influences water balance and keeps the osmotic pressure
- -prevents urine formation
- -osmorecptors monite solute concentration in the blood
- -alcohol inhibits ADH release causing copious urine output
- oxytocin stimulates smooth muscle contractions in breasts and uterus as a positive feedback cycle ending in birth
- -plays a role in sexual arousal and satisfaction in both males and nonlactating females
Both ADH and oxytocin use PIP-calcium second messenger mechanism
*ADH deficiency results in diabetes insipidus
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