BIO2305
Endocrine System
Brief Review of Endocrine vs Nervous System
Nervous system performs short term crisis management
Controls and coordinates bodily activities that require rapid responses
Endocrine system regulates long term ongoing metabolic activity management
Endocrine communication is carried out by endocrine cells that release hormones in order to
alter metabolic activities
Endocrine System Functions
“Endo-” = within
“-crine” = to secrete (Greek)
Endocrine System - the system of glands, each of
which secretes a type of hormone directly into the
bloodstream to regulate the body
Endocrine System functions include:
Maintenance of an optimum biochemical
environment within the body
Influences metabolic activities
Integration and regulation of growth and
development
Control, maintenance, and instigation of
sexual reproduction
Endocrine System: Overview
Endocrine glands:
hypothalamus
pituitary (adenohypophysis)
pineal
thyroid
parathyroid
thymus
adrenal
pancreas
gonads
The hypothalamus has both neural and endocrine
functions
The pancreas and gonads produce both hormones and exocrine products
Other tissues and organs that produce hormones – adipose cells, cells of the small intestine,
stomach, kidneys, and heart
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The Endocrine System
Hormones
“Hormone” = from Greek hormao = to excite, arouse, spur
Hormones – chemicals secreted by cells into the bloodstream for transport to distant target tissues
Regulate the metabolic function of other cells
Have lag times ranging from seconds to hours
Tend to have prolonged effects
Produce effects at very low concentrations
Are classified as amino acid-based hormones, or steroids
Ultimate Goal: to generate a cellular response, regardless of method
Cellular Response - binding of chemical signals (ie: hormones) to their corresponding
receptors to induce events within the cell that ultimately change its behavior
Mechanism of Hormone Action
Hormones produce one or more of the following cellular changes in target cells:
Alter plasma membrane permeability
Stimulate gene activation & protein synthesis
Activate or deactivate enzyme systems
Induce secretory activity
Stimulate mitosis & cytokinesis
Free vs Bound Hormones:
Most endocrine systems monitor [free hormone] only
Increasing binding proteins in blood (carrier proteins, eg: T4-binding globulin or albumin),
lowers certain hormones’ effective circulating concentration
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Hormones Are Ligands
Ligand – in biochemistry, anything that binds to a protein receptor
Examples:
Ions
Hormones
Neurotransmitters
Drugs
Toxins
Gases
Receptor – a cellular protein that binds to a ligand; used to continually monitor changes in the internal
or external environment
Types:
Membrane Receptor – embedded in the membrane, with receptor site facing outward
G-protein
Ligand gated channel
Cytosolic Receptor – located within the cell’s cytoplasm
Nuclear Receptor – located within the cell’s nucleus
Classification of Hormones based on chemical composition
Hormones can be classified based on chemical composition:
Amino Acid Derivatives
Tyrosine Based – Catecholamines (Epi, NE, Dopa) & Thyroid hormones
Tryptophan Based – Serotonin & Melatonin
Protein Derivatives (most hormones belong to this class)
Glycoproteins – carbohydrate + protein
Short Polypeptides – less than 200 amino acids
Lipid Derivatives
Steroids – gonadal and adrenocortical hormones
Eicosanoids – lipid based hormones that act locally on the same cell that released it or
nearby cells (autocrine and paracrine mediators)
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Classification of Hormones
Hormone Action
Amino Acid Derivatives
Tyrosine Based
Catecholamines
Bind to membrane receptors
Activate 2nd messenger systems
Thyroid Hormones
Diffuse through membrane
Activate genes for protein synthesis
Tryptophan Based
Serotonin, Melatonin
Bind to membrane receptors
Activate both ligand-gated ion channels and G protein-coupled receptors
Protein Derivatives
Glycoproteins & Short Polypeptides
Diffuse through membrane
Activate genes for protein synthesis and activate existing proteins
Lipid Derivatives
Steroids & Eicosanoids
Bind to membrane receptors or diffuse through membrane
Activate 2nd messenger systems and genes for protein synthesis
*Remember, just because a substance is lipophilic does not necessarily mean all
