Chapter 18 -2
Endocrine Glands
Comparison of neuronal and endocrine as
communication channels
The neuronal system:
Has clear pathways which are connected with
neurons. Thus it is reasonably clear for each neuron
where it starts and where it ends.
At the end, knob, a neurotransmitters is released.
Its complexity makes it possible to stimulate more
than one tissue and organs simultaneously.
The effect is relatively short lived.
Chemical Signals
• Intercellular: Allow one cell to
communicate with other cells as hormones
– Autocrine
• Released by cells and have a local effect on same
cell type from which chemical signals released as
prostaglandin
– Paracrine
• Released by cells and affect other cell types locally
without being transported in blood as somatostatin
– Pheromones
• Secreted into environment that modify behavior and
physiology as sex pheromones
Chemical Structure of Hormones
Control of Secretion Rate
• Most hormones are not secreted at constant rate
• Patterns of regulation
– Involves action of substance other than hormone on an endocrine
gland
– Involves neural control of endocrine gland
– Involves control of secretory activity of one endocrine gland by
hormone or neurohormone secreted by another endocrine gland
3.
Control of secretion rate
In essence the control is in a form of negative
feedback. Three major patterns:
a.
By other substance; Such as sugar
control the regulation of insulin release.
Increased blood sugar
Stimulates insulin release from the
pancreas
Insulin stimulates glucose uptake by
tissues
Results in decreased blood sugar
There are three major types of hormone structures: (Table 17.2
and Fig. 17.3)
i.
Amino acid derivatives: Epinephrine,
Norepinephrine, the thyroid hormones, pineal
hormone (melatonin)
ii.
Peptide/protein hormone: Antidiuretic
hormone, glucagon, oxytocin, growth hormone,
prolactin, insulin.
iii. Lipid derivatives:
a. Steroid hormones. Estrogens, testosterone,
b. Prostaglandins. Derived from arachidonic acid.
REVIEW of the mechanisms of hormonal action
The action of hormone is usually by activation of
cytosolic enzymes or DNA.
But, first, the hormones identify the target cells by
the receptors on the membrane (epinephrine,
Norepinephrine, peptide hormones) or in the
cytoplasm (steroid hormones) or the nucleus
(thyroid hormones).
The hormones which attack the target receptors on
the membrane do not usually permeate through the
membrane. These are first messengers.
The first messenger binds the receptor on the membrane and
triggers the release of the second messenger.
Hormone - receptor - release of cyclic AMP - activation of
adenylate cyclase - ATP becomes cyclic-AMP
Cyclic-AMP can activate enzymes specific to a cell.
Thus, one hormone can have effect on many different types of
cells.
Other second messengers are Ca++ and cyclic-GMP.
Thyroid and steroid hormones have effects directly on the
nucleus or indirectly through cytosol.
These hormones affect protein synthesis e.g. anabolic steroid
hormone.
Control of endocrine activity
The regulation of endocrine activity with the
hypothalamus is a good example of how the nervous
system and endocrine system integrate (Fig. 18-5).
In addition, the activity of endocrine cells may be in
response to its environment by negative feedback.
For example:
If circulating Ca++ levels go down - Parathyroid
hormone is released - Target cell elevates Ca++ level Increased Ca++ level - Releases Calcitonin - lowered
Ca++ level
Always prepare to ask:
Where is the gland found?
How does it look like?
What stimulates the gland?
What hormone does it release?
What is the target organ(s)?
Ultimately, what does it do?
