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The Endocrine System

B. Pimentel, M.D.
University of Makati
College of Nursing
Functional Organization

• Endocrine system are composed of glands that


secrete chemical signals into the circulatory
system.
• Endocrine Glands – secret chemicals into the
body.
• Hormones – secretory products of endocrine
glands, chemical signal
• Ligand – chemical signal of the hormone.
– Produced in small quantities by a group of cells.
– Secreted into the interstitial space
– Enters circulatory system, where it is transported
– Enters a target tissue, where it imparts an influence
on the function of that tissue.
Nervous and Endocrine System

Amplitude Modulated Signals

• Hormones secreted by most endocrine glands

• Either an increase or decrease in hormone


secretion

• Concentration of the hormone in the circulatory


has a direct response on the target tissue
Nervous and Endocrine System

Frequency Modulated Signals

• All or none principal of the nervous system

• Low frequency or low action potential will result


in a weak signal

• Strong action potential will result in a strong


response to the stimulus.
Nervous and Endocrine System

Response

• Endocrine system often has a slower and


longer duration of action on target tissues and
is more generally distributed throughout the
body.
• Nervous system faster response and shorter
duration than the endocrine system

Exceptions:
• Neurohormones released by neurons secrete
into the circulatory system and function similar
to endocrine hormones.
• Some neurons directly innervate endocrine
glands and influence the secretory activity.
Intercellular Chemical Signals

Intercellular Description Example


Chemical
Signals
Autocrine Secreted by cells in a local area Prostaglandins
and influences the activity of the
same cell type from which it was
secreted.
Paracrine Produced by a range of tissues Histamine
and secreted into tissue spaces; Prostaglandin
usually has a localized effect on  
other tissue.
Hormone Secreted into the blood by Thyroxine,
specialized cells, travels some Insulin
distance to target tissues,
influences specific activities.
Intercellular Chemical Signals

Intercellular Description Example


Chemical Signals

Neurohormone Produced by axons and Oxytocin,


function as hormones Antidiuretic
hormone
Neurotransmitter Produced by neurons and Acetylcholine
or secreted into the extracellular Epinephrine
neuromodulator space by presynaptic nerve
terminals, travels short
distances, influences post
synaptic cells.

Pheromone Secreted into the Sex


environment, modifies pheromones
physiology and behavior of
other individuals.
Structural Categories of Hormones
Category Examples
Proteins Growth hormone, Prolactin, Insulin
Glycoprotein Follicle stimulating hormone
Lutenizing hormone
Thyroid stimulating hormones
Parathyroid hormone
Polypeptides Thyrotropin releasing hormones
Oxytocin
Antidiuretic hormone
Calcitonin
Glucagon
Adrenocorticotropin hormone
Endorphins
Thymosin
Melanocyte stimulating hormones
Hypothalamic hormones
Lipotropins
Somatostatin
Structural Categories of Hormones

Category Examples

Amino Acid derivatives Epinephrine


Norepinephrine
Thyroid hormones (T3 & T4)
Melatonin

Lipids Estrogens
Steroids (cholesterol Progestins
precursor) Testosterone
Mineralcorticoids
Glucocorticoids
Structural Categories of Hormones

Category Examples

Lipids Prostaglandins
Fatty acid Thromboxanes
Prostacyclins
Leukotrienes
Regulation of Hormones

1. Non Hormonal Regulation of Hormone


secretion. Glucose a carbohydrate in the blood
stream regulates the secretion of insulin
(hormone).

a.    Increased blood glucose stimulates increased


insulin secretion from the pancreas.

b.     Insulin increases uptake of glucose by cells,


which
decreases levels of glucose in the blood.
Regulation of Hormones

2.  Nervous system regulation of hormonal


secretion. The sympathetic division of the
nervous system. The adrenal gland secretes
epinephrine or Norepinephrine (fight or flight).

a.    Stimuli such as stress or exercise activates the


sympathetic nervous system.

