1
Q
Endocrine system is responsible for?
A
Responsible for the control of a large number of homeostatic variables as well as the regulation of our development, growth and reproduction.
2
Q
Interaction between the nervous system and endocrine system in controlling many body functions.
A
- Nervous system functions are very fast and highly specific forms of communication
- Endocrine system which mediates communication at a much slower rate, but produces much more widespread effects
- Mediated by chemical messengers (hormones) released by secretory organs (endocrine glands) into the blood stream.
- These hormones travel through the systemic circuit and bind to receptors associated with their target tissues.
- Binding of the hormone to the target tissue receptors mediates the effects
3
Q
How do drugs impact the endocrine system?
A
- A number of drugs used to treat ailments such as hypertension and cancer either mimic or block the actions of hormones
4
Q
Study of endocrine system?
A
Endocrinology
5
Q
What is a hormone?
A
Chemical messengers (hormones) released by secretory organs (endocrine glands) into the blood stream.
6
Q
What is a tropic hormone?
A
- Do not produce direct effects on other physiological systems
- Regulates the release of hormones by other endocrine organs and/or to control the development and growth of these endocrine organs
7
Q
What is an endocrine gland?
A
Organs that release hormones
8
Q
What is an endocrine cell?
A
A cell that secretes a hormone - dependent on endocrine organ
9
Q
Where the major endocrine glands are located and the hormones that they secrete?
A
10
Q
What is the pituitary gland?
A
- known as the hypophysis is found on the base of the brain in a small depression in the sphenoid bone
- highly vascular and is physically attached to the hypothalamus by a stalk-like structure known as the infundibulum
- Master endocrine gland – regulates growth and function of a number of other endocrine glands
-Divided into 2 regions: anterior pituitary (adenohypophysis) and posterior pituitary (neurohypophysis). Secretion of 8 hormones
11
Q
What hormones does the anterior pituitary gland secrete?
A
12
Q
What hormones does the posterior pituitary gland secrete?
A
13
Q
What is the parathyroid gland?
A
- 4 discrete structures located on the posterior of the thyroid gland
- secrete parathyroid hormone (PTH) responsible for calcium homeostasis
- acts on bone, the digestive tract and the kidneys to increase circulating calcium ion concentrations in blood
14
Q
What is the thyroid gland?
A
- bilobed structure located on the anterior and lateral surfaces of the trachea just inferior to the larynx.
- largest pure endocrine gland
- secretes calcitonin = antagonistic to PTH - decreases blood Ca2+ levels
- thyroid hormone (T4 and T3) = stimulates glucose oxidation and metabolic rate
15
Q
What is the thymus gland?
A
- located in thoracic cavity adjacent to the sternum
- reaches is maximum size during childhood and gradually declines during adulthood.
- secretes a number of peptide hormones responsible for the development of the immune system
16
Q
What is the adrenal gland?
A
- pair on endocrine organs located on top of the kidneys (known as suprarenal glands)
- consists of 2 regions
- adrenal cortex (outer shell) - secretes over 20 steroid hormones (corticosteroids)
- adrenal medulla (core) - contains chromaffin cells - secretes adrenaline and noradrenaline. Considered to be sympathetic postganglionic neurones (innervated by sympathetic preganglionic neurones)
17
Q
What is the pancreas?
A
- mixed endocrine/exocrine gland adjacent to stomach
- secretes 2 major hormones - homeostatic control of blood glucose
- insulin - b-cells of pancreas = reduces blood glucose levels by promoting uptake by muscle and fat cells
- glucagon - a-cells and acts antagonistically to insulin. Released by hypoglycaemia - increases blood glucose by breakdown of glycogen and release of glucose from liver
18
Q
What are testis?
A
- contains large number of Leydig (interstitial) cells responsible for production of testosterone
- development of male secondary sex characteristics and stimulation of spermatogenesis
19
Q
What other organs have cells that have endocrine functions?
A
Brain, digestive tract, heart and kidneys
19
Q
How do hormones interact with carrier proteins?
A
- Release of hormone into circulation, some hormones bind to carrier proteins and transported in the blood as complexes.
- The hormone-carrier protein complex is inactive since the hormone cannot bind to its receptors
- Hormone must dissociate from the carrier protein in order to produce effects on the target tissue
20
Q
Why is hormone interaction with carrier proteins useful?