Endocrine System Functions
•
•
•
•
•
•
•
•
Metabolism and tissue maturation
Ion regulation
Water balance
Immune system regulation
Heart rate and blood pressure regulation
Control of blood glucose and other nutrients
Control of reproductive functions
Uterine contractions and milk release
Pituitary Gland and Hypothalamus
Note the direction of the face
• Where nervous and
endocrine systems interact
• Pituitary gland/hypophysis
– Secretes 9 major hormones
• Hypothalamus
– Regulates secretory activity
of pituitary gland through
neurohormones and action
potentials
– Posterior pituitary is an
extension of the
hypothalamus
Pituitary Gland Structure
• Posterior or neurohypophysis
– Continuous with the brain
– Secretes neurohormones
• Anterior or adenohypophysis
– Consists of three areas with indistinct boundaries: pars
distalis, pars intermedia, pars tuberalis
This small hypophysis (pituitary gland): (Fig. 18-6) is
located under the hypothalamus, excretes 9 major
peptide hormones which are regulated by hypothalamus
and exhibits profound effects on many tissue and
organs.
a.
The Structure
I cm in diameter
0.5 - 1g
Sits on the sella turcica of the sphenoid bone
Connected to hypothalamus through infundibulum.
Divided into
Posterior pituitary (neurohypophysis)
Anterior pituitary (adenohypophysis)
b.
Posterior Pituitary
Developmentally, it is an extension of the brain
Releases neurohormones
c.
Anterior Pituitary
Developmentally, traces back to the oral cavity
called Rathke’s pouch.
Divided into three distinctive areas:
The pars tuberalis
The pars distalis
The pars intermedia
Releases endocrine hormones
d.
Regulation of
pituitary by
hypothalamus
i.
The anterior
pituitary (Fig. 18-7)
In the region pituitary connects with hypothalamus and anterior
pituitary, there are two capillary networks:
Hypothalamohypophyseal portal system as the primary capillary
network
Secondary capillary network in anterior pituitary.
Neurohormones released from hypothalamus enter the primary
capillary.
The hormones carried to the secondary capillary and released into
anterior pituitary.
These hormones may either increase or inhibit the excretion of
hormones from the anterior pituitary.
Hormones from the anterior pituitary, then will be carried by the
circulatory system.
Note the number of neurohormones released
from the hypothalamus that affect the anterior
pituitary gland. (Fig. 18-8a,b) Most of them are
small peptides
ii.
The posterior pituitary (Fig 18-7)
As for the posterior pituitary, there is no
connecting portal system.
The neurosecretory cells from the hypothalamus
extend to the posterior pituitary through
hypothalamohypophyseal tract.
The neurohormones will be released into the
portal system of the posterior pituitary.
Hypothalamus, Posterior
Pituitary Gland
Pituitary Gland Hormones
Mostly peptides, proteins or glycoproteins.
• Posterior
– Antidiuretic hormone
(ADH)
– Oxytocin
• Anterior
– Growth hormone (GH) or
somatotropin
– Thyroid-stimulating
hormone (TSH)
– Adrenocorticotropic
hormone (ACTH)
– Melanocyte-stimulating
hormone (MSH)
– Luteinizing hormone (LH)
– Follicle-stimulating
hormone (FSH)
– Prolactin
Anterior Pituitary Hormones
Hormone secretion is regulated by the
neurohormones from the hypothalamus.
Growth hormone GH (protein): Targets many
cells and over all increase in metabolism.
Control of GH secretion is shown in Seeley’s Fig.
18.6.
Growth Hormone (GH)
• Stimulates uptake of
amino acids and
conversion into proteins
• Stimulates breakdown of
fats and glycogen
• Promotes bone and
cartilage growth
• Increased secretion in
response to increase
amino acids, low blood
glucose, or stress
• Regulated by GHRH and
GHIH or somatostatin
Thyroid-stimulating hormone TSH
(glycoprotein): Targets the thyroid gland and
increase thyroid hormone release
Adrenocorticotropic hormone ACTH (peptide):
Targets the adrenal cortex and increase
glucocorticoid hormone secretion.
These hormone, which stimulate release of
hormones from other endocrine glands are
called “tropic hormones”
The gonadotropins include follicle-stimulating hormone,
luteinizing hormone and prolactin and regulate activity of
gonads. They are under regulation of gonadotropin
releasing hormone (GnRH) from the hypothalamus.