b.    Neurons stimulate the release of epinephrine and


smaller amounts of Norepinephrine from the
adrenal medulla
Regulation of Hormones

3.   Hormonal regulation of hormone secretion.


Hormones can stimulate or inhibit the secretion
of other hormones.

a.    Thyroid releasing hormone (TRH) is released from


neurons in the hypothalamus and travels in the
blood to the anterior pituitary gland.

b.    TRH stimulates the release of thyroid stimulating


hormone (TSH) from the anterior pituitary gland.
TSH travels in the blood to the thyroid gland.
Regulation of Hormones

c.    TSH stimulates the secretion of thyroid hormones


(T3 & T4) from the thyroid gland into the blood
stream.

d.    Thyroid hormones act on tissues.

e. Thyroid hormones also have a negative feed back


effect on the hypothalamus and the anterior
pituitary to inhibit both TRH and TSH secretion.
This negative feed back helps keep blood thyroid
hormone levels within a normal range.  
Transport and Distribution

• Hormones are dissolved in blood plasma and


transported either in a free form or bound to a
plasma protein.

• As the concentration of the free form hormone


in the blood increases, they will diffuse to
target cells.

• As the concentration of the free form hormone


decreases there are decreased diffusion, and
fewer target cells affected.
Transport and Distribution

• Hormones that are bound to plasma proteins


are in equilibrium with the free form hormone.

• Each hormone will have a specific plasma


protein

• Hormones bound to plasma proteins remain at


a relatively constant concentration.

• A large decrease in the plasma protein


concentration can result in the loss of a free
form hormone from the blood.
Binding to Target Cells

1. Binding site – portion of a protein or


glycoprotein where a Ligand will bind

2. Receptor Site – a protein or glycoprotein


receptor, where the receptor site allows only a
specific type of Ligand to bind.

3. Specificity – the tendency for each type of


Ligand to bind to a specific type of receptor,
and not others.
Binding to Target Cells
Binding to Target Cells

4. Membrane bound receptors – receptors for


ligands that span across the plasma membrane
and have their receptor sites exposed
extracellularly.
– Examples; large hormones that are proteins
glycoproteins, polypeptides, and some smaller
molecules such as epinephrine and Norepinephrine.

5. Intracellular receptors – are for lipid soluble


ligands that can pass through the plasma
membrane. Example; thyroid, testosterone,
estrogen, progesterone, aldosterone, and
cortisol.
Binding to Target Cells
Down Regulation

• The rate at which receptors are synthesized


decreases in some cells after exposure to a
Ligand.

• The combination of ligands and receptors can


increase the rate at which the receptor
molecules are degraded.

• Tissues that exhibit down regulation of


receptor molecules are adapted to respond to
short-term increases of the hormone
concentration.
Down Regulation

Example:
– Gonadotropin releasing hormone (GnRH), which is
released from neurons of the hypothalamus →
secretion of LH (leutinizing hormone) and follicle
stimulating hormone (FSH) from the anterior pituitary
cells → number of GnRH receptors molecules in the
pituitary to decrease several hours after exposure to
the hormone
Up Regulation

• Periodic increases in the sensitivity of some


cells to hormones.

• Increase of receptor molecule synthesis.

Example:
– increased number of receptor molecules for
leutinizing hormone (LH) in cells of the ovary during
each menstrual cycle. Follicle stimulating hormone
(FSH) molecules secreted by the pituitary increase
the rate of LH receptor molecule synthesis in cells of
the ovary.
Pituitary Gland

• 1cm. Diameter, 0.5 to 1.0 grams.


• Located on the sella turcica, inferior to the
hypothalamus and is connected to it by a stalk
of tissue the infundibulum.
• Divided into two functioning parts
– Posterior Pituitary or Neurohypophysis
• Continuous with the brain
– Anterior Pituitary or Adenohypophysis
Pituitary Gland
Pituitary Gland

Communication of the Pituitary and the


Brain

• Hypothalamohypophysial Portal System –


extends from the hypothalamus to the anterior
pituitary.

