OVERVIEW

Nervous system versus endocrine system

1. Homeostasis – both important in this

2. Nervous system – much more specific

-a. Neurotransmitter – act on effector organ more directly

-b. Synapse – between nerve fiber and effector organ

-c. Action – more immediate

-d. Target cells – muscle (all types); glands; other neurons

3. Endocrine system – more widespread

-a. Hormone – less specific

-b. Action – less immediate; from seconds, hours, to days

-c. Target cells – most cells in body

Endocrine versus exocrine

1. Endocrine gland – secretes hormones into interstitial fluid; then to blood

2. Exocrine gland – secretes substances to ducts which released on surfaces

-a. Organs – located through out body

-b. Tissue – not all endocrine structures are located in endocrine glands

3. Endocrinology – the study of endocrine glands and disorders of these

HORMONES

General

1. Hormone – a mediator molecule released in one part of body effects another part

2. Circulating hormones – released into interstitial fluid, then blood

3. Local hormones – act on self or neighboring cells

-a. Autocrine – acts on cell that produces it

-b. Paracrine – acts on cell in vicinity

The chemistry of hormones

1. Water soluble hormones – amines, peptides, proteins, and eicosanoids

2. Lipid soluble hormones – steroids, thyroid (T3 and T4), and nitric oxide

Secondary messenger systems (water based hormones)

1. Cyclic AMP signaling mechanism

-a. Hormone (amino acid based) – first messenger; activates membrane G protein

-b. G protein – signals by GTP replacing GDP; activates adenylate cyclase

-c. Adenylate cyclase – generates cyclic AMP

-d. Cyclic AMP – second messenger; activates protein kinase

-e. Protein kinase – phosphorylates other proteins; cascading activates; deactivate

-f. Amplification – many cAMP; many protein kinases

2. PIP calcium signaling mechanism

-a. Hormone (amino acid based) – first messenger; activates membrane G protein

-b. G protein – signals by GTP replacing GDP; activates membrane phospholipase

-c. Phospholipase – acts on substrate PIP₂ (phosphatidyl inositol biphosphate)

-d. PIP₂ – diacylglycerol and IP₃ (inositol triphosphate)

-e. Diacylglycerol – activates protein kinases; phosphorylate other proteins

-f. IP₃ – Causes the release of Ca²⁺, third messenger

-g. Ca²⁺ - directly on membrane channel and enzymes or with calmodulin

Lipid soluble hormones

1. Lipid soluble –steroid and thyroid hormones pass through cell membrane to nucleus

2. Nuclear receptor – is bound by the hormone and activated

3. Hormone-receptor complex – now activated seek out specific chromatin protein

4. Specific chromatin protein – turns on a gene

5. Transcription – of a specific mRNA and latter the translation of a protein

6. Chaperonin – when hormone is not present; bind to; inactivate nuclear receptors

Target cell specificity

1. Target cell – the body’s cells which are effected by the hormone

2. Receptor – protein which binds to hormone

3. Up-regulation – response to hormone is production of more receptors

4. Down-regulation – desensitization; hormone causes reduction in receptors

Hormone concentration

1. Concentration – depends on rate of release and inactivation

2. Inactivation – intracellular enzymes; liver enzymes; released by kidney

3. Half life – duration in the blood; less than a minute to 30 minutes

Hormone release

1. Negative feedback mechanism – acts against signal which stimulated its release

2. Endocrine gland stimuli

-a. Humoral stimuli – blood level of ions or nutrients

-b. Neural stimuli – sympathetic release of epinephrine from adrenal medulla

-c. Hormonal stimuli – hypothalamus; pituitary

3. Neural modulation – sympathetic NS (glucose); hypothalamus (water balance)

PITUITARY GLAND (HYPOPHYSIS)

Pituitary gland

1. Location – sella turcica of sphenoid bone

2. Infundibulum – stalk which connects pituitary with the hypothalamus

3. Posterior lobe – nerve fibers; support cells; stores hypothalamic neurohormones

4. Neurohypophysis – infundibulum and posterior lobe

5. Adenohypophysis – anterior lobe; glandular epithelium; no hypothalamic link

6. Hypophyseal portal system – vascular connect hypothalamus and anterior lobe

7. Master gland – regulate activity of many other endocrine glands

8. Hypothalamus – controls pituitary hormones; inhibiting or releasing hormones

Adenohypophyseal hormones

1. Tropic hormones (tropins) – regulate endocrine organs; ACTH; TSH; FSH; LH

2. Growth hormone – anabolic hormone; increase in cell size and division

-a. Insulin-like growth factor – growth of bone and muscle (liver also produces)

