THE MIGHTY MOLECULES: The Physiology of the

Endocrine System

VIVIEN FE F. FADRILAN-CAMACHO, MD, MPH, FPAFP

Associate Professor

OBJECTIVES

At the end of the course, the students would be able to:

To discuss the basic functions of the endocrine system

To discuss the structural and functional organization of the endocrine system

To explain the physiologic mechanisms of the endocrine system

To discuss the role of specific intrinsic and extrinsic stimuli on the normal physiology of the endocrine system

ENDOCRINE SYSTEM

second great control system of the body

interacts with the nervous system to coordinate

and integrate the activity of body cells

Nervous sytem = via electrochemical impulses; with responses in milliseconds

Endocrine system = via hormones; responses

that occur after a lag period of seconds or

even daysonce initiated, more prolonged

ENDOCRINE SYSTEM: FUNCTIONS

Water balance: controls solute concentration of blood

Uterine contractions and milk release

Growth, metabolism and tissue maturation

Ion regulation

Heart rate and blood pressure regulation

Blood glucose control

Immune system regulation

Reproductive functions control

EXOCRINE VS ENDOCRINE GLAND

Exocrine gland glands with ducts; produce non-hormonal substances membrane surface e.g. sweat and salivary glands

Endocrine glands ductless glands which produce hormones vascular and lymphatic drainage

- Pituitary , thyroid, parathyroid, adrenal, pineal and thymus gland

ENDOCRINE SYSTEM

Hypothalamus neuroendocrine organ

Organs with endocrine and exocrine products:

- pancreas

- ovaries and testes

LOCAL CHEMICAL MESSENGERS Autocrines exert effects on the same cells that

secrete them.

- e.g. prostaglandins smooth muscle cell contraction

Paracrines act on surrounding cells

- e.g. somatostatin inhibits release of insulin release produced by other cells

HORMONE RECEPTORS

Membrane Bound Receptors

Receptor sites on the outer surface of the cell membrane

Interact with large and water-soluble molecules

HORMONE RECEPTORS Membrane Bound Receptor Responses

1. Receptors that directly alter membrane permeability

- opening and closing of ion channels e.g. Ach and Na+ channels in skeletal muscle membranes

2. Receptors that directly alter the activity of enzymes

- or enzyme activities through or activity of cyclic guanosine monophosphae (cGMP)

HORMONE RECEPTORS

3. Receptors and G proteins

- activation of G proteins (complex proteins)

- inactive G protein with , , subunits

- GDP is bound to subunit

- Receptor bindingthe subunit separates from the and . GTP replaces GDP

can open or close channels

activate enzymes

affect gene exporession

HORMONE RECEPTORS

Intracellular receptors

Located in the cytoplasm or nucleus of the cell

Interact with small, lipid intercellular signals

HORMONES

chemical substances

secreted by cells into the extracellular fluids

regulate the metabolic function of other cells in the body

HORMONE ACTIONS

1. Alters plasma membrane permeability or membrane potential, or both, by opening or closing ion channels

2. Stimulates synthesis of proteins or regulatory molecules such as enzymes

3. Activates or deactivates enzymes

4. Induces secretory activity

5. Stimulates mitosis

HORMONES: CHEMICAL STRUCTURE 1. Proteins, peptides and amino acid derivatives

- Bind to membrane-bound receptors with exception to the thyroid hormones which diffuse through membranes and bind to intracellular receptors.

a. Proteins- most hormones of the anterior pituitary glands

b. Peptide hormones hormones of the posterior pituitary gland

c. Amino acid derivatives amino acids that have been chemically modified; hormones of the adrenal medulla

HORMONES: CHEMICAL STRUCTURE 2. Lipid hormones lipid soluble

a. Steroid hormones derived from cholesterol

- hormones produced by the adrenal cortex and gonads

- diffuse across the cell membrane and bind to intracellular receptor molecules

b. Eicosanoids from arachidonic acid

- include prostaglandins, prostacyclins and leukotrienes

- boound to membrane bound receptors that are associated with G proteins

HORMONE RESPONSES

Permissiveness - situation when one hormone cannot exert its full effects without another hormone being present e.g. thyroid hormone on reproductive system