• Act as either releasing hormones – increasing


secretion of the anterior pituitary, or inhibiting
hormones – decreasing the secretions of
anterior pituitary hormones
Pituitary Gland

Stimulating Hormone Inhibiting Hormone Effects

Thyroid-stimulating Release of thyroid


hormone releasing stimulating hormone
hormone (TRH)
Corticotropin-releasing Release of
hormone (CRH) adenocorticotropic
hormone (ACTH)

Growth-hormone Release of growth


releasing hormone hormone
(GHRH)
Growth-hormone Inhibits the release
inhibiting hormone of growth hormone
(GHIH)
Pituitary Gland

Stimulating Hormone Inhibiting Hormone Effects

Somatostatin Inhibits the release of


growth hormone

Gonadotropin-releasing Release of luteinizing


hormone (GnRH) hormone (LH) and
Follicle stimulating
hormone (FSH)

Prolactin-inhibitory Inhibits prolactin secretion


factor
Pituitary Gland

Hormones Target Tissue Response

Posterior    

Antidiuretic Kidney Increased water


Hormone reabsorption
Oxytocin Uterus, mammary Increased uterine
glands contractions, increased
milk expulsion
Pituitary Gland

Hormones Target Tissue Response

Anterior    

Growth Most tissues Increased; growth in


Hormone tissues, amino acid
uptake and protein
synthesis, breakdown of
lipids and release of fatty
acids, glycogen
synthesis, blood glucose
levels, and somatomedin
production.
Pituitary Gland

Hormones Target Tissue Response

Thyroid Thyroid gland Increased thyroid


stimulating hormone secretion
Hormone (TSH)

Adrenocorticotr Adrenal cortex Increased glucocorticoid


opic Hormone hormone secretion
(ACTH)

Lipotropins Fat tissue Increased fat breakdown


Pituitary Gland

Hormones Target Tissue Response

Beta endorphins Brain Analgesia in the brain,


inhibition of gonadotropin
releasing hormone

Melanocyte Melanocytes Increased melanin


Stimulating production to make skin
Hormone (MSH) darker

Luteinizing Ovaries Ovulation and


Hormone (LH) Testes progesterone production
in ovaries; testosterone
synthesis and support for
sperm cell production in
testes
Pituitary Gland

Hormones Target Tissue Response

Follicle Follicles in ovaries in Follicle maturation and


Stimulating females; seminiferous estrogen secretion in
Hormone (FSH) tubules in males ovaries; sperm cell
production in males
Prolactin Ovaries and mammary Milk production in
glands lactating women;
increased response of
follicle to LH and FSH.
 
Antidiuretic Hormone (ADH)

• Transported to and stored in the posterior


pituitary.

• Released in blood stream to the kidneys.

• Functions in the regulation of osmolality and


volume of the extracellular fluid.
Oxytocin

• Stimulates smooth muscle cells of the uterus.

• Responsible for milk ejection in lactating


females.
Thyroid Gland

• Location: lateral to the superior portion of the trachea


just inferior to the larynx.

• Gross Anatomy: two lobes connected by a narrow band


of thyroid tissue called the isthmus.

• Histology: numerous follicles, which are small spheres,


composed of simple cuboidal epithelium. The center of
each follicle is filled with thyroglobulin to which thyroid
hormones are bound. Parafollicular cells are found
between follicles and produce and secrete Calcitonin.
Thyroid Gland

Hormones
• Triiodothyronine (T3) and tetraiodothyronine (T4) target
most cells of the body.
• Calcitonin targets bone tissue.