-b. Diabetogenic effect – mobilizes lipids; breakdown of glycogen in liver

-c. Gigantism – hypersecretion in child; can reach 8 feet

-d. Acromegaly – hypersecretion in adult; growth of hands, feet, and face

-e. Pituitary dwarfism – hposecretion in child; max height 4 feet; proportional

-f. Progeria – hyposecretion in adult; atrophy; premature aging

3. Adrenocorticotropic hormone – growth of; hormones release from adrenal cortex

-a. Corticotropin (ACTH) – other names

-b. Adrenal cortex hormones – steroid glucocorticoids and androgens, mostly

4. Thyroid stimulating hormone – growth of; hormone release from thyroid gland

-a. Thyrotropin (TSH) – other names

5. Gonadotropins – both FSH and LH; regulate function of gonads

6. Follicle stimulating hormone (FSH) – gamete and hormone production

-a. Females – ovarian follicle maturation; estrogen production

-b. Males – stimulates sperm production

7. Luteinizing hormone (LH) – gamete and hormone production

-a. Females – ovulation; estrogen and progesterone production

-b. Males – testosterone production

8. Prolactin – stimulates milk production in breast

9. Chemical nature – all six are either polypeptides; proteins, or glycoproteins

10. Other hormones – enkephalin, endorphin, and melanocyte stimulating hormone

Posterior pituitary and hypothalamic hormones

1. Oxytocin – uterine contractions and labor; initiates milk ejection

2. Antidiuretic hormone (ADH) – kidney reabsorbs more water

-a. Vasopressin – alternative name; increases blood pressure

-b. Diabetes insipidus – high urine output; decreased ADH; head trauma

3. Chemical nature – each composed of 9 amino acids; very similar

THYROID GLAND

Thyroid gland

1. Location – on trachea inferior to larynx

2. Structure – bilobed, connecting isthmus

3. Follicles – spherical structures make up the thyroid

4. Follicular cells – make up the walls of the follicles

5. Thyroglobin – glycoprotein; in follicle; made by follicular cells

6. Parafollicular cells – penetrate into the connective tissue which surround follicles

-a. Calcitonin – produced by these cells; lowers blood calcium level

Thyroid hormone

1. Thyroid hormone – actually 2; both 2 tyrosine with attached iodine

-a. Thyroxine (T₄) – 4 attached iodine; major form released

-b. Triiodothryronine (T₃) – 3 attached iodine

2. Target organs – all except adult brain, spleen, uterus, itself

3. Calorigenic effect – increases glucose oxidation, metabolic rate, and temperature

4. Other effects – maintains blood pressure; growth bone, nerve, and reproductive

5. Thyroglobin – raw material from which thyroid hormone is made

6. Thyroxine binding protein – most important transport protein

7. Myxedema – adult hyposecretion; edema, lethargy, sluggishness

8. Endemic goiter – if hyposecretion due to lack of iodine; colloid fills follicles

9. Cretinism – congenital hypothyroidism; short, thick tongue, neck; retarded

10. Graves disease – hyperthyroidism; high MR; nervous, sweaty, irregular HB

-a. Autoimmune – antibody like TSH; continual release

-b. Treatment – surgical removal; radioactive iodine

Calcitonin

1. Parafollicular cell (C cells) – produce this polypeptide hormone

2. Bone sparing – inhibits osteoclast from releasing calcium; stimulates uptake

3. Antagonistic – to the action of parathyroid hormone

PARATHYROID GLANDS

Parathyroid glands

1. Location – two pairs; posterior of thyroid; sometimes not

2. Structure – cells arranged in thick branching cords

-a. Chief cells – smaller cells; produce hormones

-b. Oxyphil cells – larger cells; function unclear

Parathyroid hormone

1. Parathormone (PTH) –blood calcium level; clotting, heart, muscle, nerve

2. Chemical nature – protein hormone

3. Target organs – raises blood calcium level several ways

-a. Bone – osteoclast stimulated to release more calcium into blood

-b. Kidneys – absorb more calcium; convert inactive vitamin D3 to calcitrol

-c. Intestine – increased absorption of calcium; enhanced by calcitrol

4. Calcitrol – conversion stimulated by PTH in kidney; for Ca intestinal absorption

ADRENAL (SUPRARENAL) GLAND

Adrenal gland

1. Cortex – outer regions; steroid hormones production; layers

-a. Zona glomeulosa – outer; mineralocorticoids

-b. Zona fasciculata – middle; glucocorticoids

-c. Zona reticularis – inner; gonadocorticoids

2. Medulla – inner region; catecholamine hormones; knot of nervous tissue

-a. Chromaffin cells – modified ganglionic sympathetic neurons; produce hormones

Cortical hormones

1. Mineralocorticoids – regulate electrolyte concentration in extracellular fluid

-a. Aldosterone – most important; causes kidneys to retain sodium and water; ↑BP

-b. Renin-angiotensin – low BP; kidney, renin; angiotensin II; release aldosterone

