APPP 25 and 28: Endocrine System Flashcards
What is the function of the endocrine system?
governs all physiological activities in the human body – includes regulation of (in response to external changes in environment):
- the different developmental stages
- metabolism and energy utilization
- sexual reproduction
- regulation of homeostasis
- chemical reactions in cells (therefore controls functions of organs, tissues, and cells)
What structures does the endocrine system include?
all organs of the body that secrete signal-transduction molecules (hormones) that travel to the target organs through blood circulation
What is the basic structure of the endocrine system?
glands secrete hormones into the bloodstream, which are then transported to target tissues
What is the exocrine system?
system of glands producing substances that are excreted via ducts or hollow lumen
- ie. sweat, salivary, mammary, stomach/GI
What is endocrine signaling?
compounds that are produced from a regulatory organ, secreted into, and distributed by the circulation system to multiple distant organs and regulate their functions
- ie. thyroid and steroid hormones
What is autocrine signaling?
compounds that are produced and usually secreted and signal to the same cell
- ie. interleukin-1 in monocytes is secreted and binds cell surface receptors on those same monocytes
What is paracrine signaling?
substances that are produced and secreted near target tissues
- ie. clotting factors, angiogenic factors, etc.
What are the primary endocrine organs? (4)
- pituitary gland
- pineal gland
- thyroid and parathyroid glands
- adrenal gland – cortex and medulla
What other organs have endocrine cells? (4)
- hypothalamus
- gonads – ovaries and testes
- pancreas
- thymus
What are the 3 mechanisms of hormone release?
- humoral: in response to changing levels of ions or nutrients in the blood (Ca2+)
- neural: stimulation by nerves
- hormonal: stimulation received from other hormones
What are hormones?
signal transduction molecules secreted from endocrine glands that travel to the target organs through blood circulation
What are the different biochemical forms of hormones? (4)
- peptide (protein) hormones
- amino acid hormones
- hormones derived from fatty acids
- steroid hormones
What are peptide hormones?
- gene products
- cannot cross cell membrane easily due to their size – instead bind to receptors on surface of cells (GPCRs that activate G-proteins), which in turn activate enzymes inside cells
What are some examples of peptide hormones?
- oxytocin (activates GPCR)
- anti-diuretic hormone (ADH) – vasopressin (activates GPCR)
- human growth hormone (activates Jak/STAT)
- all hormones secreted by the hypothalamus, pituitary glands, digestive tract, and pancreas
- insulin
What are amino acid hormones?
- not limited by their size – may bind to cell surface receptors, as well as cross cell membrane to activate internal receptors
- synthesized enzymatically from dietary amino acids (tyrosine, tryptophan, and others)
What are some examples of amino acid hormones?
- thyroid hormones (activates nuclear hormone receptors)
- melatonin (GPCR)
- epinephrine/norepinephrine (GPCR)
What are hormones derived from fatty acids?
- lipid molecules derived from membrane arachidonic acids
- binds to and activates membrane-associated GPCR (various kinds) – essential for immune functions and response to tissue injury
What are some examples of hormones derived from fatty acids?
arachidonic-acid-derived hormones:
- prostaglandins (activates GPCR)
- leukotrienes (activates GPCR)
- thromboxanes (activates GPCR)
What are steroid hormones?
- lipid molecules derived from cholesterol
- high partition coefficient allows easy passage through the cell membrane
- bind to and activate nuclear hormone receptors – leads to transcription of target genes that carry out essential functions
What are some examples of steroid hormones?
(all ligands that bind to and activate
transcription factors)
- estrogen (estrogen receptor)
- progesterone (progesterone receptor)
- testosterone (androgen receptor)
- cortisol (glucocorticoid receptor)
How do nuclear hormone receptors work?
