Endocrine

Endocrine vs Nervous System

Together, the autonomic nervous and endocrine systems maintain homeostasis

Endocrine System Development

Glands that produce steroid hormones (gonads, adrenal cortex)

• Mesoderm

Glands that produce the amine, peptide, and protein hormones

• Ectoderm - pituitary and pineal gland, adrenal medulla (neuroectoderm)

• Endoderm - thyroid & parathyroid glands, pancreas, and thymus

Endocrine glands

• Ductless glands - primary function is to secrete hormones directly into surrounding fluid

• The same in males and females except for testes (males only) and ovaries (females only)

• Some glands with both endocrine and exocrine function, e.g. pancreas

• Liver-releases hormones, bile into ducts, and non-hormonal products (albumin and blood clotting factors) into blood

• Other tissues, e.g. adipose tissue, also have endocrine functions

Chemical and neural endocrine gland stimuli

Classes of hormones

NOTE: Classes are based on chemical structure

1. Amine hormones

• Synthesised from a single amino acid (tryptophan or tyrosine)

• E.g. melatonin, adrenaline, noradrenaline and dopamine

1. Peptide & protein hormones

• Peptide hormones - multiple amino acids that link to form a short amino acid chain e.g. growth hormone

• Protein hormones - longer polypeptides e.g. insulin

Water-soluble and insoluble in lipids - cannot pass through cell membranes

1. Lipid-derived steroid hormones

• Mostly derived from cholesterol

• E.g. oestrogen and testosterone

Lipid-soluble and non-polar - can diffuse across cell membranes

Intracellular hormone receptors

• Lipid derived hormones readily diffuse through cell membrane and bind to receptors in cytosol

• Thyroid hormones contain benzene rings studded with iodine - also lipid-soluble and can enter the cell

• Receptor-hormone complex enters nucleus and binds to target gene on DNA

• Gene transcription creates mRNA —> translated into desired protein

Cell membrane hormone receptors

• Hydrophilic hormones unable to diffuse through lipid bilaterally

• All amino acid-derived hormones except thyroid hormones

• Do not directly affect transcription of target genes but initiate signalling cascade via a second messenger

• Hormone is first messenger and cAMP most used second messenger

1. Adrenaline binds to beta-adrenergic receptors on plasma membrane.

2. Hormone binding to receptor activates G-protein.

3. G-protein activates adenylyl cyclase.

4. Adenylate cyclase converts ATP to cAMP (second messenger)

5. cAMP activates protein kinases – triggers target cell response (activates

enzymes, stimulates cellular secretion etc.)

6. Phosphodiesterase breaks down cAMP, terminating the signal.

Hypothalamus-pituitary axis

• Command centre of the endocrine system

Hypothalamus

• Structure of diencephalon located anterior and inferior to thalamus

• Both neural and endocrine functions

• Anatomically and functionally related to pituitary gland (or hypophysis)

Pituitary gland (hypophysis)

2-lobed organ suspended from hypothalamus by the infundibulum (or pituitary stalk)

• Posterior pituitary (neurohypophysis) - neural tissue derived from hypothalamic tissue

• Anterior pituitary (adenohypophysis) - glandular tissue developed from primitive digestive tract

Hypothalamic hormones

Anterior pituitary

• Hypothalamic hormones secreted by neurons but enter AP through hypophyseal portal system - can stimulate or inhibit AP hormone secretion

• 7 AP hormones: follicle stimulating hormone (FSH), luteinising hormone (LH), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), prolactin (PRL), beta-endorphin, and growth hormone (GH) - FLATPEG

• FSH, LH, ACTH, and TSH (FLAT) referred to as tropic hormones - ‘turn on or off’ other endocrine glands

Gonadotropins (FSH and LH)

• Regulate function of ovaries and testes

• Release triggered by GnRH during and after puberty

• FSH

  • Stimulated production and maturation of gametes, including ova in women and sperm (sertoli cells) in men

  • Also promotes follicular growth —> release of oestrogen in ovaries

• LH

  • Triggers ovulation and production of oestrogens and progesterone by ovaries

  • Stimulates production of testosterone in Leydig cells of testes

Prolactin

• In females, stimulates breast development and milk production (lactation)

• Normally inhibited by prolactin-inhibiting factor (PIF; dopamine)

• Levels rise during pregnancy in response to prolactin-releasing factors (e.g. oxytocin and TRH) from hypothalamus

• Suckling most powerful stimulus for PRL release

• No negative feedback system - without inhibition by dopamine, prolactin would be secreted indefinitely

Growth hormone (somatotropin)

• GH levels controlled by release of GHRH and GHIH (somatostatin)

• Primary function is anabolic - mediates growth and protein synthesis by triggering the liver and other tissues to produce insulin-like growth factors (IGFs)