– TSH from the anterior pituitary must be present to maintain


thyroid hormone synthesis and secretion.
Thyroid Gland

Thyroid Hormone Synthesis

Iodide trapping in the follicular cells → iodide is


oxidized to iodine → released in to the follicular
colloid → combines with thyroglobulin →
mono/di-iodotyrosine (MIT, DIT) →
triiodotyrosine (T3), thyroxine (T4) bound to
thyroglobulin → re-enters the follicule cells by
pinocytosis → split by lysosomes from
thyroglobulin → free T3 and T4
Thyroid Gland (Regulation)

Stimulus

hypothalamus

TRH

Ant. pituitary

TSH

Thyroid gland Negative Feedback

T3/ T4

Target organ
Thyroid Gland (Regulation)
Parotid Glands

• Location: embedded in the posterior part of


each lobe of the thyroid gland. Four
parathyroid glands are present.

• Histology: cells are organized in densely


packed cords.
Parotid Glands

• Hormone: Parathyroid hormone regulates


calcium levels in body fluids. Targets bone,
kidneys, and intestines.

• Stimulates osteoclast activity in bone and can


cause the number of osteoclasts to increase.

• Increases calcium reabsorption in the kidneys

• The primary regulation for secretion of PTH is


blood calcium levels.
Vit. D, Kidneys and Parathyroid
Gland
Cholecalciferol
↓ (liver) Inhibition
25-Hydroxxholecalciferol
↓ (kidney) Activation Parathyroid hormone
1,25-Dihydroxycholecalciferol

Intestinal epithelium Inhibition

Intestinal absorption of calcium

Plasma calcium concentration
Adrenal Glands

• Location: superior poles of the kidneys.

• Gross Anatomy: surrounded by abundant


adipose tissue, enclosed in connective tissue
and have a well developed vascular supply.
They are composed of an inner medulla and an
outer cortex

• Histology: the medulla consists of closely


packed polyhedral cells centrally located in the
gland
Adrenal Glands
Adrenal Glands

Hormones
• Adrenal Medulla
– Epinephrine and Norepinephrine. Target tissues are
heart, blood vessels, liver and fat cells.

• Adrenal Cortex
– Three types: Mineralocorticoids, Glucocorticoids, and
Androgens.
Adrenal Glands

• Mineralocorticoids – aldosterone is the in the greatest


amount. Increases blood levels of sodium by
increasing the rate of sodium reabsorption in the
kidneys. Increases potassium secretion.

• Glucocorticoids – major one is cortisol. Targets many


cells and tissues. Increase fat catabolism, decrease
glucose and amino acid uptake in skeletal muscle,
increase gluconeogenesis, and increase protein
degradation. Also responsible for maturation of fetal
lungs

• Androgens – androstenedione, stimulates pubic and


axillary hair growth and sexual drive in females.
Adrenal Glands
Adrenal Steroid Synthesis

Cholesterol

Pregnenolone

Progesterone 17-OH-
Pregnenolone

17-OH-Progesterone

Aldosterone Cortisol Androgen


Regulation Of Cortisol Sercretion

Hypothalamus

CRH

Ant. pituitary

ACTH Adrenal cortex Negative Feedback

Cortisol
Pancreas

• Location: between the greater curvature of the


stomach and the duodenum.

• Gross Anatomy: elongated structure approx. 15


cm long. The head of the pancreas lies near
the duodenum, and its body and tail extend
toward the spleen.
Pancreas

• Histology: the pancreas is both an


exocrine and endocrine gland. The
exocrine portion contains acini, which
produce pancreatic enzymes, and a duct
to the small intestine. The endocrine
portion is composed of pancreatic islets
(islets of Langerhans). These islets
contain alpha, beta, and delta cells.
Pancreas

Cells in Hormone Target tissue Response


Islets

Beta Insulin Liver, skeletal Increased uptake and


muscle, adipose use of glucose and amino
tissue acids.

Alpha Glucagon Liver Increased breakdown of


glycogen, release of
glucose into the
circulatory system
Delta Somatostatin Alpha and beta Inhibition of insulin and
cells glucagon secretion
THE END

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