Anatomy/Phys - Endo Flashcards
Chemical Messengers
Neurotransmitters: released by axon terminals of neurons and act locally
Endocrine hormones: released by glands or specialized cells into the circulating blood and acts on target cells at another location – distant organ
Neuroendocrine hormones: secreted by neurons into the circulating blood and acts on target cells at another location
Paracrines: secreted by cells into the ECF and affect neighboring target cells other than those that secrete them– close by
Autocrines: secreted by cells into the ECF affect the same cells that secrete them
Cytokines: peptides secreted by cells into the ECF and can function as autocrines, paracrines, or endocrine hormones. (eg: interleukins, lymphokines, leptin)
Three main classes of hormones
- Proteins and polypeptides
- Hormones secreted by hypothalamus, pituitary gland, pancreas, parathyroid etc. - Amino acid tyrosine-based hormones
- Hormones secreted by thyroid and adrenal medulla – epinephrine and norepinephrine - Steroids
- Synthesized from cholesterol
- Secreted by gonads, adrenal cortex, placenta
TRANSPORT OF HORMONES
- Water- soluble hormones (peptides and catecholamines) are dissolved in the plasma and transported from their sites of synthesis to target tissues
- Lipid-soluble hormones (Steroid and thyroid hormones), circulate in the blood mainly bound to plasma proteins – globulins (nearly 99%)
Mechanisms of Hormone Action
- Water-soluble hormones (peptide hormones and biogenic amines except thyroid hormone)
- Cannot enter the target cells/cannot cross cell memrbane
- Act on plasma membrane receptors
- Coupled by G proteins to intracellular second messengers that mediate the target cell’s response
- Preformed enzymes
- Shorter amount of time than lipid soluble - Lipid-soluble hormones (steroid and thyroid hormones)
- Cross the cell membrane easily
- Act on intracellular receptors that directly activate genes
Water-Soluble Hormones
peptides and catecholamines
-Receptor: Outer surface of cell membrane
-Intracellular action: Production of second messengers, e.g., cAMP, Fast acting
-Storage: Stored in vesicles
-Plasma transport: Dissolved in plasma
(free, unbound), Exception: Insulin like growth factor
-Half-life: Short (minutes)
Lipid-Soluble Hormones
steroids, thyroid hormones
- Receptor: Inside the cell, usually in the nucleus
- Intracellular action: Stimulates the synthesis of specific new proteins, Slow acting
- Storage: Synthesized as needed, Exception: thyroid hormones
- Plasma transport:Attached to proteins that serve as carriers, Exceptions: adrenal androgens
- Half-life: Long (hrs,days)
The Pituitary Gland
- Lies in the sella turcica of the base of the skull
- Connected to the hypothalamus by the pituitary/hypophyseal stalk
- The pituitary gland (hypophysis) has two major lobes
1. Posterior pituitary lobe (neurohypophysis): - Pituicytes (glial-like supporting cells) and nerve fibers
- Extension of ectoderm that forms brain
2. Anterior pituitary lobe (adenohypophysis) - Glandular tissue
- Extension of roof of oral cavity
- Ratheke’s pouch
-Between these is a small, relatively avascular zone called the pars intermedia. Produces melanocyte stimulating hormone
Anterior Pituitary
- Originates as an out-pocketing of the oral mucosa (Rathke’s pouch*)
- Connected to the Hypothalamus by the infundibulum
- Regulated by the hypothalamus via releasing and inhibiting hormones that are transported in the hypophyseal portal system
- Five cell types can be differentiated
- Secretes six important peptide hormones
1. Somatotropes secrete: human growth hormone (GH)
2. Thyrotropes: Thyroid-stimulating hormone (TSH) or thyrotropin
3. Corticotropes: Adrenocorticotropic hormone (ACTH)
4. Gonadotropes: Follicle-stimulating hormone (FSH)
5. Gonadotropes: Luteinizing hormone (LH)
6. Lactotropes: Prolactin (PRL) - All are water soluble hormones
- TSH, ACTH, FSH, and LH are all tropic hormones (regulate the secretory action of other endocrine glands)
Growth Hormone (GH)
- Produced by somatotrophs
- Stimulates most cells, but targets bone and skeletal muscle
- Promotes protein synthesis and encourages use of fats for fuel
- Most effects are mediated indirectly by insulin-like growth factors (IGFs)
- Stimulates liver, skeletal muscle, bone, and cartilage to produce insulin-like growth factors
- Mobilizes fats, elevates blood glucose by decreasing glucose uptake and encouraging glycogen breakdown (anti-insulin effect of GH)
insulin-like growth factor
- Are tightly bound to proteins hence half- life is long (20hrs)
- Serves as a better reflection of 24hr GH secretion, than GH itself as GH is secreted in pulses and mainly at night
- Exerts its anabolic effect by increasing the synthesis of cartilage (chondrogenesis) in the epiphyseal plates of long bones; thereby increasing bone length
- Increases lean body mass, hence with aging the decrease in IGFs lead to decrease in lean body mass
Regulation of GH secretion
Stimulate Growth Hormone Secretion
- hypoglycemia
- decreased blood free fatty acdis
- exercise