• IGFs enhance cellular proliferation and inhibit apoptosis -stimulate cells to increase amino acid uptake from blood for protein synthesis, particularly skeletal muscle and cartilage cells

• Also promotes liplysis and inhibit glucose uptake

Adrenal glands

Adrenocorticotropic hormone (corticotropin)

• ACTH release triggered by corticotropin-releasing hormone (CRH) - naturally occurs in a daily rhythm

• Internal and external factors such as fever, hypoglycemia, and stressors can also trigger the release of CRH, hence ACTH

• Stimulates adrenal cortex to synthesise and release corticosteroid hormones - cortisol, aldosterone and androgens

Adrenal gland hormones - overview

• Wedges of glandular and neuroendocrine tissue adhering to top of kidneys by a fibrous capsule

• Rich blood and nerve supply

Adrenal cortex

HPA axis

• Component of hypothalamic-pituitary-adrenal (HPA) axis

• CRH stimulates ACTH release

• ACTH stimulates adrenal cortex to produce mineralocorticoids, glucocorticoids, and androgens - important for regulation of long-term stress response, blood pressure and blood volume, nutrient uptake and storage, fluid and electrolyte balance, and inflammation

Zona glomerulosa - mineralocorticoids

• Aldosterone - major mineralocorticoid

• Affect body minerals esp Na+ and K+ <— essential for fluid and electrolyte balance

• Important in regulating Na+ and K+ ion concentrations in urine, sweat and saliva

• For example, in response to low Na+, blood pressure or blood volume, aldosterone increases Na+ retention, blood volume and blood pressure

Zona fasciculata - glucocorticoids

• Major role in glucose metabolism - cortisol most important

• Inhibits tissue building while stimulating breakdown of stored nutrients to maintain adequate fuel supplies —>increases blood sugar

• Long-term cortisol - promotes catabolism of glycogen to glucose, stored triglyceride into fatty acids and glycerol, and muscle proteins into amino acids to synthesise additional glucose and ketones for fuel

• Downregulates inflammatory mediators that are important in innate immunity

• Medications containing glucocorticoids - inhibit the inflammatory response

Zona reticularis - androgens

• Small amounts of androgens produced in Zona reticularis

• Converted to testosterone or oestrogens in tissues

• May contribute to sex drive in adult women but function in men is not understood well

• Become main source of oestrogens in post menopausal women as ovarian functions decline

Adrenal medulla

• Modified sympathetic ganglion - an extension of the autonomic nervous system and part of sympathoadrenal system

• Secretes adrenaline and noradrenaline (4 to 1 ratio) into systemic circulation in response to acute, short-term danger or stress - controlled by a neural pathway from hypothalamus

• Flight or fight response: increased blood glucose, heart rate, pulse, and blood pressure; dilation of airways and vasodilation of lungs, brain, heart and skeletal muscle but vasoconstriction in liver, kidneys, GI tract, and skin

• Other effects: dry mouth, loss of appetite, pupil dilation, and loss of peripheral vision

Acute vs Chronic stress response

Thyroid and parathyroid glands

Thyroid-stimulating hormone (thyropsin. TSH)

• Released in response to TRH

• Stimulates normal development and secretory activity of thyroid gland

• Triggers secretion of thyroid hormones by thyroid follicle cells - triiodothyronine (T3) and thyroxine (T4)

• Elevated levels of T3 and T4 in blood trigger a drop in production of TRH and, subsequently, TSH

Thyroid hormones

• Thyroid hormones produced in colloid-containing follicles when mineral iodine atoms attach to the glycoprotein thyroglobulin - diffuse across the follicle cell membrane and enter the bloodstream

• Triiodothyronine (T3), with three iodine and thyroxine (T4) with four iodine atoms

• T4 converted into the more active T3 with a shorter half-life

T3 and T4 are metabolic hormones

• Influence basal metabolic rate

  • Increased nutrient breakdown and use of oxygen to produce ATP

  • Increased glucose oxidation. With high-level of heat as a byproduct—>raised body temperature

• Essential for foetal and childhood tissue development and growth, especially nervous system

• Complex interrelationship with reproductive hormones - deficiencies can influence libido, fertility, and other aspects of reproductive function

• Increase body’s sensitivity to adrenaline and noradrenaline by upregulation of receptors in blood vessels —> excessive T3 and T4 accelerate heart rate, strengthen heartbeat, and raise blood pressure

Thyroid hormone - Calcitonin

• Produced by parafollicular cells in tissue between thyroid follicles

• Released in response to a rise in blood calcium levels - appears to decrease blood calcium concentrations by:

  • Inhibiting osteoclast activity

  • Increasing osteoblast activity

  • Decreasing calcium absorption in intestines

  • Increasing calcium loss in the urine

• Functions usually not significant in maintaining calcium homeostasis - important of calcitonin is not entirely understood