receptors are intracellular; some are membrane-bound*
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Classification of Hormones based on receptors
Hormones can also be classified based on location of receptors:
Membrane Receptors
Second messengers systems (G protein-linked)
Tyrosine kinase-linked receptors
Hormone-gated ion channels
Intracellular and intranuclear receptors
Most amino acid based-hormones use G protein-linked receptors for signal transduction
Most steroid hormones can diffuse through the membrane and, therefore, bind to receptors found
in the cytosol and nucleus, with the goal of activating or repressing genes
AA-Based Hormone Action: cAMP-2nd Messenger
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AA-Based Hormone Action: PIP2-Calcium
G Proteins and Hormone Activity
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Steroid Hormones
Steroid hormones diffuse into target cells to bind and activate
a specific intracellular receptor
Cytosolic hormone-receptor complex (Type I NR)
travels to the nucleus
binds to a DNA-associated receptor protein
prompts DNA transcription & protein synthesis
Nuclear hormone-receptor complex (Type II NR)
located within nucleus at DNA-associated
receptor protein
prompts DNA transcription & protein synthesis
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Steroid Hormones
Target Cell Specificity
Hormones circulate to all tissues but only activate target cells
Target cells must have specific receptors to which the hormone binds
These receptors may be intracellular or 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
Target Cell Activation
Target cell activation depends on three factors
Blood levels of the hormone
Relative number of receptors on the target cell
The affinity of those receptors for the hormone
Up-regulation – target cells form more receptors in response to the hormone
Down-regulation – target cells lose receptors in response to the hormone
Hormone Concentrations in the Blood
Hormones circulate in the blood in two forms – free or bound
Hormones bound to plasma proteins:
Steroids (corticoids)
T3 T4
GH
oxytocin & vasopressin
Almost all others are unencumbered
Concentrations of circulating hormone reflect:
Rate of release
Speed of inactivation and removal from the body
Hormones are removed from the blood by:
Degrading enzymes
Kidney filtration
Liver enzymes
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Interaction of Hormones
Three types of hormone interaction
Permissiveness – one hormone cannot exert its effects without another hormone being present
Synergism – more than one hormone produces the same effects on a target cell
Antagonism – one or more hormones opposes the action of another hormone
Control of Hormone Release
Blood levels of hormones:
Are controlled by negative feedback systems
Vary only within a narrow desirable range
Hormones are synthesized and released in response to humoral, hormonal, and neural stimuli
Humoral Stimuli
Hormone secretion initiated by Humoral Stimuli
Humoral = of body fluids (ie: blood)
Secretion of hormones in direct response to changing blood levels of ions, nutrients, and gases
Example: [Ca2+] in the blood
↓ [Ca2+] in blood stimulates parathyroid glands to secrete PTH (parathyroid hormone)
↑ PTH causes [Ca2+] in blood to rise (Ca2+ is reabsorbed in kidneys and leached from bones)
and the stimulus is removed
Hormonal Stimuli
Hormone secretion initiated by Hormonal Stimuli
Hormones are released in response to hormones produced by other endocrine organs
Hypothalamic “releasing-hormones” stimulate the anterior pituitary to release hormones
Anterior pituitary’s tropic hormones stimulate target glands to secrete still more hormones
Tropic vs. Trophic:
Tropic – describing a hormone that stimulates release of another hormone
Trophic – describing a hormone that stimulates growth and nourishment of a gland
(increasing hormone release by that gland)
ACTH is tropic and trophic. It causes release of cortisol from the adrenal gland (tropic),
and stimulates the growth of the adrenal gland (trophic)
Neural Stimuli
Hormone secretion initiated by Neural Stimuli
Hormones are released in response to neural stimulation originating from the CNS (brain, spinal
cord)
Action potential travels along sympathetic nerve fibers that synapse at the adrenal medulla
Chromaffin cells respond by releasing hormones (catecholamines such as EPI and NE) into
the blood.