Synergism -occurs where more than one hormone produces the same effects at the target cell and their combined effects are amplified (1+1 =2) e.g. glucagon and epinephrine

Antagonism -one hormone opposes the action of another hormone e.g. insulin and glucagon

NEGATIVE FEEDBACK MECHANISM

ensure a proper level of hormone activity at the target tissue.

After a stimulus causes release of the hormone, products resulting from the action of the hormone tend to suppress its further release.

the hormone has a negative feedback effect to prevent oversecretion of the hormone or overactivity

POSITIVE FEEDBACK MECHANISM

occurs when biological action of the hormone causes additional secretion of the hormone.

luteinizing hormone (LH) release as a result of the stimulatory effect of estrogen on the anterior pituitary before ovulation.

LH ovaries estrogen LH

After LH reaches an appropriate concentration

negative feedback

HORMONE CLEARANCE

(1) metabolic destruction by the tissues

(2) binding with the tissues

(3) excretion by the liver into the bile

(4) excretion by the kidneys into the urine

ENDOCRINE GLAND STIMULI Humoral direct response to changing blood levels

e.g. parathyroid hormone, insulin and aldosterone

Neural stimulated by nerve fibers e.g. catecholamines

Hormonal in response to hormones produced by other endocrine organs e.g. hypothalamic-pituitary axis

Fig 19.1 Endocrine System

HYPOTHALAMUS THE MASTER GLAND

regulates the NS and endocrine system activities by 3 different mechanisms

1) by secreting regulatory hormones that control endocrine cells in the adenohypophysis (anterior lobe) of the pituitary gland:

- Releasing hormones (RH) stimulate production of one or more hormones

- Inhibiting hormones (IH) prevent the synthesis and secretion of specific pituitary hormones

THE MASTER GLAND

2) acts as an endocrine organ, releasing the hormones ADH and oxytocin into the circulation at the neurohypophysis (posterior lobe)

3) contains autonomic centers that have direct neural control over the endocrine cells of the suprarenal medulla sympathetic division is activated medulla hormones

Hypothalamic Control over Endocrine Organs

THE PITUITARY GLAND

Pea on a stalk (infundibulum)

2 lobes: the adenohypophysis (anterior lobe) and the neurohypophysis (posterior lobe)

Hypothalamus regulates secretions of anterior pituitary

Posterior pituitary is an extension of the hypothalamus

Anterior pituitary 9 major hormones that

Regulate body functions

Regulate the secretions of other endocrine glands

Pituitary Gland Structure

Posterior pituitary (neurohypophysis): extension of the nervous system via the infundibulum Secretes neurohormones

Anterior pituitary (adenohypophysis) Consists of three areas with

indistinct boundaries: pars distalis, pars intermedia, pars tuberalis

THE PITUITARY GLAND

Posterior lobe connected to the hypothalamus via the hypothalamic-hypophyseal tract

- paraventricular neurons oxytocin

- supraoptic neurons antidiuretic hormone (ADH)

Anterior lobe

- Hypophyseal portal system vascular connection with the hypothalamus

- where releasing and inhibitory hormones are secreted

Hormones of Posterior Pituitary: ADH

Antidiuretic hormone (ADH). Also called vasopressin.

A. Osmoreceptors (specialized neurons of hypothalamus monitor changes in intercellular osmolality (relative concentrations of electrolytes and water). If the concentration of electrolytes increases or if the concentration of water decreases, then ADH secretion is stimulated.

B. Baroreceptors (specialized neurons found in walls of atria of heart, large veins, carotid arteries, aortic arch) sense changes in blood pressure (BP). If BP decreases, then ADH secretion is stimulated.