Follicle-stimulating hormone promotes follicle development
in females and together with LH stimulates release of
estrogens. In males FSH stimulates sustentacular cell
formation. FSH production is inhibited by inhibin.
Luteinizing hormone induces ovulation, promotes secretion
of the estrogens and the progesterone. More later.
Prolactin stimulates mammary gland development, milk
production.
ii.
Posterior Pituitary Hormones
The posterior pituitary stores and releases two polypeptide
neurohormones formed in the hypothalamus and
transmitted through hypothalamohypophyseal nerve tract:
Antidiuretic hormone (ADH): prevents production of large
quantity of urine. It is also vasopressin and constricts
blood vessels. Control of ADH secretion is shown in
Seeley’s Fig. 18.5.
Oxytocin: stimulates the smooth muscle cells of the
uterus. Important for expulsion of the fetus. Milk ejection.
Question: Does the posterior pituitary gland make its own
hormone?
Antidiuretic Hormone
• Also called vasopressin
• Promotes water retention by kidneys
• Secretion rate changes in response to alterations in blood
osmolality and blood volume
• Lack of ADH secretion is a cause of diabetes insipidus
Oxytocin
• Promotes uterine contractions during
delivery
• Causes milk ejection in lactating women
Thyroid Gland
• One of largest endocrine
glands
• Highly vascular
• Histology
– Composed of follicles
– Parafollicular cells
• Secrete calcitonin which
reduces calcium
concentration in body
fluids when levels elevated
Hormones of the thyroid
The follicular cells of the thyroid gland (Fig. 1812) release derivatives of tyrosine to which
three or four iodine molecules are attached,
thus
triiodothyronine (T3)-10%
tetraiodothyronine (T4)-90% - thyroxine.
Parafollicular cells (Fig. 18.7b,c) release
calcitonin.
Thyroid Hormones
• Include
– Triiodothryronine or T3
– Tetraiodothyronine or T4 or thyroxine
• Transported in blood
• Bind with intracellular receptor molecules and initiate new
protein synthesis
• Increase rate of glucose, fat, protein metabolism in many
tissues thus increasing body temperature
• Normal growth of many tissues dependent on
Synthesis of T3 and T4
Thyroid hormone synthesis requires thyroid stimulating
hormone (TSH) from the anterior pituitary and iodine. (Fig.
18-12a)
Secretion of thyroid hormone is initiated by TSH. (Fig.
18-12b and Seeley Fig. 18.9.)
In fact, it starts with a release of TRH from the
hypothalamus, to the hypothalamohypophyseal portal
system of the anterior pituitary, where TSH is released.
TSH reaches the thyroid gland through the circulatory
system and regulate the secretion of T3 and T4.
Regulation of T3 and T4 Secretion
Transporting thyroid hormones
Thyroid hormones are transported through the
circulatory system bound with thyroxin-binding
globulin (TBG) The binding helps the half-life
of the hormones to increase to 1 week in the
circulatory system. During this period thyroxin
(T4) may convert to T3, which is the more
active form
f.
The targets of thyroid hormones
Thyroid hormones affect many cells, but not exactly in
the same manner. They affect metabolism, growth and
maturation.
They permeate through the membrane and bind with
the receptors in the nuclei to react with the DNA for
protein synthesis.
Thyroid hormone may interact with mitochondria and
produce more ATP and hence heat production.
It requires about 1 week for the thyroid hormones to
take effect.