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Endocrine Control: Three Levels of Integration
Hypothalamic stimulation from CNS
Pituitary stimulation from hypothalamic tropic hormones
Endocrine gland stimulation–from pituitary tropic hormones
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Feedback Control of Endocrine Secretion
Hormonal NFbL - Hypothalamic-Pituitary-Thyroid axis (HPT Axis)
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Hormonal NFbL - Hypothalamic-Pituitary-Adrenal axis (HPA Axis)
Neural Stimulation
ANS efferent nerve fibers stimulate hormone release
The preganglionic fiber from the CNS passes through, but
does not synapse at, the sympathetic chain ganglion. It
continues to the adrenal medulla where it synapses with
medullary glandular cells
The preganglionic sympathetic nerve fibers stimulate the
chromaffin cells within the adrenal medulla to secrete
catecholamines (Epi, NE) into the bloodstream
Chromaffin cells – modified postganglionic sympathetic
neurons within the adrenal medulla that secrete epinephrine
and norepinephrine
Chromaffin cells use the enzyme dopamine βhydroxylase to convert of dopamine to noradrenalie
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Nervous System Modulation
The nervous system modifies the stimulation of endocrine glands
and their negative feedback mechanisms
The nervous system can override normal endocrine controls
Example: Neural control of blood glucose levels (BGL)
BGL normally maintained by endocrine system
However, under stress, the body needs more glucose
The hypothalamus and the sympathetic nervous system
are overridden by cerebral cortex and limbic system to
supply ample glucose
How?
Cerebral cortex and limbic system stimulate
hypothalamus to release CRH
Adenohypophysis releases ACTH into blood
Adrenal cortex releases Cortisol
Cortisol stimulates gluconeogenesis
↑ Blood glucose level (BGL)
Overview of Major Endocrine Organs and Hormones
Hypothalamus
Thyrotropin-releasing hormone (TRH)
Prolactin Inhibiting Hormone/Dopamine (PIH)
Growth hormone-releasing hormone (GHRH)
Growth hormone-inhibiting
hormone/Somatostatin (GHIH)
Corticotropin-releasing hormone (CRH)
Gonadotropin-releasing hormone (GnRH)
Neurohypophysis
(synthesized by Hypothalamus)
Oxytocin
Vasopressin (ADH)
Adenohypophysis
Thyroid-stimulating hormone (TSH)
Prolactin (PRL)
Growth hormone (GH)
Adrenocorticotropic hormone (ACTH)
Follicle-stimulating hormone (FSH)
Luteinizing hormone (LH)
Infundibulum
Melanocyte–stimulating hormones (MSHs)
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Major Endocrine Organs
The hypothalamus sends releasing hormones to the adenohypophysis and neural stimuli to the
neurohypophysis
Hypothalamus >> Adenohypohysis:
Thyrotropin releasing hormone (TRH) >> release of TSH and PRL
Prolactin inhibiting hormone (PIH) >> inhibits release of PRL
Growth hormone-releasing hormone (GHRH) >> release of GH
Growth hormone-inhibiting hormone (GHIH) >> inhibits release of GH
Corticotropin releasing hormone (CRH) >> release of ACTH
Gonadotropin releasing hormone (GnRH) >> release of FSH and LH
Hypothalamus >> Neurohypophysis
Action potential >> ADH
Action potential >> Oxytocin
Pituitary gland – bilobed organ that secretes
nine major hormones, all use cAMP 2nd messenger system
Neurohypophysis
posterior lobe, made up of neural tissue
receives, stores, and releases hormones from the hypothalamus
Adenohypophysis
anterior lobe, made up of glandular tissue
synthesizes and secretes a number of hormones
Infundibulum
the pituitary stalk connecting the hypothalamus to the neurohypophysis
synthesizes and releases Melanocyte–stimulating hormones (MSHs)
which stimulate production and release of melanin by melanocytes in skin and hair
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Hypophysis (Pituitary Gland)
Pituitary Gland – bilobed organ that secretes nine major hormones, all use cAMP 2nd messenger
system
Neurohypophysis stores and releases two hormones from hypothalamus
Oxytocin and antidiuretic hormone (ADH)
These hormones are transported in vesicles from hypothalamus to the neurohypophysis for
release
Adenohypophysis synthesizes and releases six hormones:
Are abbreviated as TSH, PRL, GH, ACTH, FSH, and LH
Regulate the activity of other endocrine glands
Anterior Lobe of the Pituitary Gland (Adenohypophysis)
