The Endocrine System

The Endocrine SystemB. Pimentel, M.D.

Univeristy of MakatiCollege 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


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.


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


Description Example

Autocrine Secreted by cells in a local area and influences the activity of the same cell type from which it was secreted.

Prostaglandins

Paracrine Produced by a range of tissues and secreted into tissue spaces; usually has a localized effect on other tissue.

Histamine Prostaglandin

Hormone Secreted into the blood by specialized cells, travels some distance to target tissues, influences specific activities.

Thyroxine, Insulin


Neurohormone Produced by axons and function as hormones

Oxytocin, Antidiuretic hormone

Neurotransmitter or neuromodulator

Produced by neurons and secreted into the extracellular space by presynaptic nerve terminals, travels short distances, influences post synaptic cells.

Acetylcholine Epinephrine

Pheromone Secreted into the environment, modifies physiology and behavior of other individuals.

Sex pheromones


Description Example

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


Amino Acid derivatives Epinephrine Norepinephrine Thyroid hormones (T3 & T4) Melatonin

Lipids Steroids (cholesterol precursor)

Estrogens Progestins Testosterone Mineralcorticoids Glucocorticoids

Category Examples


Lipids Fatty acid

Prostaglandins Thromboxanes Prostacyclins Leukotrienes

Category Examples

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.


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


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.


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.



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.


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 hormone releasing hormone (TRH)

Release of thyroid stimulating hormone

Corticotropin-releasing hormone (CRH)

Release of adenocorticotropic hormone (ACTH)

Growth-hormone releasing hormone (GHRH)

Release of growth hormone

Growth-hormone inhibiting hormone (GHIH)

Inhibits the release of growth hormone

Pituitary Gland

Somatostatin Inhibits the release of growth hormone

Gonadotropin-releasing hormone (GnRH)

Release of luteinizing hormone (LH) and Follicle stimulating hormone (FSH)

Prolactin-inhibitory factor

Inhibits prolactin secretion

Stimulating Hormone

Inhibiting Hormone

Effects

Pituitary Gland

Hormones Target Tissue Response

Posterior

Antidiuretic Hormone

Kidney Increased water reabsorption

Oxytocin Uterus, mammary glands

Increased uterine contractions, increased milk expulsion

Pituitary Gland

Anterior

Growth Hormone

Most tissues Increased; growth in 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

Thyroid stimulating Hormone (TSH)

Thyroid gland Increased thyroid hormone secretion

Adrenocorticotropic Hormone (ACTH)

Adrenal cortex Increased glucocorticoid hormone secretion

Lipotropins Fat tissue Increased fat breakdown


Pituitary Gland


Beta endorphins

Brain Analgesia in the brain, inhibition of gonadotropin releasing hormone

Melanocyte Stimulating Hormone (MSH)

Melanocytes Increased melanin production to make skin darker

Luteinizing Hormone (LH)

Ovaries Testes

Ovulation and progesterone production in ovaries; testosterone synthesis and support for sperm cell production in testes

Pituitary Gland


Follicle Stimulating Hormone (FSH)

Follicles in ovaries in females; seminiferous tubules in males

Follicle maturation and estrogen secretion in ovaries; sperm cell production in males

Prolactin Ovaries and mammary glands

Milk production in 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 CortisolAndrogen

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 Islets

Hormone Target tissue Response

Beta Insulin Liver, skeletal muscle, adipose tissue

Increased uptake and use of glucose and amino acids.

Alpha Glucagon Liver Increased breakdown of glycogen, release of glucose into the circulatory system

Delta Somatostatin

Alpha and beta cells

Inhibition of insulin and glucagon secretion

THE END

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The Endocrine System