Control of ADH Secretion

Control of Oxytocin Secretion

POMC

Propiomelanocortin (POMC)

- prohormone from the anterior pituitary

- source of ACTH, enkephalin, beta-endorphin, lipotropin

- source of melanocyte-stimulating hormone CNS neurotransmitter involved in appetite control

Melanocyte Stimulating Hormone, Endorphins, and Lipotropins

ACTH, MSH, endorphins and lipotropins all derived from the same large precursor molecule when stimulated by CRH

MSH causes melanocytes to produce more melanin

Endorphins act as an analgesic; produced during times of stress.

Lipotropins cause adipose cells to catabolize fat

Adrenocorticotrophic Hormone (ACTH)

CRH from hypothalamus causes release of ACTH from anterior pituitary which

Causes cortisol secretion from the adrenal cortex (a glucocorticoid from the zona fasciculata) against stress

Causes aldosterone secretion from the adrenal cortex (a mineralocorticoid from the zona glomerulosa)

Binds directly to melanocytes of the skin; causes increase in production of melanin.

Growth Hormone (GH or somatotropin)

Stimulates uptake of amino acids; protein synthesis; growth in most tissues.

Stimulates breakdown of fats to be used as an energy source but stimulates synthesis of glycogen: glucose sparing

Promotes bone and cartilage growth

Regulates blood levels of nutrients after a meal and during periods of fasting

Stimulates glucose synthesis by liver

Regulation of GH Secretion

TSH (thyrotropin) and Thyroid Hormones

TRH from hypothalamus causes the release of TSH from anterior pituitary which causes secretion and storage of hormones T3 and T4 from and within the thyroid gland

T3 and T4 inhibit TRH and TSH secretion

LH, FSH, Prolactin

Gonadotropins: glycoprotein hormones that promote growth and function of the gonads

LH and FSH

Both hormones regulate production of gametes and reproductive hormones

Testosterone in males

Estrogen and progesterone in females

GnRH from hypothalamus stimulates LH and FSH secretion

Prolactin: role in milk production

Regulation of secretion: prolactin-releasing hormone (PRH) and prolactin-inhibiting hormones (PIH)

Thyroid Gland Highly vascular Iodine enters follicular cells

by active transport. Only gland that stores hormone.

Histology

Composed of follicles: follicular cells surrounding thyroglobulin/thyroid hormones

Parafollicular cells: between follicles

Follicular cells secrete thyroglobulin into lumen of follicle.

- Iodine and tyrosine necessary for production of T3 and T4.

- Hormones stored here attached to the thyroglobulin then absorbed into follicular cells

- hormones disattached from thyroglobulin and released into circulation.

Parafollicular cells -secrete calcitonin which reduces [Ca2+] in body fluids when Ca levels are elevated.

Thyroid Gland

Thyroid Hormones

Only free thyroxine and T3 can enter cells; bound-thyroxine serves as a reservoir of this hormone

33-40% of T4 converted to T3 in cells T3 more potent Bind with intracellular receptor molecules and

initiate new protein synthesis Normal growth of many tissues dependent on

presence of thyroid hormones.

Effects of T3 and T4

1. Maintain normal rate of metabolism. 2. Increase the rate at which glucose,

fat, and protein are metabolized. 3. Increase the activity of Na+-K+ pump

which increases body temperature. 4. Can alter the number and activity of

mitochondria resulting in greater ATP synthesis and heat production.

5. Normal growth and maturation of bone, hair, teeth, c.t., and nervous tissue require thyroid hormone.

6. Both T3 and T4 play a permissive role for GH

REGULATION OF THYROID HORMONES

Regulation of Calcitonin Secretion

Produced by parafollicular cells

Secretion triggered by high Ca2+ concentration in blood; acts to decrease Ca2+ concentration

Primary target tissue: bone

Decreases osteoclast activity, lengthens life span of osteoblasts.

