Flashcards in Endocrinology - Overview of hormones Deck (16):
What are hormones?
Hormones are chemical messengers that are transported via the bloodstream and produce their physiological effects distant to their site of synthesis or release.
How are protein and peptide hormones synthesised?
Peptide hormones are synthesised from preprohormones. This occurs in the endoplasmic reticulum and is directed by specific mRNA.
Signal peptides are cleaved from the preprohormone producing a prohormone. This is then transported to the golgi apparatus. Additional peptide sequences are cleaved in the golgi to form the hormone which is packaged into secretory granules for later release.
What a steroid hormones synthesised from?
Steroid hormones are derivatives of cholesterol.
What are amine hormones synthesised from?
Amine hormones (e.g. thyroid hormones, adrenaline, noradrenaline) are synthesised from tyrosine.
How are hormones regulated by negative feedback?
This is the most common form of feedback regulating hormone secretion.
It is self limiting; a hormone has a biologic action that, directly or indirectly, inhibits further secretion of the hormone. Insulin, for example, is secreted by the beta cells of the pancreatic islets in response to high plasma glucose. It turn, insulin promotes cellular uptake of glucose which lowers the plasma concentration and inhibits further hormone release.
How are hormones regulated by positive feedback? Give an example
Positive feedback is rare, and is self reinforcing. A hormone has a biologic action that, directly or indirectly, causes more secretion of the hormone.
For example, the surge in LH that occurs before ovulation is the result of positive feedback of oestrogen on the anterior pituitary. LH then acts on the ovaries and causes more secretion of oestrogen.
What are G proteins?
G proteins are guanosine triphosphate (GTP) binding proteins that couple hormones to effector (2nd messenger) molecules.
They have intrinsic GTPase activity and contain 3 subunits (alpha, beta and gamma). The alpha subunit can either bind GDP or GTP. When the alpha subunit binds GDP the G protein is inactive. When GTP is bound the G protein is active.
They are used in either the cAMP (adenylate cyclase) or IP3 effector systems. Inhibitory or stimulatory activity is determined by the alpha subunits.
Describe the adenylate cyclase mechanism?
A hormone (e.g. ACTH, LH, FSH, TSH etc) binds to a G protein coupled receptor on the cell surface. GDP is replaced by the alpha subunit for GTP and the G protein is active. If the G protein is inhibitory it inhibits that activity of adenylate cyclase. If the G protein is stimulatory it activates adenylate cyclase.
Adenylate cyclase catalyses the conversion of ATP to cAMP. This in turn activates protein kinase A which phosphorylates specific proteins producing physiological actions.
How is cAMP regulated?
cAMP is degraded by phosphodiesterase which is inhibited by caffeine. Therefore phosphodiesterase inhibitors augment the physiological actions of cAMP.
What is the IP3 mechanism?
Hormones bind to a cell surface G protein coupled receptor and via a Gq protein activate phospholipase C.
Phospholipase C liberates diacylglycerol (DAG) and IP3 from membrane lipids. IP3 mobilises intracellular calcium from the endoplasmic reticulum. Together, Ca++ and DAG activate protein kinase C which phosphorylates proteins and causes specific physiological effects.
Hormones that use this pathway include TRH, GnRH, GHRH, and ADH.
What are catalytic receptor mechanisms?
Hormones bind to extracellular receptors that have, or are associated with, enzymatic activity on the intracellular side of the membrane. Examples include, guanylyl cyclase and receptor tyrosine kinases.
What hormones are associated with the enzyme guanylyl cyclase?
1) Atrial natriuretic peptide (ANP) acts through receptor guanylyl cyclase, where the extracellular side of the receptor binds ANP and the intracellular side of the receptor has guanylyl cyclase activity. Activation of guanylyl cyclase converts GTP to cyclic GMP which is the second messenger.
2) Nitrix oxide (NO) acts through cytosolic guanylyl cyclase. Activation of guanylyl cyclase converts GTP to cyclic GMP which is the second messenger.
What are tyrosine kinases?
Hormones bind to extracellular receptors that have, or are associated with, tyrosine kinase activity. When activated, tyrosine kinases phosphorylate tyrosine moieties on proteins, leading to the hormones physiologic actions.
What are receptor tyrosine kinases and what hormones bind to them?
Hormones bind to extracellular side of the receptor. The intracellular side of the receptor has intrinsic tyrosine kinase activity. There are different types of receptor tyrosine kinase.
One type of receptor tyrosine kinase is a monomer (e.g. receptor for nerve growth factor). Binding of hormone or ligand causes dimerisation of the receptor, activation of intrinsic tyrosine kinase and phosphorylation of tyrosine residues.
Another type of receptor tyrosine kinase is a dimer (e.g. receptors for insulin and insulin like growth factor). Binding of hormone activates intrinsic tyrosine kinase leading to phosphorylation of tyrosine moeities.
What is a tyrosine kinase-associated receptor?
This is the mechanism of growth hormone. Growth hormone binds to the extracellular portion of the receptor. The intracellular side of the receptor does NOT have intrinsic tyrosine kinase activity but is non covalently associated with tyrosine kinase (e.g. Janus family of receptor associated tyrosine kinases).
Binding of the hormone causes dimerisation of the receptor and activation of tyrosine kinase in the associated protein (e.g. JAK). Targets of JAK include signal transducers and activators of transcription (STAT) which causes transcription of new mRNAs and new protein synthesis.