Overview of the endocrine system
- consists of endocrine glands that secretes hormones into the blood
- hormones exert physiological effects at very low concentrations, at the right time, in the right amount
Functions - metabolism
- regulation of the internal environment
- reproduction
- growth and development
Half life
The amount of time required to reduce the concentration of hormone in the circulation by one half- indicator of how long a hormone is active in the body
Hormone degradation - enzymes in liver in kidney (excreted in Nike or urine)
- extracellular enzymes degrade hormones bound to receptors
- endocytosis of receptor- hormone complex
- intracellular enzymes
- important to break down after exerted effects to prevent damage. Kidney and livers are major breakdown site.
Chemical classification of hormones
Peptide and protein hormone
- from 3 aa to larger proteins and glycoproteins
- growth hormone, insulin
- much smaller than plasma proteins and can occur in urine
Steroid hormone
- derived from cholesterol and made in only a few organs
- placenta produces estrogen and progesterone during pregnancy
- adrenal cortex produced cortisol and aldosterone
- gonads produce testosterone, estrogen and progesterone
Amino acid derived/ amine hormones
- created from tryptophan or tyrosine
- melatonin is synthesised from tryptophan in the pineal gland
- thyroid hormone is synthesised from tyrosine in the thyroid gland
- catecholamines (include epinephrine and norepinephrine) are synthesised from tyrosine in the adrenal medulla
Hormone transport in the blood
Water soluble
- peptide and catecholamine
- transported dissolved in plasma
- some use carrier protein
- short half life, several minutes
Lipid soluble
- steroid and thyroid hormones
- circulate bound to plasma carrier proteins
- only unbound hormone is biologically active
- the carriers obey the law of mass action and release hormone so the rate of unbound to blind hormone in plasma remains constant
- longer half life, the carrier proteins protect from enzymatic degradation and thus extend half life, can be over an hour
Cellular mechanism of action of peptide hormones
- lipophobic, unable to enter target cell
- the catcholamines are neurohormones that bind to cell membrane receptors the way that peptide hormones do
- activate cell membrane receptors
- the hormone receptor complex initiates the cellular response by means of a signal transduction system
- the response of cells is usually rapid because second messenger systems modify existing proteins
- responses include: opening and closing membrane channels and modulating metabolic enzymes or transport proteins
Cellular mechanism of action of steroid hormones
- most hydrophobic steroids are bound to plasma protein carriers. Only unbound hormones can diffuse into the target cell.
- steroid hormone receptors are in the cytoplasm or nucleus.
- some steroid hormones also bind to membrane receptors that use second messenger systems to create rapid cellular responses.
- the receptor hormone complex binds to DNA and activates or represses one or more genes.
- activated genes create new mRNA that moves back to the cytoplasm
- translation produces new proteins for cell processes.
- thyroid hormones behave like steroid hormones
Control of hormone release
- stimulus- usually ions, nutrients, hormones, neurohormones, circadian rhythms
- sensor
- input signal
- signal integration- in the simplest reflect endocrine cells act as sensor and integrating centre; endocrine cell directly senses a stimulus and responds by secreting a hormone.
- output signal (hormone)
- target
- response (in the simplest reflex, the response usually serves as negative feedback signal that turns off the reflex)
Hormone interactions
Synergism: when two or more hormones interact at their targets so that the combination yields a result that is greater than additive.
Permissiveness- one hormone cannot fully exert its effect unless a second hormone is present, even though the second hormone has no apparent action.
Antagonism: two molecules work against each other. One diminishing the effectiveness of the other. Functional antagonists have opposing physiological actions.
Hormone pathologies
Excess- due to hypersecretion, can be caused by benign and cancerous rumours of endocrine glands
Deficiency- due to hyposecretion, most common cause is atrophy of the gland due to disease process
Abnormal responsiveness of target cell- target tissue has reduced response to hormone, may be due to downregulation of receptors to reduce responsiveness to excess hormone. Some pathologies are due to absent or malfunctioning receptors, or problems with signal transduction pathways.
The pituitary gland
+ posterior pituitary gland
Sits in a protected pocket in bind connected to the brain by a thin stalk called infundibulum.
Posterior pituitary is an extension of the neural tissue.
In the posterior pituitary:
- neurohormone is made and packaged in cell body of Neuron
- vesicles are transported down the cell
- vesicles containing neurohormone are stored in posterior pituitary
- neurohormones are released into blood via vein.
Two hormones: oxytocin, controlled by pos feedback, controls ejection of milk during breastfeeding, contraction during labour- vasopressin controlled by neg feedback, acts on kidney to regulate water balance
Anterior pituitary
Anterior pituitary is a true endocrine gland of epithelial origin.
- neurons synthesising trophic neurohormones release them into capillaries of the portal system
- portal veins carry the trophic neurohormones directly to the anterior pituitary, where they act on endocrine cells.
- endocrine cells release their peptide hormones into the second set of capillaries for distribution to the rest of the body.