Adenohypophysis - anterior lobe of pituitary gland
made of glandular tissue
synthesizes and secretes six hormones
Six Hormones of the Adenohypophysis:
Thyroid-stimulating hormone (TSH)
Prolactin (PH or PRL)
Growth hormone (GH)
Adrenocorticotropic hormone (ACTH)
Follicle-stimulating hormone (FSH)
Luteinizing hormone (LH)
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Growth Hormone (GH)
Produced by somatotropic cells of the anterior lobe
Function:
GH stimulates liver, skeletal muscle, bone, and cartilage
to release insulin-like growth factors (IGFs)
GH increases cell metabolism and blood glucose
level
Promotes use of fats for fuel (lipolysis &
gluconeogenesis) and protein synthesis
Most effects are mediated indirectly by somatomedins
Hypothalamic hormones regulate GH
Growth hormone–releasing hormone (GHRH) stimulates
GH release
Growth hormone–inhibiting hormone (GHIH) inhibits GH
release
Metabolic Action of Growth Hormone
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Thyroid Stimulating Hormone (TSH)
Tropic hormone that stimulates the normal development and secretory activity of the thyroid gland
Triggered by hypothalamic peptide thyrotropin-releasing hormone (TRH)
Rising blood levels of thyroid hormones act on the pituitary and hypothalamus to block the release of
TSH
Adrenocorticotropic Hormone (ACTH)
Stimulates the adrenal cortex to release corticosteroids
Triggered by hypothalamic corticotropin-releasing hormone (CRH) in a daily rhythm
Internal and external factors such as fever, hypoglycemia, and stressors can trigger the release of CRH
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Gonadotropins - FSH, LH
Gonadotropin Functions:
Regulate the function of the ovaries and testes
Triggered by the hypothalamic gonadotropin-releasing hormone (GnRH) during and after
puberty
Two Gonadotropins:
Follicle-stimulating hormone (FSH)
FSH stimulates gamete (egg or sperm) production
Luteinizing hormone (LH)
LH In females:
LH works with FSH to cause maturation of the ovarian follicle
LH works alone to trigger ovulation (expulsion of the egg from the follicle)
LH promotes synthesis and release of estrogens and progesterone
LH in males:
LH stimulates interstitial cells of the testes to produce testosterone
LH is also referred to as interstitial cell-stimulating hormone (ICSH)
Prolactin
In females, stimulates milk production by the breasts
Triggered by the hypothalamic prolactin-releasing hormone (PRH)
Inhibited by prolactin-inhibiting hormone (PIH)
Blood levels rise toward the end of pregnancy
Suckling stimulates PRH release and encourages continued milk production
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Neurohormones: secreted into the blood by neurons
Neurocrine – any molecules secreted by a
neuron
Neurohormone – a neurocrine hormone
that is produced and secreted by a neuron
into the blood, targeting distant cells (ie:
ADH, oxytocin)
Contrast Neurohormones with other
Neurocrines:
Neuromodulator – slow acting paracrine
chemicals that alter the response of a
neuron more slowly than nerotransmitters;
usually found in circulating in CSF
Neurotransmitter – a fast paracrine
chemical signal released by a neuron that
influences the neuron’s target cell
immediately
Posterior Lobe of the Pituitary Gland (Neurohypophysis)
Neurohypophysis –
Posterior lobe of pituitary gland
Made of axons of hypothalamic nerves
Neurons of the supraoptic nucleus manufacture antidiuretic hormone (vasopressin)
Decreases the amount of water lost at the kidneys
Elevates blood pressure
Neurons of the paraventricular nucleus manufacture oxytocin
Stimulates contractile cells in mammary glands
Stimulates smooth muscle cells in uterus
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Oxytocin
Oxytocin is a strong stimulant of uterine contraction
Regulated by a positive feedback mechanism to
oxytocin in the blood
This leads to increased intensity of uterine
contractions, ending in birth
Oxytocin triggers milk ejection (“letdown” reflex) in women
producing milk
Synthetic and natural oxytocic drugs are used to induce or hasten labor
Plays a role in sexual arousal and satisfaction in males and non-lactating females
Antidiuretic Hormone (ADH)
ADH helps to avoid dehydration or water overload - prevents
urine formation
