Endocrine System

Carl B. Goodman, Ph.D.

College of Pharmacy & Pharmaceutical Sciences

Florida A&M University

308E FSH-SRC

599-3128

carl.goodman@famu.edu

Endocrine System: Homeostasis

Hormone- Regulatory molecules secreted into blood stream

Endocrine Gland- Ductless glands contains secretory cells- Synthesis or produce hormones

Effector- Target cells or tissues- Contains receptors to produce some physiological response

Endocrine System vs Nervous System

Function Nervous System Endocrine System

Secretory Cells Neuron Glandular Epithelial Cells &Neurosecretory Cells

Distance Short (Synapse) Long (Blood)

Location of Receptors Plasma Membrane Plasma Membrane In Effector Cells & Within the Cell

Characteristics of Appears Rapid, Slow, Long Lasting Regulatory Effects Short Lived

Diagram Pre & Post Synaptic Target Cells Neurons

Endocrine System vs Nervous System

Function Nervous System Endocrine System

Overall Function Regulate Effectors Regulate Effectors *HOMEOSTASIS *HOMEOSTASIS

Control Feedback Loop Yes (Nervous Reflex) Yes (Endocrine Reflex)

Chemical Messenger Neurotransmitter Hormone (Proteins or Steroids)

Effector Tissues Muscle & Glandular All Cell Types Tissues *Muscles, Bones,

Glandular

Effector Cells Post Synaptic Neurons Target Cells

Endocrine Action

Endocrine System

Endocrine Glands

CNS: Pituitary Gland

Periphery: Pancreas, Thyroid,

Parathyroid, Adrenal, Testes and Ovaries

Organs with Partial Endocrine Functions

Hypothalamus, Pineal Gland, Stomach, Duodenum, Liver, Thymus, Heart, Skin, Kidney, Lung and Placenta

Types of Hormones: Lipid Soluble

Steroids- Cortisol- Aldosterone- Androgens- Estrogen/Progesterone- Testosterone- Calcitrol (Kidney)

Gas- Nitric Oxide (NO)

Thyroids- Triiodothyronine (T3)

- Thyroxine (T4)

Types of Hormones: Water Soluble Glycoproteins

- Follicle Stimulating Hormone (FSH)- Luteinizing Hormone (LH)- Thyroid Stimulating Hormone (TSH)

Peptides- Anti-diuretic Hormone (ADH) (8 AA)- Oxytocin (8 AA)- Melanocyte Stimulating Hormone (MSH)- Thyroid Releasing Hormone (TRH)

Proteins- Growth Hormone (191), Calcitonin (32 AA), Prolactin, Insulin (21 & 30 AA), ACTH (39 AA), Parathyroid Hormone (84 AA)

Fatty Acids (Arachidonic acid) - Leukotrienes- Prostaglandins- Thromboxanes- Prostacyclins

Types of Hormones: Amino Acids Amines (Water Soluble)

- Norepinephrine (Tyrosine)- Epinephrine (Tyrosine)- Melatonin (Tryptophan)- Serotonin (Tryptophan)- Histamine (Histadine)

Iodinated Amino Acid - Thyroxine (T4)

- Triiodothyronine (T3)

Hormone Circulation Endocrine Action:

hormone is distributed in blood and binds to distant target cell

Paracrine Action:hormone acts locally by diffusing from its source to target cells in the neighborhood

Autocrine Action:hormone acts on the same cell that produced it

Hormone Transport in Blood

Protein hormones circulate in free form in blood

Steroid (lipid) & thyroid hormones must attach to transport proteins (Carrier Molecules) synthesized by liver– improve transport by making them water-soluble– slow loss of hormone by filtration within kidney– create reserve of hormone

• only .1 to 10% of hormone is not bound to transport protein = free fraction

Synthesis and Metabolism

General Mechanisms of Hormone Action

Hormone binds to cell surface or receptor inside target cell

Cell may then:– synthesize new molecules (Protein Synthesis)– change permeability of membrane (Ion channels)– alter rates of reactions (Enzymes)

Each target cell responds to hormone differently– Liver cells: insulin stimulates glycogen synthesis– Adipose: insulin stimulates triglyceride synthesis

Circadian Rhythm for all Hormones (Basal Level)- Ex. Cortisol: increased daytime and decreased at night

Hormone Interaction

Synergistic

Permissive- a second hormone, strengthens the effects of the firstEx. thyroid strengthens epinephrine’s effect upon lipolysis or Estrogen

and Progesterone are need for maturation of follicle

Antagonisticex. Insulin and Glucagon

Prehormone

ex. T4 converted to T3

ex. Vitamin D3 converted to 1,25 dihydroxyvitamin D3

Role of Hormone Receptors Constantly being synthesized & broken down

A range of 2,000-100,000 receptors / target cell

Down-regulation (Hypersecretion of Hormone)– excess hormone, produces a decrease in number of

receptors• receptors undergo Endocytosis and are degraded

– decreases sensitivity of target cell to hormone

Up-regulation (Hyposecretion of Hormone)– deficiency of hormone, produces an increase in the number

of receptors– target tissue more sensitive to the hormone

H + R = HR Complex

Intracellular Chemical Signal Autocrine: secreted in a local area ex. Prostaglandins