- starvation or fasting, protein def
- trauma, stress, excitement
- androgens during puberty
- growth hormone-releasing hormone
Inhibit Growth Hormone Secretion
- hyperglycemia
- increased blood free fatty acids
- aging
- obesity
- growth hormone inhibitory hormone (somatostatin)
- IGFs
Thyroid-Stimulating Hormone (Thyrotropin)
- Produced by thyrotrophs of the anterior pituitary
- Stimulates the normal development and secretory activity of the thyroid
Regulation of TSH release
- Stimulated by thyrotropin-releasing hormone (TRH)
- Inhibited by rising blood levels of thyroid hormones that act on the pituitary and hypothalamus
Adrenocorticotropic Hormone (Corticotropin)
- Secreted by corticotrophs of the anterior pituitary
- Stimulates the adrenal cortex to release glucocorticoids and androgens
Regulation of ACTH release
- Triggered by hypothalamic corticotropin-releasing hormone (CRH) in a daily rhythm
- Internal and external factors such as fever, hypoglycemia, and stressors can alter the release of CRH
Gonadotropins
- Follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
- Secreted by gonadotrophs of the anterior pituitary
- FSH stimulates gamete (egg or sperm) production
- LH promotes production of gonadal hormones
- Absent from the blood in prepubertal boys and girls
Regulation of gonadotropin release
- Triggered by the gonadotropin-releasing hormone (GnRH) during and after puberty
- Suppressed by gonadal hormones (feedback)
Prolactin (PRL)
- Secreted by lactotrophs of the anterior pituitary
- Stimulates milk production
- Regulation of PRL release: Primarily controlled by prolactin-inhibiting hormone (PIH) (dopamine)
- Blood levels rise toward the end of pregnancy
- Returns to nonpregnant level few weeks post partum
- Suckling stimulates PRL release and promotes continued milk production
The Posterior Pituitary
- A downgrowth of hypothalamic neural tissue
- Neural connection to the hypothalamus (hypothalamic-hypophyseal tract)
- Nuclei of the hypothalamus synthesize the neurohormones oxytocin and antidiuretic hormone (ADH)
- Neurohormones are transported to the posterior pituitary
- Contains axons of hypothalamic neurons
- Stores antidiuretic hormone (ADH) and oxytocin
- ADH and oxytocin are released in response to nerve impulses
- Not synthesized in Pituitary
Oxytocin
- Stimulates uterine contractions during childbirth
- Also triggers milk ejection (“letdown” reflex) in women producing milk
- Plays a role in sexual arousal and orgasm in males and females
Antidiuretic Hormone (ADH)-Action
- The main target tissue is the renal collecting duct
- ADH increases the permeability of the duct to water
- Urea can pass with the water, but electrolytes cannot
ADH-Regulation of ECF volume and osmolarity
Volume Regulation:
- Stimuli arising from stretch receptors in arteries and veins chronically inhibit ADH secretion
- Decrease in blood volume causes loss of this stimuli resulting in loss of the inhibitory affect
Osmoregulation:
-Hypothalamic osmoreceptors respond to changes in the solute concentration of the blood
If solute concentration is high
- Osmoreceptors depolarize and transmit impulses to hypothalamic neurons
- ADH is synthesized and released, inhibiting urine formation
If solute concentration is low
- ADH is not released, allowing water loss
- Alcohol inhibits ADH release and causes copious urine output
Thyroid Gland
- Consists of two lateral lobes connected by a median mass called the isthmus
- Composed of follicles that produce the glycoprotein thyroglobulin
- Colloid (thyroglobulin + tyrosine + iodine) fills the lumen of the follicles and is the precursor of thyroid hormone
- Parafollicular cells produce the hormone calcitonin
Thyroid Hormone (TH)
Two Hormones:
1) T4 (thyroxine)
2) T3 (triiodothyronine)
- Major metabolic hormone
- Increases metabolic rate and heat production (calorigenic effect)
- Thyroid hormones do not act directly on many tissues but acts by being a permissive hormone, e.g.: Growth hormone functions normally only in presence of thyroid hormones.
Plays a role in
- Maintenance of blood pressure
- Regulation of tissue growth
- Development of skeletal and nervous systems
- Reproductive capabilities
Synthesis and secretion of Thyroid Hormone
1) Thyroglobulin Synthesis:
- Thyroglobulin is synthesized in the follicular cells and discharged into the follicle lumen
2) Oxidation of I– to I2 :
- Iodides (I–) are actively taken into the cell, oxidized to iodine (I2) by peroxidase enzymes, and released into the lumen
3) Iodination:
- Iodine attaches to tyrosine, mediated by peroxidase enzymes
4) Coupling:
- Iodinated tyrosines link together to form T3 and T4, mediated by peroxidase enzymes
Secretion:
- Endocytosis: Pieces of follicular colloid is endocytosed and taken back into the follicle
- Fusion: Endocytosed material fuses with lysosomes
- Proteolysis of thyroglobulin: Within the lysosomes, the thyroglobulin is cleaved into T3,T4, DI and MIT
- Secretion: T4 and T3 are secreted into the blood, the ratio usually being 20 T4 to 1 T3 (this ratio shifts toward T3 in iodine deficiency).
