MacDonald Flashcards
What speed do hormones act?
Slow response, low acting
Where are hormones produced?
In endocrine glands
What are the 3 classes of hormones?
Peptides
Amines
Steriods
How do nuclear hormones cross the plasma membrane?
Hydrophobic diffusion
Carrier proteins
What type of targets do steroid hormones have?
Nuclear
What are the types of steroid hormones?
Glucocorticoids Mineralocorticoids Androgens Oestrogens Progestogenss
What are the 2 vague classifications of steriod hormones?
Adrenal
Gonadal
Where are the corticosteroids produced?
Adrenal cortex
How are the corticosteroids synthesised?
Dervived from cholesterol via pregenelone by the action of dehydroxylation and dehydrogenation
Which enzymes catalyse the synthesis of corticosteroids?
Cytochrome P450s
How is the synthesis of corticosteroids stimulated?
7 releasing hormones from hypothalamus
anterior pituitary releases secondary hormone
Adrenal cortex stimulated
How many hormones do the adrenal glands produce?
36
What are the 3 regions of the adrenal cortex?
Glomerulosa
Fasiculata
Reticularis
What class of steroid hormones does the glomerulosa region of the adrenal cortex produce?
mineralocorticoids
What region of the adrenal cortex is responsible for the synthesis of glucocorticoids?
Fasiculata
What region of the adrenal cortex is responsible for the synthesis of androgens?
reticularis
What is the main glucocorticoid?
Cortisol
What is the main mineralocorticoid?
Aldosterone
What are the main roles of cortisol?
Increase gluconeogenesis
Mobilisation of fatty acids and amino acids
Inhibition of glucose uptake in muscle and adipose tissues
How is cortisol released?
Stress Hypothalamus CRH Anterior Pituitary ATCH Adrenal gland
What are the gonadal steroids?
testosterone
oestrogen
Where is testosterone synthesised?
Leydig cells in the testes
Transported by ABP
Activated in Sertolli cells
What is the active form of testosterone?
dihydrotestosterone
What is the synthesis pathway for steroid hormones?
Cholesterol
Pregenelone
Progesterone
Mineralo/Gluco/testosterone
How is oestrogen derived?
From testosterone using aromatase enzyme in ovaries
Where is oestrogen produced in post-menopausal women?
Adrenal glands
Where is progesterone produced?
in corpus luteum
What effects does progesterone have?
Changes in luteral phase of menstrual cycle
A differentiation factor for mammary glands
What is the releasing hormone for oestrogen?
FSH
What is LH the releasing hormone for?
Progesterone and testosterone
What is angiotensin the releasing hormone for?
Aldosterone
How are most steroid hormones found?
Inactive forms bound to carrier proteins in blood
What structure do steroid receptors have?
Modular transcription factors with
(N)variable-zinc finger-ligand binding
What are orphan receptors?
No identified ligand
How does ligand binding activate receptors?
Conformational change exposes DBD
Are steroid receptors ubiquitous?
No, none in yeast or plants
What are the 2 classes of steroid receptors?
Classical class 1 RXR class 2
How are Class 1 receptors activated?
Release from HSP
Migration to nucleus
Homodimer TFs bind to inverted repeat
What are examples of Class 1 receptors?
Androgens,
Corticosteroids
Progesterone
Where are RXR receptors found?
Constitutively bound to DNA
How do RXR receptors bind DNA?
As heterodimers with another TF
How are nuclear hormones degraded?
Steroids are hydroxylated/sulphated/glycosylated in liver
Thyroids are de-iodinated
How can steroid signalling be switched off?
Absence of stimulus
ligand degradation
Receptor dissociation
How is secretion of cortisol regulated?
Negative feednack to CRH and ATCH
What is Addisons disease?
Absence of cortisol
What are the symptoms of lack of cortisol?
hypotension, darkening of skin, weight loss vomiting salt cravings cardiac arrest in crisis
How is addisons disease caused?
Autoimmune attack of adrenal glands
Infectious disease
What does aldosterone do?
Raise blood volume and blood pressure,
Raise Na levels
Reduce K levels
Where does aldosterone act?
In kidney and small intestine
How is aldosterone produced?
Kidney senses stimuli
releases renin
Conversion of angiotensinogen (liver) to angiotensin 1
angiotensin 1 converted to angiotensin II by ACE
Angiotensin releases aldosterone
What receptors does aldosterone act on?
glucocorticoid receptors
How are cells selective for aldosterone over cortisol?
Cortisol converted to cortisone by 11-β-hydroxysteroid dehydrogenase
cortisone lower affinity
What gene does aldosterone transcribe?
Na/K pump
What is aldosteroidism also known as?
Conn’s syndrome
What symtpoms does Conn’s syndrome have?
High Na/K pumps
Hypertension and cardiac failure
Depletion of K and muscle weakness
What is congenital adrenal hyperplasia?
Absence of mineralocorticoids and overexpression of androgens
What is congenital adrenal hyperplasia caused by?
90% caused by mutations of 21-hydrolase enzyme
What symptoms does congenital adrenal hyperplasia have?
Lack of corticosteroids
Salt wasting
Mis-development of the sex characteristics
Where does oestrogen bind?
ERE receptor in promoters of 600 genes
AP1 /ER independant pathways
What function does oestrogen have?
Proliferation of cells
How common is ER receptor overexpression?
70% of breast, ovarian, colon, prostate, endometrial cancers
How does ER overexpression cause cancer?
Increased cell proliferation has more spontaneous DNA mutations
Metabolism of oestrogen produces genotoxic waste
What ER receptor is found in differentiated tissue?
ERα
What does tamoxifen do?
Neutralise ER overexpression
treats anvoluntary infertility
treats gynecomastia
Where is vitamin D synthesised?
Skin, Kidney and liver
How is Vitamin D transported?
carrier proteins in blood
How is vitamin D synthesis stimulated?
By PT gland sensing low Ca
Secretes PTH
Stimulates liver activation of D3
What effects does vitamin D have on a cell?
Binds RXR-LXR receptors
Mobilisation of Ca from bone
Kidney Ca retention
Intestinal calbindin Ca channel
What do Vitamin D deficiencies cause?
Ricketts/osteomalacia
How can vitamin D deficiencies be caused?
Hereditary mutations of receptor
Lack of sunlight
Kidney/Liver disease
Poor dietary intake of precursor