- steroid hormone enters cells due to their chemical properties and high partition coefficient
- find and bind to soluble hormone receptors (ligand-activated transcription factors found either in cytoplasm and move into nucleus after ligand binding, or are already found in nucleus and waiting for ligand to enter)
- receptor changes conformation, allowing the recognition and binding of specific DNA elements (hormone responsive elements) located in up to several 100’s of genes
- binding recruits transcriptional co-activator (enhance) or transcription co-repressor (reduce), leading to change in the expression of gene products
What do negative and positive feedback loops do?
control hormone levels in response to downstream signals
What happens in a negative-feedback loop?
hormone release stops in response to decrease in stimulus – return to homeostasis
example:
- stimulus (eating) raises blood-glucose levels
- pancreas releases insulin in response to elevated blood glucose
- blood glucose decreases as it is used by the body or stored in the liver
- insulin release stops as blood-glucose levels normalize
What happens in a positive-feedback loop?
as long as stimulus is present, action of hormone continues (response provides more stimulus) – not at homeostasis, external stop signal is needed
example:
- infant nursing at mother’s breast stimulates hypothalamus, which stimulates posterior pituitary
- oxytocin is released, which stimulates milk production and ejection from mammary glands
- milk release continues as long as infant continues to nurse
Where is the hypothalamus?
below the thalamus and right above the brainstem
Where is the pituitary?
at the base of the brain, and rests within a hollowed out area of the sphenoid bone called the sella turcica
- connected to hypothalamus
What does the pineal body contain?
pinealocytes
What are the functions of the pineal body? (4)
- synthesizes melatonin
- inhibits reproductive function
- protects against damage by free radical
- sets circadian rhythms (biological clock)
What are the 2 neuroendrocrine functions of the hypothalamus?
- produce hormones and release through portal vein that regulates the release of anterior pituitary hormones (hypothalamic-pituitary axis)
- produce hormones (ADH and oxytocin) that are transported to the posterior pituitary for storage and release
What is the structure of the hypothalamic-pituitary axis?
- anterior pituitary lobe contains gland cells that are controlled by specific hypothalamic peptide hormones
- regulatory patterns in the HPA are formed with both negative and positive feedback loops
What is the function of the hypothalamic-anterior pituitary axis?
- governs multiple neuroendocrine regulatory functions of the hypothalamus
- ensures that endocrine secretion is matched to the demands of a changing environment
- nervous system receives information about changes in the internal and external environment from the sense organs (feedback loop)
What is the function of oxytocin?
(activates GPCR)
- females: causes contraction of the uterus and ejection of breast milk
- males: stimulates contraction of the prostate and vas deferens during sexual arousal
What is the function of antidiuretic hormone (ADH/vasopressin)?
(activates GPCR)
- stimulates kidneys to conserve water
- vasoconstriction
What is the pituitary gland?
- pea-shaped, 1/2 inch gland
- divided into anterior lobe (75%) and posterior lobe (25%)
- posterior lobe consists of axon terminals of hypothalamic neurons – stores but does not produce any hormones
What is hormone release by the anterior pituitary controlled by?
hypothalamus
Describe the action and regulation of growth hormones.
- GH release from anterior pituitary is regulated by GHRH (+) and somatostatin (-)
- GH regulates protein synthesis, particularly in skeletal muscle
What are the direct actions of growth hormones? (2)
- stimulate fat breakdown – switch to fatty acid as energy source
- glycogen to glucose (gluconeogenesis)
What are the indirect actions of growth hormones? (2)
- through activation of insulin-like growth factors
- stimulate muscle and bone growth
What do all hypothalamic hormones activate?
GPCR
What do all anterior pituitary hormones activate?