- Deiodination: Microsomal deiodinase removes the iodine from iodinated tyrosines (DIT and MIT). The iodine is reused for hormone synthesis.
Transport and Regulation of TH
- T4 and T3 are transported by thyroxine-binding globulins (TBGs)
- Both bind to target receptors, but T3 is ten times more active than T4
- Peripheral tissues convert T4 to T3
Negative feedback regulation of TH release
- Rising TH levels provide negative feedback inhibition on release of TSH
- Hypothalamic thyrotropin-releasing hormone (TRH) can overcomethe negative feedback during pregnancy or exposure to cold
Calcitonin
- Produced by parafollicular (C) cells
- Antagonist to parathyroid hormone (PTH)
Lowers plasma Ca2+ by-:
- Inhibiting osteoclast activity and release of Ca2+ from bone matrix
- Stimulating Ca2+ uptake and incorporation into bone matrix
- Regulated by a humoral (Ca2+ concentration in the blood) negative feedback mechanism
- No important role in humans; removal of thyroid (and its C cells) does not affect Ca2+ homeostasis
Parathyroid Glands
- Four to eight tiny glands embedded in the posterior aspect of the thyroid
- Contain oxyphil cells (function unknown) and chief cells that secrete parathyroid hormone (PTH) or parathormone
- PTH—most important hormone in Ca2+ homeostasis
Increases Blood Calcium level:
- Stimulates osteoclasts to digest bone matrix
- Enhances reabsorption of Ca2+ and secretion of phosphate by the kidneys
- Promotes activation of vitamin D (by the kidneys); increases absorption of Ca2+ by intestinal mucosa
Negative feedback control: rising Ca2+ in the blood inhibits PTH
release
Adrenal (Suprarenal) Glands
- Paired, pyramid-shaped organs atop the kidneys
- Structurally and functionally, they are two glands in one
- Adrenal cortex—three layers of glandular tissue that synthesize and secrete corticosteroids
- Adrenal medulla—nervous tissue; part of the sympathetic nervous system
Adrenal Cortex
Three layers and the corticosteroids produced
G: Zona glomerulosa—mineralocorticoids
F: Zona fasciculata—glucocorticoids
R: Zona reticularis—sex hormones, or gonadocorticoids
Mineralocorticoids
-Aldosterone is the most potent mineralocorticoid
Regulate electrolytes (primarily Na+ and K+) in ECF
- Importance of Na+: affects ECF volume, blood volume, blood pressure, levels of other ions
- Importance of K+: sets RMP* of cells
Aldosterone - Action
- Increases Na+ reabsorption by the principal cells of the late distal tubule and proximal collecting ducts of kidney
- Promotes secretion of H+ by the intercalated cells, and K+ secretion by the principal cells
- The Na+ conserving action is also seen in salivary ducts, sweat glands and the distal colon
Regulation of Aldosterone Secretion
- Renin-angiotensin mechanism: decreased blood pressure stimulates kidneys to release renin, triggers formation of angiotensin II, a potent stimulator of aldosterone release
- Plasma concentration of K+: Increased K+ directly influences the zona glomerulosa cells to release aldosterone
- ACTH: is necessary for aldosterone secretion but has little effect in controlling the rate of secretion in most physiological conditions
- Increased Na+ concentration in the ECF very slightly decreases aldosterone secretion
- Atrial natriuretic peptide (ANP): blocks renin and aldosterone secretion, to decrease blood pressure
Glucocorticoids
- Cortisol is the most significant glucocorticoid
- Released in response to ACTH, patterns of eating and activity, and stress
Cortisol-Action
- Metabolic Actions, Promotes mobilization of energy stores specifically:
- Protein: promotes degradation and increase delivery of amino acids
- Lipids: promotes lipolysis and increased delivery of free fatty acids and glycerol
- Carbohydrate: raises blood glucose, making more glucose available for nervous tissue by - Inhibiting glucose uptake in most tissues - Increasing gluconeogenesis—formation of glucose from fats and proteins in the liver
2) Permissive Actions-
- On Glucagon : promotes glycogenolysis in the liver( without cortisol fasting hypoglycemia rapidly develops)
- On Catecholamines : promotes vasoconstriction and bronchodilation( without cortisol, blood pressure decreases)
- Keeps blood sugar level relatively constant
- Maintain blood pressure by increasing the action of vasoconstrictors (catecholamines)
Gonadocorticoids (Sex Hormones)
-Most are androgens (male sex hormones) that are converted to testosterone in tissue cells or estrogens in females
May contribute to
- The onset of puberty
- The appearance of secondary sex characteristics
- Sex drive
Adrenal Medulla
-Chromaffin cells secrete epinephrine (80%) and norepinephrine (20%)
These hormones cause
- Blood glucose levels to rise
- Blood vessels to constrict
- The heart to beat faster
- Blood to be diverted to the brain, heart, and skeletal muscle
- Epinephrine stimulates metabolic activities, bronchial dilation, and blood flow to skeletal muscles and the heart
- Norepinephrine influences peripheral vasoconstriction and blood pressure
