Review of Endocrinology Flashcards
what is a hormone
are signalling molecules that modulate the activity of a target tissue
are synthesized by particular endocrine glands and then are secreted in the bloodstream to be carried to a target tissue some distance away
Mechanisms of Hormone Delivery
- Classical Endocrine Signalling = endo cell –> blood –> target cell
- neuroendocrine signalling = neuro-endo cell –> blood –> target cell
- autocrine regulation= hormone –> diffuses through interstitial fluid –> target cell nearby
- paracrine regulation = hormone from cell A –> diffuses through interstitial fluid –> hormone reaches cell B
Synthesis of Peptides
Peptides: short sequence of amino acids that are joined by peptide bonds
substrate: amino acids
Sequence of Events
- transcription of peptide gene – > peptide mRNA
- translation of peptide mRNA –> peptide
- post-translational modifications
Synthesis of Glycoproteins
Glycoproteins: polypeptides containing carbohydrate moieties covalently bonded to the alpha and beta subunits
substrate: amino acids, carbohydrates
sequence of events
- transcription of polypeptide genes
- translation of polypeptide mRNAs
- post-translational modifications –> glycosylation
2 subunits:
- alpha is common among hormones
- beta is unique for each hormone
Synthesis of steroids
steroids: lipids, derived form cholesterol, contain common molecular nucleus: cyclopentanoperhydrophenanthrene
substrate: cholesterol
Sequence of Events
cholesterol–> pregnenolone –> progesterone –> testosterone –> estradiol
cell machinery needed
- enzymes
- transcription
- translation
- post-translational modifications
Synthesis of Eicosanoids
Eicosanoids: lipids, derived from arachidonic acid
Substrate: arachidonic acids (PUFA)
Sequence of Events
membrane phospholipids –> tissue specific isomerases –> end product
cell machinery needed
- enzymes
- transcription
- translation
- post-translational modifications
Secretion: pattern and duration
Episodic: hormone released in bursts, varying in duration and quantity , when predictable, it is also called pulsatile secretion
Basal: hormone remains low and fluctuates with amplitude
sustained: steady secretion for extended time
regulation by feedback
affect synthesis or secretion of hormones
represents a fine-tuned control of hormone secretion
feedback is the communication between different tissue/cells
there are positive and negative feedbacks
- positive –> induces greater secretion
- negative –> inhibits secretion
there are interactions between feedback loops of different hormones
- progesterone levels have a dominant effect over estradiol on GnRH stimulation
transport to the target tissue- what needs a carrier in plasma and what doesn’t ?
glycoproteins and peptides are soluble in plasma
steroids and eicosanoids need carrier proteins for transport
Cell Membrane Receptor
hormone specific extracellular domain –> trans membrane domain changes shape after binding the ligand –> activated G-proteins create downstream signaling that affects protein synthesis or activity of existing proteins and the biology of the cell
fast response
- protein hormones, steroid hormones, eicosanoids
Nuclear Receptor
lipophilic steroid hormones can cross the membrane and go to nucleus
hormone-receptor complex acts as transcription factor
complex binds to a consensus sequence - response element
slow response
- steroid hormones
- eicosanoids
receptor density
varies with expression of the gene and protein
- cell type and presence of stimulators or repressors
- it can be up and or down regulated by (hormone) or duration of exposure
receptor hormone affinity
increase interactions between H and R –> increase receptor affinity –> increase biological response
agonists or analogs: similar structure and action as native hormone
- bind receptors with similar or greater biological activity
Antagonists: interferes with native hormone action
- bind to receptor with greater affinity than native hormone
- promotes weaker biological activity than the native hormone
Clearance: hormone half-life
rate of hormone clearance determines the hormone half-life
- binding proteins (protection)
- glycosylation (protection)
- metabolism
longer half-life –> increase biological activity for a longer time
rapid hormone turnover is often essential for biological action
protein hormone metabolism
De-glycosylation or Denaturation
- deglycosylated hormones bind to liver cells then are internalized and degraded in the cytoplasm
- amino acids are recycled
denatured in plasma and lose activity