-c. Electrolytes – low Na, high K; release stimulated

2. Glucocorticoids – body cells; gluconeogenesis; fat and protein catabolism

-a. Cortisol (hydrocortisone) – only important one in humans

-b. Stress – long term stressors promote release

-c. Anti-immune effect – undesirable outcome of stress

-d. Anti-inflammatory effect – use of it in treating inflammatory diseases

-e. ACTH – stress; sympathetic NS; hypothalamus; stimulates release

3. Gonadocorticoids – sex hormones

-a. Androgens – testosterone; maybe onset of puberty; insignificant in adults

4. Cushing’s syndrome – cortisone excess; usually drug induced; tumor, ACTH

-a. Hyperglycemia – gluconeogenesis; steroid diabetes

-b. Protein – in muscle and bone

-c. Buffalo hump – fat redistribution

-d. Infection – may become overwhelming; immune system suppressed

-e. Treatment – remove tumor or stop the drug

5. Addison’s disease – hyposecretion of glucocorticoids and mineralocorticoids

-a. Symptoms – low glucose and sodium; dehydration; weight loss and hypotension

-b. Treatment – hormone replacement

Medullary hormones

1. Catecholamine – synthesized from the amino acid tyrosine

2. Epinephrine – about 80%; stimulator of heart and metabolic activity; clinical use

-a. Clinical use – heart stimulant and bronchial dilator during acute asthma

3. Norepinephrine – vasoconstrictor and blood pressure

4. Stress – flight-or-fight; short term stress; cortisol for long term stress

PANCREAS

Pancreas

1. Location – partially behind stomach

2. Shape – like a tadpole with a head and a tail

3. Acinar cells – exocrine; digestive enzymes; ducted to small intestine

4. Islets – Langerhans or pancreas; cell clusters; scattered; hormone production

-a. Alpha cells – glucagons synthesizing cells

-b. Beta cells – insulin synthesizing cells

Pancreatic hormones

1. Glucagon – 29 amino acid polypeptide; hyperglycemic agent

-a. Glycogenlysis – breakdown of glycogen to glucose

-b. Gluconeogenesis – glucose from lactic acid; fats; amino acids

-c. Liver cells – stimulated to release glucose

-d. Negative feedback – stimulate, low blood glucose; inhibit, high blood glucose

2. Insulin – 52 amino acid protein; hypoglycemic agent; lowers blood glucose

-a. Glucose uptake – by body cells is enhanced by insulin

-b. Enzymatic activity – stimulated for glycogen, fat synthesis; glucose oxidation

-c. Negative feedback – stimulated by high blood glucose

3. Other hormones – somatostatin, ∆cell; pancreatic polypeptide F cells; digestion

Diabetes Mellitus

1. Diabetes mellitus – hyposecretion of inactivity of insulin; high blood glucose

2. Glycosuria – glucose lost in urine

3. Ketone acidosis – can’t use glucose; use lipids; ketones are fatty acid metabolites

-a. Electrolyte imbalance – negative ketones take positive Na + K with them in urine

-b. Nervous system depression – can lead to coma or death if not treated

4. Three cardinal signs

-a. Polyuria – glucose inhibits water reabsorption; dehydration

-b. Polydipsia – excessive thirst; dehydration

-c. Polyphagia – excessive hunger; can’t use glucose in food

5. Type I diabetes mellitus (juvenile) – < 15; β cells destroyed; no insulin activity

-a. Autoimmune – Beta cells destroyed by T cells (mistaken identity of enzyme)

-b. Vascular complications – stroke, heart attack, renal shut down, gangrene, blind

-c. Neural complications – loss of sensation, impaired bladder function, impotence

-d. Insulin – for managing ketoacidosis

6. Type II diabetes mellitus (adult onset) – insulin present; ↓ level or cells can’t use

-a. Insulin resistance – membrane protein may interfere with insulin stimulus

-b. Obesity – over 90%; hormone from adipose tissue may interfere with insulin

-c. Treatment – diet and exercise; drugs to increase insulin, or body’s response to it

7. Hyperinsulinemia – usually insulin overdose; rare islet cell tumor

-a. Symptoms – hypoglycemia; anxiety; in brain ↓glucose, disorientate, coma, death

-b. Treatment – ingest some sugar

OTHER ENDOCRINE ORGANS/STRUCTURES

Gonads

1. Ovaries – produce estrogen and progesterone

-a. Estrogen – sex organ maturation; secondary sex characteristics after puberty

-b. Progesterone – breast development and menstrual cycle (with estrogen)

2. Testes – produce testosterone

-a. Testosterone – develops-maintain, sex organs, 2^nd character; sex drive; sperm

Pineal

1. General – posterior roof of the third ventricle; pine cone shape

2. Melatonin – only major secretory product

3. Diurnal cycle – levels peak at night; lowest around noon

4. Light – duration and intensity; info transmitted to pineal

5. Animals – matting behavior and gonadal size mediated by melatonin

6. Children – maybe antigonadotropic effect; delay puberty

7. Biological clock – melatonin receptors in hypothalamus; sleep, temp., appetite

Thymus

1. General – lobed deep to the sternum

2. Thymosin – peptide hormones; T cell maturation

Other hormone producing structures

1. Atria – atrial natriuretic peptide

2. Gastrointestinal tract – enteroendocrine cells

3. Kidneys – erythropoietin

4. Placenta – estrogen, progesterone, human chorionic gonadotropin

5. Skin – cholecalciferol (Provitamin D)