Paracrine: neighboring cell ex. Histamine, Prostaglandins

Hormone: secreted in blood… ex. Insulin, T4, and T3

Neurohormone: produced by neurons ex. Oxytocin, ADH

Neurotransmitter or Neurohumor: produced by neurons and secreted into synapse ex. Acetylcholine and Epinephrine

Pheromone: secreted in environment, modifies behavior ex. Sex pheromones

Hormone Signal Transduction Pathway

Steroids Hormone Protein Hormone

Second Messengers

cAMP cGMP Phospholipase C Ca++

Opposing 2nd Messenger System with Same Hormone Beta Adrenergic Receptors

- Relaxation/Dilation = cAMP

Alpha Adrenergic Receptors- Constriction = Phospholipase C

Feedback Control System

Negative Feedback Positive Feedback

Hypothalamic-Pituitary System

AdenohypophysisNeurohypophysis

Pituitary Gland = Hypophysis

Hypothalamic-Pituitary System

Pars Nervosa Pars Distalis

Pars Tuberalis

Pars Intermedia

Posterior Pituitary Gland: Neurohormones Anti-diuretic Hormone

(ADH) or Vasopressin Osmoreceptors near Supraoptic

Nucleus (Dehydration) (Alcohol)

H2O is reabsorbed from the tubules of the kidney and returned to the blood instead of the urine (H20 is conserved)

Decrease in rate of perspiration during dehydration

Raises Blood Pressure by constricting Arterioles

Oxytocin Stimulate contraction of

uterine muscle (smooth muscle)

Initiate milk ejection from the Alveolar Cells into the ducts of the breast in lactating women

Melanocyte-Stimulating Hormone (MSH)

Pars Intermedia (Corticotroph cells)

Melanocytes - Melanin (Darkening of Skin)

Pre-proopiomelanocortin

2o Addision’s Disease (skin darkening)

Estrogen/Progesterone (skin darkening)

Anterior Pituitary Gland

Growth Hormone (Somatotrophin) Prolactin

Tropic Hormones Adenocorticotrophic Hormone (ACTH) Thyroid Stimulating Hormone (TSH) Luteinizing Hormone (LH) Follicle Stimulating Hormone (FSH)

Growth Hormone

Produced by somatotrophs (191AA)

Within target cells increases synthesis of Somatomedins and Insulin-like Growth Factors that act locally or enter bloodstream– common target cells are liver, skeletal muscle, cartilage and

bone– increases cell growth & cell division by increasing their

uptake of amino acids & synthesis of proteins– stimulate lipolysis in adipose so fatty acids used for ATP– retard use of glucose for ATP production so blood glucose

levels remain high enough to supply brain

Abnormal Levels of Growth HormoneHypersecretion of GH During the growth years before

ossification of Epiphyseal plates, causes increase in rate of skeletal growth = Gigantism

After the growth years = Acromegaly-Excess cartilage growth forming new bones.-Enlarged hands, feet, jaws, separation of teeth, -*Soft Tissue (forehead and nose)

Hyposecretion of GH During the growth years, results

in stunted body growth = Pituitary Dwarfism

Prolactin

Hypothalamus regulates lactotroph cells

Primary function is to generate/initiate milk secretion (Lactation)

1. During Pregnancy, high prolactin promote development of breast for milk secretion

2. At Birth of an Infant, suckling reduces levels of hypothalamic inhibition and prolactin levels rise along with milk production

Mammary glands are primed with E/P, Cortisol, GH, T4 and Insulin

Nursing ceases & milk production slows

Abnormal Levels of Prolactin

Hypersecretion of Prolactin

Causes lactation in non-nursing women

Disruption of the menstrual cycle

(Men) can cause impotence

Hyposecretion of Prolactin

Insignificant except in women, who want to nurse feed their babies

ACTH & TSH Hypothalamus releasing

hormones stimulate corticotrophs

Corticotrophs secrete ACTH & MSH

ACTH stimulates cells of the adrenal cortex that produce glucocorticoids

Hypothalamus regulates thyrotroph cells

Thyrotroph cells produce TSH

TSH stimulates the synthesis & secretion of T3 and T4

Metabolic rate stimulated

Luteinizing Hormone Releasing hormones from

hypothalamus stimulate gonadotrophs

Gonadotrophs produce LH In females, LH stimulates

– secretion of estrogen– ovulation of 2nd oocyte from

ovary– formation of corpus luteum– secretion of progesterone

In males, stimulates interstitial cells to secrete testosterone

Follicle Stimulating Hormone Releasing hormone from

hypothalamus controls gonadotrophs

Gonadotrophs release follicle stimulating hormone

FSH functions

– initiates the formation of follicles within the ovary

– stimulates follicle cells to secrete estrogen

– stimulates sperm production in testes

Gonadotrophins