A
- Provide a readily available supply of the hormone within the circulation
- Act as a buffer and smooth out the spikes in hormone secretion that are characteristic of some endocrine organs
- Make the hormone less likely to be metabolised (broken-down) by enzymes in the blood, liver and kidneys
21
Q
Length of actions for hormones and carrier proteins?
A
- Hormones bound to carrier proteins tend to be involved in long-term actions such as growth.
- Hormones involved in shorter duration actions such as adrenaline tend to be found free in the circulation
22
Q
What are peptide hormones made up of?
A
- Chains of amino acids - size varies depending on hormone
i.e. thyrotropin-releasing hormone (3 amino acids) vs growth hormone (191 amino acids)
23
Q
Where are peptide hormones synthesised and how are they released?
A
- Rough endoplasmic reticulum of appropriate endocrine glands
- Golgi apparatus for processing
- Hormones packaged in secretory vesicles where they are stored until released
- After exposed to the right trigger, the hormone is secreted by exocytosis into adjacent capillaries
24
How do peptide hormones bind?
- Peptide hormones circulate in free state
- Enter into the extracellular space and bind to specific receptors associated with their target cells
- Receptors are membrane-spanning proteins with the binding site for the peptide hormone on the extracellular side of the membrane
- Binding triggers conformational change of the receptor which triggers a response in the target cell
25
How do peptide hormone receptors produce responses in target cells?
- Peptide hormones bind to a membrane-associated receptor (R)
- Activates an intracellular G-protein (GP)
- Activates the enzyme adenylate cyclase (AC)
- Production of the second-messenger (cAMP)
- Diffuses through the cytoplasm and mediates the intracellular effects of the hormone
26
Molecular pathway responsible for synthesis of noradrenaline in most catecholamine secreting cells?
- Cytoplasm of catecholamine secreting cells, tyrosine is enzymatically converted to dihydroxyphenylalanine (L-DOPA) and then dopamine (DA).
- Dopamine is transported into membrane-bound secretory vesicles
- Enzymes required for its conversion to noradrenaline are located here
- Noradrenaline is stored until released by exocytosis.
27
Release of anime hormones?
- Release amine hormones circulate in a free state
- Enter into extracellular space
- Bind to adrenergic receptors present on their target issues
27
Subclass of adrenergic receptors in cardiac muscle?
28
How is this different (noradrenaline/catecholamine) in the adrenal medulla?
- Noradrenaline is transported back into cytoplasm
- Acted upon by an enzyme only found here
- Result of this enzymatic reaction is adrenaline
- Transported back into the secretory vesicles for storage and subsequent secretion
28
Subclass of adrenergic receptors in cardiac muscle, bronchial smooth muscle and digestive system?
29
How are steroid hormones (cortisol and aldosterone) synthesised?
- Derivatives of cholesterol and include hormones: cortisol and aldosterone
- Secreted by adrenal cortex and the various sex hormones secreted by the gonads
- 80% of cholesterol from dietary intake and taken up by cells through receptor-mediated endocytosis and the remainder is synthesised
- Inside the cell cholesterol is released from the secretory vesicle and converted to pregnenolone (precursor to steroid hormone) within the cytoplasm
- Different cells process pregnenolone into various steroid hormones (cortisol, aldosterone, sex hormones), hormones are synthesised de novo in response to appropriate stimulus and leave cell by simple diffusion due to their lipid solubility
30
How do steroid hormones produce responses in target cells?
- Hormone-receptor complex diffuses into the nucleus of target cells
- Binds to DNA sequences of specific genes and mediates effects of the steroid hormone in the cell
- Hormone-receptor complex binding to DNA up-regulates the transcription of the specific genes
- Synthesis of the appropriate proteins to mediate the response in these target tissues
31
What is meant by a circadian rhythm and give an example of or hormone that is under this type of regulation
- Cyclical changes in secretion of hormones: cortisol, growth hormone and melatonin
- Circulating levels of these hormones oscillate with a frequency close to 24hrs they are described as having a circadian rhythm
- Light/dark exposure, suggests cells of endocrine glands themselves have a molecular clock that up- and down-regulates the secretion of these hormones in a cyclical fashion
32
Negative feedback + hormone control systems --> illustrate
- Hormone exerts an inhibitory influence on cells that produce
- Conc. of hormone increases then negative feedback increases
- Amount of hormone produced declines and vice versa results in restoration of status quo
Example - thyroid stimulating hormone (TSH)
- T3 and T4 are important hormones in the maintenance of a variety of homeostatic variables including BMR.