Parathyroid glands

• Embedded in the posterior surface of the thyroid gland

• Chief cells produce and secret parathyroid hormone (PTH), in response to low blood calcium levels

• PTH

  • Exerts direct effects on bone and kidney and indirect effects on intestine through calcitriol (metabolite of vitamin D3 produced in kidneys)

• PTH + calcitriol

  • Stimulates osteoclastic bone resorption and inhibit osteoblasts

  • Increase intestinal calcium and renal calcium reabsorption

• Negative feedback loop - rising blood calcium levels inhibit further release of PTH

POSTERIOR PITUITARY

Posterior pituitary

• Extension of hypothalamic neurons

• Cell bodies rest in hypothalamus, but axons descend as hypothalamic-hypophyseal tract to posterior pituitary

• Does not produce hormones but stores and secretes hormones produced by hypothalamus

• Oxytocin from paraventricular nuclei and ADH from supraoptic nuclei

• Signals from hypothalamic neurons initiate hormone release into blood

Antidiuretic hormone (vasopressin. ADH)

• Released in response to increase in plasma osmolarity (ie. Water loss or reduced intake)

• Promotes water reabsorption from forming urine in kidneys - conserves water

• Can also cause vasoconstriction (hence vasopressin) and raise blood pressure in high concentrations

• Negative feedback loop -as blood osmolarity decreases, hypothalamic osmoreceptors prompt decreased ADH secretion

• Drugs, e.g. alcohol, can affect ADH secretion

Oxytocin

• Stimulates uterine contractions and dilation of the cervix

• Continually released throughout childbirth through a positive feedback mechanism

• Continues to play a role in maternal and newborn health - necessary for milk ejection reflex (“let-down”) and contributes to parent-newborn bonding (attachment)

• Also thought to be involved in feelings of love and closeness, as well as sexual response

Peripheral nervous system overview

Endocrine pancreas

Cells and secretions

• Pancreatic islets (previously islets of langerhans) secrete glucagon, insulin, somatostatin, and pancreatic polypeptide (PP)

• Alpha cells - release glucagon in response to low blood glucose

• Beta cells - release insulin in response to high blood glucose

• Delta cells - release somatostatin which inhibits glucagon and insulin release

• PP cells - release PP which plays a role in appetite and regulation of pancreatic secretions

Regulation of blood glucose

• Release triggered by gastrointestinal tract hormones in the presence of food a dfuether stimulated by rising blood glucose levels

• Primary targets are skeletal muscle and adipose tissue cells - require insulin for glucose uptake

• No insulin receptors on red blood cells and cells of brain, liver, kidneys, and lining of the small intestine do not require insulin for glucose uptake

• Appears to trigger multiple biochemical reactions that result in rapid movement of glucose transporter vesicles to cell membrane where they facilitate glucose into cell

Processes moderated by insulin

• Facilitates uptake of glucose from the blood and stimulates glycolysis, lowering blood glucose levels

• Stimulates glycogenesiss in liver and skeletal muscle and inhibits glycogenolysis and glucogenesis

• Also promotes triglyceride and protein synthesis

Gluconeogenesis - the process of making glucose from its own breakdown products or from the breakdown products of lipids (fats) or proteins

Glycogenolysis - liver converts its stores of glycogen back into glucose and release glucose into blood

Glycolysis - the metabolic pathway that converts glucose into private in the cytosol

Glycogenesis - the process of glycogen synthesis, in which glucose molecules are added to chains of glycogen for storage; opposite of glycogenolysis

Regulation of blood glucose

• Release triggered by falling blood glucose levels sensed by receptors in pancreas

• Stimulates gluconeogenesis, glycogenolysis, and the release of glucose into the circulation, raising blood glucose levels

Other glands and organs with endocrine function

Pineal gland

• Functions not entirely clear

• Pinealocytes produce and secrete the amine hormone melatonin (derived from serotonin)

• Melatonin secretion dependent on light level

• Daylight: production is inhibited - low blood melatonin levels promote wakefulness

• Declining light levels: production increases, boosting blood levels and causing drowsiness

Kidneys

• Play a role in regulating blood calcium levels via calcitriol production from vitamin D3, released in response to PTH secretion (PTH)

• Produce erythropoietin (EPO) in response to low oxygen levels - stimulates production of red blood cells in bone marrow, thereby increasing oxygen delivery to tissues

Adipose tissue

• Leptin : produces feeling of satiety after a meal, thereby reducing appetite - also appears to trigger increasing deposition of cortical bone

• Adiponectin : appears to reduce insulin resistance and protect blood vessels from inflammation and atherosclerosis - lower in obese people and rise following weight loss