Thyroid Hormone Hyposecretion
and Hypersecretion
• Hypothyroidism
– Decreased metabolic rate
– Weight gain, reduced
appetite
– Dry and cold skin
– Weak, flabby skeletal
muscles, sluggish
– Myxedema
– Apathetic, somnolent
– Coarse hair, rough dry skin
– Decreased iodide uptake
– Possible goiter
• Hyperthyroidism
– Increased metabolic rate
– Weight loss, increased
appetite
– Warm flushed skin
– Weak muscles that exhibit
tremors
– Exophthalmos
– Hyperactivity, insomnia
– Soft smooth hair and skin
– Increased iodide uptake
– Almost always develops
goiter
Parafollicular cells and Calcitonin
Increased level of Ca++ stimulates the release
of calcitonin from the Parafollicular cells.
The target is bone tissue and decreases
osteoclast activity, thus increases the life span
of osteoblasts.
Thus decreases blood Ca++ and phosphates.
Therefore, blood calcium level may be
regulated with calcitonin.
Parathyroid Glands
• Embedded in thyroid
• Secrete PTH
– Increases blood
calcium levels
– Stimulates osteoclasts
– Promotes calcium
reabsorption by
kidneys
c.
Targets and Function
Parathyroid hormone (PTH) regulates calcium levels and
targeted to bone, the kidneys and the intestine.
The action is opposite to calcitonin
PTH stimulates, for example
Osteoclast activity in bone tissue leading to bone resorption
and the release of calcium and phosphate, i.e. increased
blood Ca++ (,but not necessarily phosphate).
Induces Ca++ reabsorption in the kidneys to increase
enzyme activity to form vitamin D.
Inactive parathyroid glands, due to lack of Ca++ increase in
blood by PTH, lead to hypocalcemia - nervousness, spasm,
etc.
Adrenal Glands
• Functions as part of sympathetic nervous system
• Composed of medulla and cortex (3 layers)
• Hormones
– Medulla secretes epinephrine and norepinephrine
– Cortex secretes mineralocorticoids, glucocorticoids, androgens
Hormones of Adrenal Cortex
• Mineralocorticoids
– Zona glomerulosa
– Aldosterone produced in greatest amounts
• Increases rate of sodium reabsorption by kidneys increasing
sodium blood levels
• Glucocorticoids
– Zona fasciculata
– Cortisol is major hormone
• Increases fat and protein breakdown, increases glucose
synthesis, decreases inflammatory response
• Androgens
– Zona reticularis
– Converted to androgen and testosterone
Pancreas
• Located along small intestine
and stomach
• Exocrine gland
– Produces pancreatic digestive
juices
• Endocrine gland
– Consists of pancreatic islets
– Composed of
• Alpha cells secrete glucagon
• Beta cells secrete insulin
• Delta cells secrete
somatostatin
The exocrine portion consists of Acini that
produces pancreatic juice (enzymes) and a duct
system.
The endocrine part consists of pancreatic islets
(islets of Langerhans) separated into:
Alpha cells (glucagon production, protein)
Beta cells (insulin production, polypeptide).
Delta cells (somatostatin, peptide)
F Cells (pancreatic polypeptide PP)
c.
Hormones of the pancreas (Table 18-6)
Insulin is a protein, glucagon is a polypeptide, and
somatostatin is a peptide.
i. Insulin
Produced in beta cells in response to rising blood glucose
and amino acids. Targets the liver, adipose tissue,
muscles the hypothalamus.
Insulin binds to the receptor on the membrane and
stimulates glucose transport into the cells. Glucose, once
inside the cell, is metabolized to make energy, glycogen,
amino acids, proteins, fats, etc.
Glucose uptake by the kidneys, lining of digestive tracts,
red blood cells and brain cells is independent of insulin.
ii.
Glucagon
Secreted from alpha cells when blood glucose levels
fall.
In the liver, it stimulates glycogenolysis (glycogen
hydrolysis) and releases glucose into circulation..
In adipose tissue it initiates breaking down of fats and
releases free fatty acids and ketone bodies.
It also responds to blood amino acids after high
protein meal.
iii. Somatostatin
Produced in delta cells of islets when blood glucose
and amino acids rise after a meal.