Osmoreceptors monitor the solute concentration of the blood
With high solutes, ADH is synthesized and released, thus
preserving water
With low solutes, ADH is not released, thus causing water
loss from the body
Alcohol inhibits ADH release and causes copious urine
output
Thyroid Gland
The largest endocrine gland composed of colloid-filled follicles
Colloid = thyroglobulin + iodine fills the lumen of the follicles and is the
precursor of thyroid hormone
Thyroid hormones end up attached to thyroid binding globulins
(TBG) produced by the liver; some are attached albumin (protein
carrier)
Other endocrine cells, the parafollicular cells (C cells), produce the
hormone calcitonin
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Thyroid Gland
Thyroid hormones
T3 and T4 are two closely related iodine-containing compounds
T3 and T4 are non-steroid hormones
Triiodothyronine (T3) has two tyrosines with three bound iodine atoms
Thyroxine (T4) has two tyrosine molecules plus four bound iodine atoms
T4 and T3 circulating in blood bound to thyroxine-binding globulins (TBGs)
Both bind to target receptors, but T3 is ten times more active than T4
Mechanisms of activity are similar to steroids
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Thyroid hormones
Regulates metabolism
Promotes glycolysis, gluconeogenesis, glucose uptake
Glucose oxidation
Increasing metabolic rate
Heat production
Regulates growth and development
Regulates tissue growth
Increases protein synthesis
Developing skeletal and nervous systems
Maturation and reproductive capabilities
C Cells produce Calcitonin - helps regulate calcium concentration in
body fluids
Helps maintaining blood pressure
Regulation of Thyroid Hormones
Regulation is by negative feedback loop (NFbL)
Stimulus: Low circulating T3,T4 detected by hypothalamus and adenohypophysis
Hypothalamic Thyrotropin-Releasing Hormone (TRH) can override the short-loop negative feedback
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Homeostatic Regulation of Calcium Ion
Concentrations
Thyroid gland produces calcitonin
Increased excretion of calcium in
kidneys
Calcium deposition in bone
Inhibition of osteoclasts
>> Calcium levels decline
Parathyroid gland secretes parathyroid
hormone (PTH)
Release of stored calcium from
bone
Stimulation of osteoclasts
Enhanced reabsorption of calcium
in kidneys
Stimulation of calcitriol production at
kidneys; enhanced Ca2+, PO4-3,
absorption by digestive tract
>> Calcium levels rise
*Normal calcium levels: 8.5 – 11 mg/dL
Adrenal (Suprarenal) Glands
Adrenal glands – paired, pyramid-shaped organs atop the kidneys
Structurally and functionally, they are two glands in one
Adrenal medulla –
nervous tissue that functions as part of the Sympathetic Nervous System
secretes catecholamines:
Epinephrine (~75 – 80%)
Norepinephrine (~25 – 30%)
Adrenal cortex
glandular tissue derived from embryonic mesoderm
secretes corticostaeroids:
Mineralocorticoids
Glucocorticoids,
Gonadocorticoids
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Adrenal Cortex
Adrenal Cortex synthesizes and releases steroid hormones called corticosteroids
Different corticosteroids are produced in each of the three layers
Zona glomerulosa – mineralocorticoids (aldosterone)
Zona fasciculata – glucocorticoids (cortisol)
Zona reticularis – gonadocorticoids (sex hormones)
Adrenal Cortex
Secretes over 30 different steroid hormones (corticosteroids)
Mineralocorticoids
Aldosterone: maintains electrolyte balance
Glucocorticoids
Cortisol:
Stimulates gluconeogenesis
Mobilization of free fatty acids
Glucose sparing
Anti-inflammatory agent
Gonadocorticoids
testosterone, estrogen, progesterone
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Mineralocorticoids
Regulate the electrolyte concentrations of extracellular fluids
Aldosterone – most important mineralocorticoid
Maintains Na+ balance by reducing excretion of sodium from the
body
Stimulates reabsorption of Na+ by the kidneys
Aldosterone secretion is stimulated by:
Rising blood levels of K+
Low blood Na+
Decreasing blood volume or pressure
Glucocorticoids (Cortisol)
Help the body resist stress by:
Keeping blood sugar levels relatively constant
Maintaining blood volume and preventing water shift into tissue
Cortisol provokes:
Gluconeogenesis (formation of glucose from non-carbohydrates)