GPCR
- except GH
Hypothalamic Hormone
Growth-Hormone-releasing Hormone (GHRH) (+)
Somatostatin (-)
- anterior pituitary hormone
- primary target organ and their hormones
- primary functions at target organ(s)
- growth hormone (GH) binding causes dimerization and JAK-STAT activation
- liver, bone, muscle, kidney, and others – IGF-1
- stimulates increase in size of muscles and bones
Hypothalamic Hormone
Thyrotropin-releasing Hormone (TRH) (+)
Somatostatin (-)
- anterior pituitary hormone
- primary target organ and their hormones
- primary functions at target organ(s)
- thyroid-stimulating hormone (TSH)
- thyroid – thyroxine, triodothyronine
- stimulates thyroid gland
Hypothalamic Hormone
Corticotropin-releasing Hormone (CRH) (+)
- anterior pituitary hormone
- primary target organ and their hormones
- primary functions at target organ(s)
- adrenocorticotropic hormone (ACTH)
- adrenal cortex – cortisol
- stimulates adrenal cortex
Hypothalamic Hormone
Gonadotropin-releasing Hormone (GnRH) (+)
- anterior pituitary hormone
- primary target organ and their hormones
- primary functions at target organ(s)
- follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
- gonads – estrogen, progesterone, testosterone
- stimulates sexual development in males and females
Hypothalamic Hormone
Dopamine (-)
- anterior pituitary hormone
- primary target organ and their hormones
- primary functions at target organ(s)
- prolactin
- breast
- stimulates milk production
Where is the thyroid gland?
near the thyroid cartilage of the larynx
What are the 2 distinct cell types of thyroid follicles?
- follicular cells
- parafollicular or C cells
What do follicular cells do?
produce thyroid hormone – such as thyroxine (T4) and triiodothyronine (T3)
What do parafollicular or C cells do?
produce calcitonin – peptide hormone that activates calcitonin receptor (GPCR)
What is the primary hormone secreted by the thyroid glands?
thyroxine (T4)
- triiodothyronine (T3) is made in much lesser made
How is triiodothyronine (T3) made?
T3 has much greater biological activity and is mostly produced at the target site through deiodination of T4
What is iodine?
an essential material for T3 and T4
- minimal dietary iodine intake is 150 ug/day in adults
How are both T4 and T3 transported?
by binding to thyroid-binding globulins (TBG) and albumin
Thyroid Hormone Signal Transduction
- thyroid hormone receptors (TR) are bound to thyroid hormone response elements (TRE or HRE), as heterodimers with the retinoid X receptor (RXR)
- in absence of T3/T4, transcription activity is repressed
- T3/T4 binding to TR promotes conformation changes and turns on transcription
What are the 2 cellular functions of thyroid hormones?
- activating genes that control energy utilization, when bound to nuclear thyroid hormone receptor (T3 or T4)
- increasing ATP production, when bound to mitochondria T3 receptor (p43)
What is the effect and mechanism of thyroid hormones on the heart?
- chronotropic and inotropic
- increased number of beta-adrenergic receptors, enhanced responses to circulating catecholamines, increased proportion of alpha-myosin heavy chain (with higher ATPase activity)
What is the effect and mechanism of thyroid hormones on adipose tissue?
- catabolic
- stimulated lipolysis
What is the effect and mechanism of thyroid hormones on mucsle?
- catabolic
- increased protein breakdown
What is the effect and mechanism of thyroid hormones on bone?
- developmental
- promote normal growth and skeletal development
What is the effect and mechanism of thyroid hormones on the nervous system?
- developmental
- promote normal brain development
What is the effect and mechanism of thyroid hormones on the gut?
- metabolic
- increased rate of carbohydrate absorption
What is the effect and mechanism of thyroid hormones on lipoprotein?
- metabolic
- formation of LDL receptors
How is thyroid hormone release regulated?
- TSH (produced by anterior pituitary) is the major regulator of thyroid hormone production
- binds to specific TSH-R (GPCR) to increase the expression of thyroid hormone biosynthesis enzymes
- increases hormone synthesis and release
- T4 exerts negative feedback on TSH release at anterior pituitary
- serum TSH levels remain the most sensitive index for measurement of thyroid function
What are the relative levels of TSH and T4 in hyperthyroidism?
- low TSH
- high T4