Endocrinology Flashcards
What is a hormone?
Chemical messengers released from one tissue, carried in the circulation that produces a specific, receptor-mediated change in another tissue
Name four major actions of hormones
Development: proliferation, growth, differentiation, organogenesis
Metabolism: Energy storage, metabolic rate, temperature
Reproduction: Sexual maturation, pregnancy, lactation
Fluid homeostasis: water balance, electrolye balance, blood volume and blood pressure
What are the characteristics of peptide hormones and catecholamines?
Rapid changes in plasma concentration
Short plasma half-life (secs to mins)
Receptors on the cell membrane
Act via second messengers to change enzyme activity
Promote secretion from granules/vesicles.
Effects are rapid
What are the effects of steroid hormones and thyroid hormones
Slow fluctuations in plasma concentration
Long plasma half life (mins to days)
Intracellular receptors
Passage is direct and rapid (related to secretion rate)
Alters gene transcription, Stimulates protein synthesis
Effects are slow (take hours to days)
Describe the synthesis of protein and peptide hormones
Peptide-derinved hormones are synthesised and stored in advance of need.
Most peptide hormones are synthesised from larger precursors (preprohormone)
After the gene is transcribed, the peptide is synthesised with a prepeptide or signal peptide at the N-term that directs it to the RER.
The prepeptide is cleaved off in the RER to form the prohormone.
This then undergoes post-translational procesessing by golgi apparatus and is proteolytically cleaved to yield the active hormone which is packaged into secretory vesicles.
Describe the synthesis of steroid hormones
Steroid hormones are synthesised and secreted on demand.
Cholesterol is the starting material for the synthesis of steroid hormones which is stored in the form of cholesterol esters within lipid droplets inside the cell.
Cholesterol esters are hydrolysed by enzymes to generate free cholesterol that enters the mitochondria.
Inside the mitochondria, cholesterol molecules bind to cholestrol cleaveage enzymes on the mitochondrial membrane where it is remodelled into pregnolone.
Pregnolone leaves the mitochondria and enters the SER where it is remodelled by enzymes into the relevant steroid hormone.
The final steroid hormone can then diffuse out of the cell.
Name three hormones that are derived from tyrosine
Dopamine
Norepinephrine
Epinephrine
Thyroid hormone
Name five hormones that are derived from cholesterol
Progesterone
Oestradiol
Testosterone
Aldosterone
Cortisol
What are the endocrine actions of cortisol (8 points)
Facilitates foetal maturation
Maintains cardiac output (decreases endothelial permeability and increases arteriolar tone)
Inhibits the inflammatory immune response
Increases GRF and water clearance in the kidneys
Stimulates the release of amino acids from muscles (decreases muscle mass)
Increases blood glucose: stimulates gluconeogenesis, inhibits glucose uptake by GLUT4
Inhibits osteoblast function, (decreases new bone formation, increases bone resorption)
Inhibits fibroblast proliferation and collegen synthesis
Hormones produced by the posterior pituatury gland
Oxytocin
Vasopressin
Hormones produced by the anterior pituatory gland
Adrenocorticotrophic hormone (ACTH): control secretion of adrenal steroids
Thyroid stimulating hormone:controls release of thyroid hormones. Controls growth, development and thermogenesis
Growth hormone: antagonises effects of insulin, promotes growth of bone, soft tissue and viscera
FSH
LH
control sexual differentiation (ovaries and testes), behaviour and fertility
Prolactin: promotes mammary growth, development and lactation
Hormones produced by the adrenal cortex
glucocorticoids (cortisol)
mineralocorticoids (aldosterone)
sex hormones (testosterone
Hormones released by the hypothalamus
Corticotrophin releasing hormone (ACTH release)
Thyrotrophin releasing hormone (TSH and prolactin release)
Growth hormone releasing hormone ( GH release)
Gonadotrophin releasing hormone (LH and FSH release)
Somatostatin/GHIH (inhibits GH and TSH release)
Dopamine (inhibits prolactin synthesis and release)
Hormones are released fromthe hypothalamus in response to neural inputs from other areas of the CNS
What are the four types of hormonal control?
Endocrine
Neuroendocrine
Paracrine
Autocrine
How do hormone receptors help to regulate endocrine responses?
Hormone effects are mediated by specific high affinity receptors and can therefore bind the hormone when levels in the circulation are low
Receptors are often inactivated or destroyed after binding its hormone. This decreases the responsiveness of the target cell to the hormone. Reactivation or upregulation re-sensitises the target cell.
Name 3 techniques that can be used to measure hormone levels
Radioimmunoassay
ELISA
Bioassay
Where are catecholamines synthesised?
In the adrenal medulla
How do endocrine disorders arise?
Can be caused due to excess or deficient secretion of a hormone, or a failure to respond to a hormone due to the absence or malfunction of a receptor
Name 4 hormones secreted from the adrenal gland and state where they are secreted from
Adrenal cortex:
Aldosterone (mineralocorticoid)
Cortisol (glucocorticoid)
DHEA (androgens)
Medulla:
Catecholamines
Name five tissues with endocrine function and the hormones they secrete
Kidney: erythopoietin
Heart: Atrial Naturetic Peptide
Gut: gastrin, secretin
Adipocytes: Leptin
Placenta: Lactogen
Describe the mechanism of action of steroid hormones
Steroid hormones are lipophyllic and can easily cross the plasma membrane
The hormone binds to an intracullular receptor which activtes it.