Parathyroid Glands

Secrete PTH: target tissues are bone, kidneys and intestines.

Increases blood calcium and phosphate levels

Stimulates osteoclasts

Promotes calcium reabsorption by kidneys and PO4 excretion

Increases synthesis of vitamin D absorption of Ca and PO4 by intestines

Regulation depends on calcium levels.

Effects of Parathyroid Hormone

Adrenal Glands Near superior poles of

kidneys; retroperitoneal

Inner medulla; outer cortex

Medulla: Secretes epinephrine and norepinephrine

Adrenal Glands

Cortex: three zones from superficial to deep

Zona glomerulosa

Zona fasciculata

Zona reticularis

Hormones of Adrenal Cortex

Mineralocorticoids: Zona glomerulosa

Aldosterone - rate of sodium reabsorption by kidneys sodium blood levels

Glucocorticoids: Zona fasciculata

Cortisol - fat and protein breakdown, glucose synthesis, inflammatory response

Androgens: Zona reticularis

Weak androgens secreted then converted to testosterone by peripheral tissues. Stimulate pubic and axillary hair growth and sexual drive in females

Adrenal Medulla neurohormones: epinephrine and norepinephrine

Combine with adrenergic membrane-bound receptors

All function through G protein mechanisms

Secretion of hormones prepares body for physical activity

Effects are short-lived; hormones rapidly metabolized

Epinephrine

blood levels of glucose

Fat breakdown in adipose tissue

Causes dilation of blood vessels in skeletal muscles and cardiac muscles.

Epinephrine and norepinephrine HR and force of contraction; cause blood vessels to constrict in skin, kidneys, GI tract, and other viscera

REGULATION OF ADRENAL MEDULLARY SECRETIONS

Stress and the Adrenal Gland

PANCREAS retroperitoneal

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 PANCREAS

Its major target is the liver, where it promotes:

Glycogenolysis the breakdown of glycogen to glucose

Gluconeogenesis synthesis of glucose from lactic acid and noncarbohydrates

Release of glucose to the blood from liver cells

Glucagon

Target tissuesliver, adipose tissue, muscle, and satiety center of hypothalamus

Lowers blood glucose levels

Enhances transport of glucose into body cells

Counters metabolic

activity that would

enhance blood

glucose levels

Insulin

Regulation of Blood Glucose Levels

Results from hyposecretion or hypoactivity of insulin

The three cardinal signs of DM are:

Polyuria huge urine output

Polydipsia excessive thirst

Polyphagia excessive hunger and food consumption

Hyperinsulinism excessive insulin secretion, resulting in hypoglycemia

Diabetes Mellitus (DM)

Diabetes Mellitus (DM)

Hormones of the Reproductive System

Male: Testes

Testosterone

Regulates production of sperm cells and development and maintenance of male reproductive organs and secondary sex characteristics

Inhibin

Inhibits FSH secretion

Hormones of the Reproductive System 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

Thymus Gland, GI Tract, Kidneys

Thymosin-development of the immune system.

GI tract- several hormones regulate digestion and enzyme secretion

Kidneys secrete erythropoietin, which signals the production of red blood cells

Adipose tissue releases leptin, which is involved in the sensation of satiety, and stimulates increased energy expenditure

Hormone-like Substances

Autocrines: chemical signals released by a cell and the substance affects that same cell.

Chemical mediators of inflammation which are modified fatty acids: eicosanoids such as prostaglandins, thromboxanes, prostacyclins, and leukotrienes

Paracrines: chemical signals released into intercellular fluid and affecting nearby cells.

Endorphins and enkephalins modulate sensation of pain

Several growth factors

REFERENCES

Seely, R, Stephens, T, Tate, P. Essentials of Anatomy and Physiology. 6th ed. International Edition 2008. Mc Graw Hill Publishing

Marieb, E., Hoehn, K. Essentials of Human Anatomy and Physiology. 9th ed. Pearson Education Inc. 2011.