Include prolactin for milk production, growth hormone from growth and metabolism, TSH for hormone synthesis and secretion, ACTH for synthesis of cortisol, and gonadotropin for function of ovaries and tested
Hypothalamic releasing and inhibiting hormones
Influence secretion of anterior pituitary hormones
APH hormones
Thyroid stimulating hormone, stimulated by thyrotopin releasing hormone (TRH)
Adrenocorticotrophic hormone (ACTH), stimulated by corticotropin releasing hormone (CRH)
Growth hormones, stimulated by GHRH and inhibited by growth hormone inhibiting hormone
Feedback loops in the hypothalamic anterior pituitary pathway
A pituitary hormone feed back to decrease hormone secretion by the hypothalamus
Dominant form of feedback where the hormone secreted by the peripheral endocrine gland suppresses secretion of its anterior pituitary and hypothalamic hormones.
The growth hormone pathway
Hypothalamic GHRH stimulates growth hormone secretion which acts directly on many body tissues but also influences liver production of insulin- like growth factors (IGFs) which also regulate growth.
Influenced by circadian rhythm, circulating nutrients, stress and other hormones
- promote protein synthesis, fat breakdown and hepatic glucose output
- increases cartilage growth, blood glucose and bone and tissue growth
Growth hormone pathologies
- dwarfism (hormone deficiency)
- gigantism (over secretion)
- acromegaly - over secretion after bone growth plates have closed.
Insulin
Secreted by beta cells in the islets of langerhans in the pancreas.
stimulated by:
- distension of GI tract wall after meal, parasympathetic output
- presence of carbohydrates in lumen- particularly 100mg/dL plasma glucose
- nutrient digestion and absorption, increased plasma aas and increased plasma glucose
In skeletal muscle:
Has effects on transport activity in adipose tissue and resting skeletal muscle. Insulin also has effects on metabolism.
In fed state, insulin binds to receptor, signal transduction cascade, exocytosis, glucose enters cells
In liver:
Glucose diffuses into cell via GLUT2 transporter (not insulin dependent) that is always in the membrane. When intracellular glucose is low, glucose will diffuse into the liver cell; insulin keeps glucose low by increasing glucose use and storage
Glucagon
Primary function- prevent hypoglycaemia
Major target for glucagon is liver
Alters existing enzymes and stimulates synthesis of new enzymes to increase plasma glucose through glycogenolysis, gluconeogenesis and ketones.
Fasted state:
Glucose diffuses out of liver cell via GLUT2 transported that are always in membrane. When intracellular glucose is high, glucose will diffuse out of the liver cell; glucagon keeps glucose high by increasing glycogenolysis and gluconeogenesis. Enhanced secretion when plasma is 65-70mg/dL
Thyroid hormone
Thyroid follicles found in thyroid gland. Follicular cells secrete thyroid hormone.
Colloid is a glycoprotein which produced thyroid hormone.
TSH stimulates release of hormone as well as growth of follicular cells.
Thyroid hormone targets most cells of body/ activates nuclear receptors
Systemic effects:
Increase oxygen consumption
Interact with other hormones to modulate carbohydrate, fat and protein metabolism
Needed for full expression of growth hormone in children; essential for normal growth and development, especially the nervous system
Hyperthyroidism
Hyperexcitable reflexes and psychological disturbances
Muscle weakness- increased protein catabolism
Warm sweaty skin and heat intolerance- increased oxygen consumption and metabolic heat production
Rapid heart beat and increased force of contraction- upregulation of beta adrenergic receptors in the heart
Eg. Graves’ disease or low iodine
Hypothyroidism
Bradycardia- slow heart rate
Brittle nails, thinking hair, dry think skin- decreased protein synthesis
Intolerant to the cold- decreased oxygen consumption and metabolic heat production
Slowed reflexes, slow speech and thought processes, fatigue- nervous system change in adults
Cretinism (in infancy) marked by decreased mental capacity- poorly developed nervous system
Cortisol
Is a glucocorticoid secreted from middle region of adrenal cortex.
Corticotropin released hormone stimulates the release of adrenocorticotropic hormone from the anterior pituitary gland.
Targets most tissues of the body, activates intracellular receptors.
Has a permissive effect on glucagon and catecholamines, secretion usually peaks in the morning and diminishes during the night, stress increases secretion.
Made from cholesterol
Actions of cortisol
Promotes gluconeogenesis in the liver increasing blood glucose concentrations
Enhances lipolysis making fatty acids available for energy for peripheral tissues; glycerol is used for gluconeogenesis
Causes breakdown of skeletal muscle proteins to provide substrate (amino acids) for gluconeogenesis
Suppresses the immune system by preventing cytokines release and antibody production; inhibits the inflammatory response by decreasing leukocyte mobility and migration.
Catabolic in bone; decreases calcium absorption at intestine and increases excretion at kidneys
Influences brain function
Causes and pathologies of cortisol hypersecretion
Pituitary rumour that autonomously secreted ACTH
Adrenal tumour that autonomously secreted cortisol
Hypercortisolism (cushings shndrome)
Mood alteration- difficulty with learning and memory due to altered CNS
Hyperglycaemia due to excess gluconeogenesis
Tissue wasting- muscle protein breakdown and lipolysis; bone catabolism
Extra fat in the trunk and face- may be due to increased appetite and food intake
Hyposecretion of cortisol (Addison’s disease)
Usually caused by immune destruction of adrenal cortex