The receptor-hormone complex translocates to the nucleus and binds to response elements in the DNA.
Transcription factors are activated
Transcription of specific genes in enhanced, therefore increasing synthesis of specific proteins
Describe the action of vasopressin
Vasopressin release is stimulated by an increase in plasma [solute] and a decrease in blood volume.
Vasopressin binds to receptors on the collecting ducts of the kidneys and promotes water absorption. This reduces plasma [solute] and conserves blood volume.
The increase in blood volume and fall in plasma [solute] inhibits release of vasopressin
AVP release can also be stimulated by pain, trauma, low pO2, other hormones
Describe the action of oxytocin
Oxytocin secretion is stimulated during parturition and lactation.
Breast feeding stimulates sensory nerves which cause burst of oxytocin to be released into the blood stream. This stimulates contraction cells in the lactating mammary gland, aiding milk ejection
During parturition, cervical dilation stimulates stretch receptors in the cervix, stimulating oxytocin-secreting neurons. Oxytocin release stimulates the contraction of smooth muscle cells in the uterus during labout, aiding delivery.
Describe the main actions of growth hormone
Growth promoting: Stimulates IGF-1 which acts in an autocrine or paracrine way to stimulate cell division, resulting in growth. Stimulates chondrocyte and osteoblast differentiation resulting in bone growth. Increases protein synthesis in muscle
Lipolytic: Stimulates breakdown of triglycerides from fat stores
Diabetogenic: Inhibits glucose uptake by muscle and adipose tissue and increaases gluconeogenesis in the liver. Inhibits the action of insulin on glucose and lipid metabolism in muscle and adipose tissue
Effects of growth hormone disorder
Deficiency: Pituitary dwarfism (decreased rate of body growth)
Excess:
Acromegaly/ gigantism
Weight gain, increased size of hands and feet, joint pain, tiredness, polyuria/polydipsia
Describe how thyroid hormone secretion is regulated
Thyrotrophin releasing hormone (TRH) is produced by neurons in the hypothalamus.
TRH binds to receptors on the plasma membrane of thyrotrophic cells in the anterior pituitary gland which promotes the release of TSH into the blood.
TSH increases the rate of thyroid hormone secretion.
The thyroid hormones then exert negative feedback effects on the hypothalamus and the pituitary by inhibiting TRH synthesis and release from the hypothalamus and reducing the sensitivity of thyrotroph cells to TRH and TSH synthesis in the pituitary.
How is ACTH produced?
ACTH is synthesised in the anterior pituitary as part of a lerger prohormone POMC (proopiomelanocortin) which is enzymatically cleaved and processed to produce several peptides.
The major products are ACTH which stimulates hormone production in the adrenal cortex, and beta-lipotrophin which has a mild effect on lipid breakdown.
Lesser products include melanocyte stimulating hormones (MSH) which cause pigmentation of the skin and beta-endorphins which control hunger, thirst and reduce fertility.
Explain how an excess of glucocorticoids can lead to Cushings syndrome
Cushings disease is caused prolonged exposure to excessively high levels of glucocorticoids (mainly cortisol).
This can be ACTH-dependent, where the anterior pituitary is secreting excess ACTH that stimulates the adrenal glands to make excess cortisol, or ACTH-independent where the adrenal cortex secretes excess cortisol.
The most common clinical symptom of Cushings is weight gain and central obesity. This is because cortisol causes the breakdown of skeletal muscle, increases gluconeogenesis and lipolysis. This causes hyperglycaema and therefore insulin release which promotes the deposition of fat centrally, in the spine (causing back pain) and in the cheeks which gives the moon-like facial appearance.
Cortisol is also involved in controlling wakefulness, therfore excess levels leads to insomnia.
Name five symptoms of Addison’s disease
Weight loss
Anorexia
Weakness
Impotence
Fever
Caused by destruction of the adrenal cortex, results in low glucocorticoids and mineralocorticoids.
Describe the regulation of endocrine glands in males
Endocrine glands in males: hypothalamus, anterior pituitary, testes
The hypothalamus processes information from the external and internal environment and releases GnRH
GnRH stimulates the release of LH and FSH in the anterior pituitary gland.
LH binds to Leydig cells and stimulate the production of testosterone. FSH binds to Sertoli cells and stimulates spermatogenesis.
Testosterone sends inhibitory signals to the hypothalamus and anterior pituitary to stop hormone production. The testes also release hormones which inhibit FSH and LH
Describe the regulation of endocrine glands in females
The hypothalamus produces GnRH which controls the secretion of LH and FSH from the anterior pituitary
FSH stimulates the growth of ovarian follicles and oestrogen in the menstrual cycle while LH induces ovulation and regulates progesterone secretion from the corpus luteum.
Ovarian steroids inhibit the release of LH and FSH
Describe the action of aldosterone
Aldosterone is a mineralocorticoid.
Its principal site of action is on the distal and collecting tubules of the nephron where it promotes Na+ retention and enhances K+ excretion during the formation of urine.
Increased Na+ retention results in the retention of water in the extracellular fluid by osmosis, therefore increasing blood pressure.
Aldosterone production is stimulated by ACTH and angiotensin II
