Endocrine - Growth and Metabolism

Pituitary Gland

Intermediate Lobe

• alpha & beta

• MSH stimulates melanophores

Posterior Lobe

• vasopressin (antidirectic hormoren, ADH)

• oxytocin

Posterior Pituitary Hormones

• oxytocin & vasopressin

• small peptides ~ 8-9 amino acids

• synthesized in the hypothalamus

• release is not under control of hypothalamus

Oxytocin

• increases uterine contraction

• elicits milk ejection from mammary glands

Vasopressin

• released in response to bp

• acts to maintain blood osmolarity & volume

• increase water reabsorption in collecting ducts of kidney

• binds to V2 receptors in kidneys

• also binds to v1 receptors in smooth muscle (vasoconstriction)

thyroid gland % hormones

releases two types of hormones

• T3 trilodothryonine (59% iodine)

• T4 thyroxine (65% iodine)

important in growth/development, energy metabolism regulation, body temp maintenance.

• calcitonin

important in regulating calcium metabolism

T3 & T4

• stored in thyroglobulin protein, constitutes majority of thyroid follicular colloid

• active form: L-isomers

• t3 is more potent than t4

• T3 transported to target; bind to receptors:

  • nuclear: modify gene transcription

  • cytoplasmic: initiates cell signaling

thyroid hormone receptors

nuclear receptor

• modulates gene transcription; slower activity

  • TRa and TRb form homodimers or heterodimers w/ transcription factors, retinoid x receptors

  • activate gene trans

cytoplasmic binding protein

• modulates intracellular signaling: faster activity

Thyroid Gland

consists of folllicles (vesicles) made up of thyroid follicular cells

thryoglobulin associated with inner surface of follicle

Thyroglobulin (TG)

synthesized at colloid/cell interface

T3 &T4 synthesized and stored as amino acid residues in TG

Thyroid Hormone Synthesis

TSH stimulates uptake of iodide by thyroid follicular cells: oxidized to iodine

Iodination of tyrosine in TG forms mono-iodinated (MIT) and di-iodinated (DIT) tyrosine

coupling of MIT & DIT and storage in TG

Proteolysis and secretion of thyroid hormones T3 & T4

Deiodinated T4 converts to T3

Growth/Development

Thyroid hormone (TH) regulates optimal g & d throughout the body

• stimulates protein synthesis critical for nervous, skeletal, and reproductive tissues

Cretinism

due to iodine deficiency; failure of thyroid to develop during infancy; dwarfism, mental retardation, pale skin, slow heart rate, low body temp

calorigneic effect

TH increases resting or basal metabolic rate:

• modulates key enzymes including Na+/K+ atpase and other rmetablic enzymes

• most sensitive tissues: heart, skeletal muscles, liver and kidney

• TH increases body temp

• alterations in body temp feedback to regulate TH production

cardiovascular effect

increases heart rate and force of contraction

increases cardiac output

mechanism:

• direct effect: binding to TH receptors in the heart; not just response to increased basal metabolism

• indirect: increased number of beta receptors in heart

metabolic effects

• stimulate metabolism of cholesterol to bile acids

• increased binding to LDL by liver

• increased carbohydrate metabolism

• increased glucose uptake

adrenal glands short term response to stress

• increased heart rate

• increased bp

• liver converts glycogen to glucose and releases into blood

• dilation of bronchioles

• changes in blood flow patterns leading to:

  • increased alertness

  • decreased digestive system activity

  • reduced urine output

• increased metabolic rate

adrenal glands long term response to stress

• retention of Na and water by kidneys

• increased blood volume and pressure

• proteins and fats converted to glucose or broken down for energy

• increased blood sugar

• suppression of immune sys.

glucocorticoids: zona fasiculata

• synthesized in response to ACTH

• regulate carbohydrate metabolism

  • cortisol (hydrocorticortisone)

mineralocorticoids: zona glomerulosa

• synthesized in response to angiotensin II and K+

• regulate electrolyte balance (salt retention)

  • aldosterone

adrenal androgens: zona reticularis

• weak androgens - contribute to normal maturation

• synthesized in response to ACTH

  • dehydroepiandrosterone (DHEA)

Mineralocorticoids and Glucocorticoids Physiologic Effects

• influence carbohydrate, protein, and lipid metabolism

• water and electrolyte balance

• cardiovascular function

• kidney

• skeletal muscle

• nervous system

• allow body to respond to external stimuli

• influence most cells and tissues

• major metabolic consequence due to direct actions on targets or to homeostatic responses by insulin and glucagon

glucocorticoids

• major endogenous hormone

  • cortisol

• not stored

• rate synthesis = rate release

• synthesized rhythmically

  • controlled by irregular pulses of ACTH

  • influenced by light and stress

  • major pulses early morning and after meals

Cortisol

• originates from adrenal cortex

• transported by corticosteroid-binding globulin made in liver

• half life: 60-90 min

• CRH (HT) → ACTH (Ant. Pit.) → cortisol (AC)

• intracellular receptor

• tissue response

  • increases plasma [gluc.]

  • decrease immune activity

  • permissive for glucagon and catecholamines

• cell response

  • increase gluconeogenesis and glycogenolysis

  • increase protein catabolism

  • blocks cytokine production by immune cells

• molecular response

  • initiates transcription, translation, and new protein syn.

• feedback regulation

  • negative FB to ant. pit. and HT

Effects of cortisol

physiologic effects depends on:

• environment

• activity of the individual

• activity of the hormones

metabolic effects

• increase nutrient availability by raising blood gluc, amino acid, and triglyceride lvls

  • goal is to maintain energy homeostasis during stress response

• increases blood gluc bu antagonizing insulin action

  • promotes gluconeogenesis

• increase muscle protein breakdown releasing amino acids which are used by liver as fuels for gluconeogensis

• potentiates growth hormone action

  • increases lipolysis

• causes negative calcium balance

anti-inflammatory and immunosuppressive actions of cortisol

affects all formed blood elements

• increases RBC and hemoglobin content

• increases polymorphonuclear leukocytes

• lympholytic: kills B and T cells within 6 hours

• inhibits macrophage functioning: blocks production of inflammatory mediators

  • reversible

mineralocorticoids

regulate electrolyte and water balance

• aldosterone - most important mineralocorticoids in humans

• increase reabsorption Na+ from distal tubes and collecting ducts of kidney into plasma

• increase excretion K+ and H+ → increase in fluid volume

regulation of aldosterone release by angiotensin II

blood volume decreases → aldosterone release increases

decrease in blood volume, pressure and perfusion → kidney → renin protease → renin substrate (alpha-2 globulin) -(cleavage)→ angiotensin I -(ACE)→ angiotensin II → aldosterone -(Na+ permeability)→ kidney