Rises in blood glucose, fatty acids, and amino acids
Gonadocorticoids (Sex Hormones)
Most gonadocorticoids secreted are androgens (male sex hormones), and the most important one is
testosterone
Androgens contribute to:
The onset of puberty
The appearance of secondary sex characteristics
Sex drive in females
Androgens can be converted into estrogens after menopause
Pancreas
Pancreatic islets - clusters of endocrine cells within the pancreas (Islets
of Langerhans)
α-cells secrete Glucagons
raises blood glucose by increasing the rates of glycogen
breakdown (glycogenolysis) and glucose manufacture by
the liver
β-cells secrete Insulin
lowers blood glucose by increasing the rate of glucose uptake and utilization
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Regulation of Blood Glucose Concentrations
Normal Blood Glucose Level (BGL): 70 – 110 mg/dL
BGL rises >> β cells secrete insulin:
Increased rate of glucose transport into target cell
Increased rate of glucose utilization and ATP generation
Increased conversion of glucose to glycogen (liver, skeletal muscle)
Increased amino acid absorption and protein synthesis
Increased triglyceride synthesis (adipose tissue)
>> Blood glucose concentration declines
BGL drops >> α cells secrete glucagon:
Increased breakdown of glycogen to glucose (liver, skeletal muscle)
Increased breakdown of fats to fatty acids (adipose tissue)
Increased synthesis and release of glucose (liver)
>> Blood glucose concentration rises
Multiple Stimuli for Hormone Release: Nervous & Endocrine
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Regulation of Glucose Metabolism During Exercise
Glucagon secretion increases during exercise to promote liver glycogen breakdown (glycogenolysis)
Epinephrine and Norepinephrine further increase glycogenolysis
Cortisol levels also increase during exercise for protein catabolism for later gluconeogenesis.
Growth Hormone mobilizes free fatty acids
Thyroxine (T4) promotes glucose catabolism
Regulation of Glucose Metabolism During Exercise
As intensity of exercise increases, so does the rate of catecholamine release for glycogenolysis
During endurance events the rate of glucose release very closely matches the muscles need.
When glucose levels become depleted, glucagon and cortisol levels rise significantly to enhance
gluconeogenesis.
Regulation of Glucose Metabolism During Exercise
Glucose must not only be delivered to the cells, it must also be taken up by them. That job relies on
insulin.
Exercise may enhance insulin’s binding to receptors on the muscle fiber.
Up-regulation (receptors) occurs with insulin after 4 weeks of exercise to increase its sensitivity
(diabetic importance)
Regulation of Fat Metabolism During Exercise
When low plasma glucose levels occur, the catecholamines are released to accelerate lypolysis
Triglycerides are reduced to free fatty acids (lipolysis) by lipase which is activated by:
Cortisol
Epinephrine
Norepinephrine
Growth Hormone
Hormonal Effects on Fluid and Electrolyte Balance
Reduced plasma volume leads to release of aldosterone which increases Na+ and H2O reabsorption by
the kidneys and renal tubes.
Antidiuretic Hormone (ADH) is released from the posterior pituitary when dehydration is sensed by
osmoreceptors, and water is then reabsorbed by the kidneys.
Hormones and Stress
Stress - any condition that threatens homeostasis
GAS (General Adaptation Syndrome) is our bodies response to stress-causing factors
Three phases to GAS:
Alarm phase (immediate, fight or flight, directed by the sympathetic nervous system)
Resistance phase (dominated by glucocorticoids)
Exhaustion phase (breakdown of homeostatic regulation and failure of one or more organ
systems)
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Stress and the Adrenal Gland
The General Adaptation Syndrome
Resistance Phase (Long-term metabolic adjustments)
Mobilization of remaining energy reserves:
Lipolysis: Lipids are released from
adipose tissue
Proteolysis: Amino acids are released
from skeletal muscle
Conservation of glucose
Peripheral tissue (except neural) breaks down
lipids to obtain energy
Elevation of blood glucose level (BGL)
Gluconeogenesis:
Liver synthesizes glucose from other
carbohydrates, amino acids, and lipids
Conservation of Na+ and H2O; loss of K+ and H+
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