- Both T3 and T4 have an inhibitory effect on the anterior pituitary gland and through this negative feedback mechanism regulates the circulating levels of TSH
32
What is meant by negative feedback?
- Stable circulating levels of hormones are required to maintain homeostasis in most common form of control = negative feedback
33
What is meant by positive feedback?
- Hormone exerts an excitatory effect on the cells that secrete the hormone.
- Less common than negative feedback
Example: excitatory effect that oestrogen has on gonadotropin secretion during the ovulatory phase of the menstrual cycle
34
Describe the macroscopic and cellular processes involved in growth.
- Longitudinal growth – lengthening of somatic tissues such as bone, muscle and tendons
- Radial growth – increase in diameter of these somatic tissues as well as other organs
- Hyperplasia – increase in number of cells
- Hypertrophy – increase in size of cells
35
Where does growth hormone comes from, pattern of secretion and consequences of its association with growth hormone-binding protein.
- Synthesised and secreted by cells known as somatotrophs in the anterior pituitary gland
- Pulsatile pattern – highest levels begin 60mins after sleep and continue (70%)
- Free state in plasma, remainder is bound to growth hormone-binding protein --> increases half life of the hormone and reduces rate of enzymatic degradation
36
What are the metabolic effects of growth hormone?
- Skeletal muscle – GH acts directly on skeletal muscle fibres to increase amino acid uptake and protein synthesis --> increased muscle mass
- Adipose tissue – GH stimulates lipolysis which involves breakdown of stored triglycerides and release of fatty acids and glycerol in blood --> reduces fat deposits in body
- GH enhances lean body mass
37
Describe the growth-promoting effects of growth hormone and explain how these are mediated by the insulin-like growth factors.
- GH stimulate synthesis/secretion of 2 peptide hormones stimulate growth in various tissues: insulin-like growth factor I & II (IGF-I & IGF-II)
- IGFs synthesised by liver and secreted into systemic = form complexes with one of six IGF-binding proteins
- Stimulates protein synthesis and cell proliferation of chondrocytes near ends of growing bone resulting in longitudinal growth
- Stimulating protein synthesis, hyperplasia and hypertrophy in a wide variety of tissues resulting in tissue growth and consequently increased organ size (radial growth)
38
Where does growth hormone-releasing hormone and somatostatin come from and how they regulate the secretion of growth hormone?
- Growth hormone-releasing hormone (GHRH – 43 amino acid peptide) secreted by neurones in the arcuate nucleus of the hypothalamus
- GHRH binds to membrane-associated receptors on somatotrophs and stimulates release of GH (anterior pituitary)
- 2 forms of somatostatin but is 14 amino acid peptide (SS-14) involved in control of GH secretion
- Synthesised and released from neurones in periventricular region in hypothalamus and reaches anterior pituitary through hypophyseal portal vessels
- SS-14 binds to membrane-associated receptor on somatotrophs produces inhibition of GH release – local capillaries in anterior pituitary glands are known as hypophyseal portal vessels
39
How does growth hormone secretion get regulated by growth hormone as well as somatostatin, ghrelin and insulin-like growth factor I.
- GH has an inhibitory effect on somatotrophs and on the arcuate nucleus neurones of the hypothalamus. The net effect of this is a direct inhibition of GH secretion and an indirect inhibition through the reduction in the stimulatory effect of GHRH
- IGF-I that is released from the liver in response to GH also has an inhibitory effect on GH secretion in 3 different ways
o A direct inhibitory effect on GH secretion by the somatotrophs of the pituitary gland
o An indirect inhibition of GH secretion by inhibition of GHRH release from the hypothalamus
o An indirect inhibition of GH by stimulation of SS-14 secretion by the hypothalamus
- 28-amino acid peptide = ghrelin. Synthesised by the epithelial cells lining the stomach and is though to be partly responsible for the sensation of hunger but is also a potent stimulator for GH secretions
40
Consequences of growth hormone deficiency and hypersecretion
- Dwarfism = growth hormone deficiency
- Gigantism = hypersecretion
- Acromegaly = increase of GH during adulthood – hypertrophy of bones, skeletal muscle etc
41
Explain the clinical uses for recombinant growth hormone
- Growth hormone extracted from humans post mortem treat children with growth retardation. More recently unlimited supply of recombinant growth hormone
o Role of GH in normal aging remains poorly understood, but given acute (metabolic) effects of GH it has been suggested that some of the physical consequences of aging might be reversed with recombinant growth hormone therapy
Med Phys
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