It behaves as a paracrine secretion (chemical
messenger that diffuses to neighboring target cells, i.
e. alpha and beta cells.).
Thus modulates their activities.
Insulin and Glucagon
Insulin
• Target tissues: liver,
adipose tissue, muscle,
and satiety center of
hypothalamus
• Increases uptake of
glucose and amino
acids by cells
Glucagon
• Target tissue is liver
• Causes breakdown of
glycogen and fats for
energy
Regulation of Blood Nutrient
Levels After a Meal
Regulation of Blood Nutrient
Levels During Exercise
Hormones of the Reproductive
System - more later
Male: Testes
• Testosterone
– Regulates production of
sperm cells and development
and maintenance of male
reproductive organs and
secondary sex characteristics
• Inhibin
– Inhibits FSH secretion
Female: Ovaries
• Estrogen and Progesterone
– Uterine and mammary
gland development and
function, external genitalia
structure, secondary sex
characteristics, menstrual
cycle
• Inhibin
– Inhibits FSH secretion
• Relaxin
– Increases flexibility of
symphysis pubis
Pineal Body
• In epithalamus
• Produces
– Melatonin
• Enhances sleep
– Arginine vasotocin
• Regulates function of
reproductive system in
some animals
b.
The kidneys
The kidneys release the steroid hormone
calcitriol, the peptide hormone erythropoietin and
the enzyme rennin.
Erythropoietin
Released from kidney when oxygen level is low.
Simulate synthesis of erythrocytes in the bone
marrow.
Calcitriol
In response to PTH, cholecalciferol (Vitamin D3) is
formed in the skin under the sun and eventually
becomes calcitriol. Calcitriol stimulates calcium and
phosphate absorption, stimulates Ca++ release from
bone, and inhibits PTH secretion. See Fig. 18-20
and Table 18-7 for details.
Renin
Response to the loss in renal blood flow reinangiotensin system is activated (See Fig. 18-20b)
Effects of Aging on
Endocrine System
• Gradual decrease in secretory activity of
some glands
–
–
–
–
GH as people age
Melatonin
Thyroid hormones
Kidneys secrete less renin
• Familial tendency to develop type II
diabetes
Diabetes Mellitus
• Results from inadequate secretion of insulin
or inability of tissues to respond to insulin
• Types
– Type I or IDDM (Insulin-dependent)
• Develops in young people
– Type II or NIDDM (Non-insulin dependent)
• Develops in people older than 40-45
• More common
Patients with Diabetes Mellitus have difficulty in
controlling their blood sugar level. The causes are
attributed to:
Inability to make insulin by the pancreatic islet
cells – Type I, IDDM
Lack of membrane receptor for insulin on
the cells of target tissues. – Type II, NIDDM
1.
The first type is called insulin dependent
diabetes mellitus (IDDM), since the patients may
be treated with insulin, or Type I diabetes.
It accounts for about 3% of the total diabetes
population.
It is assumed that the cause is related to the loss
of insulin production by pancreatic islets, possibly
due to an auto-immune disease.
The patients are primarily children.
2.
The second type is called non-insulin dependent
diabetes mellitus (NIDDM), since insulin does not
improve the condition of the patients, or Type II diabetes.
It accounts for 97% of the total diabetes population.
The target cells of insulin appear to have diminished
ability to produce insulin receptors, thus the effect of
insulin is declined.
The patients are mostly adult and sometime the disease
is referred to as adult on set diabetes.
Genetic linkage is suspected.
In addition to glucose tolerant test and others, chronic
severity of the disease may be assessed by the level of
HbAIC, which is a glucose bound (glycated) hemoglobin.
Glucose binds to hemoglobin spontaneously and the
degree of bound glucose is proportional to the level of blood
glucose, since glucose permeates the membrane of red
blood cells almost freely.
Thus, the higher the concentration of blood glucose the
higher the percentage of HbAIC The value could go as high
as 15% compared with 2-3% of the normal subject.