Week 6 Part 2 Flashcards
Synthesis of Peptide Hormones: Overview
Same synthesis as for any other peptide
Transcription, translation
Mrna is translated into peptide sequence
Peptide Hormone Synthesis: Post- Translational Modifications
To become fully functional, many proteins require further processing after translation
Peptide hormones subject to variety of such modifications, e.g.
Preprohormones
-inactive precursor from single gene -cleaved → active components
Chopped into specific fragments which are the hormones/ active products
e.g. pre-pro-opiomelanocortin (POMC)
Dimerisation
-subunits from different genes -combine → active product
Active hormones are 2 hormones, alpha with specific beta combine = hormone
e.g. LH, FSH, TSH
Secretion of Steroid Hormones
Steroids are lipophilic (relative soluble in fat, insoluble in water)
• They are synthesised from cellular lipid stores only when required and not stored as active hormone within cells
• Diffuse across the cell membrane into the blood, so no active secretory mechanism, water soluble molecules can’t do
• Once in the blood, they are mostly transported bound to plasma proteins
Hormone Signalling: Introduction to Receptors
Inter-cellular signalling molecules regulate target cells by binding to specific proteins, called receptors
Respond to specific signals -> response
• Hormone receptors are thus essential for the function of the endocrine system
• Many types of receptor, but can be loosely categorised as
– membrane-bound receptors (expressed on the external plasma membrane)
– intracellular receptors, found within target cell
Membrane-Bound Receptors
Mechanism of action for hydrophilic peptide and amine hormones
• Proteins present in the plasma membrane
• Many different types, but all have 3 basic domains
– Extracellular (binds hormone) specific shape so specific hormone to bind to it
– Transmembrane
– Intracellular (often necessary for effects in target cell, e.g. change in enzyme activity)
Extracellular binds causes a 3d change in intracellular
Typically, responses are rapid,
- change in membrane permeability
(e.g. adrenaline)
- change in enzyme activity
(e.g. insulin)
Short duration effect
Intracellular Receptors
Mechanism of action for steroids and thyroid hormones
• Stimulate gene expression → delayed & prolonged response
Hormone Diffuse across membrane to receptors within in the cytoplasm or the nucleus
Hormone receptor complex > nucleus = transcription factor and changes rate of transcription, changing rate of protein synthesis
Which makes the process slower
Hypothalamic Regulation of the Anterior Pituitary Gland
Control centre for endocrine
Pituitary is an important ‘gateway’ between central and peripheral endocrine organs
• Many (5) major endocrine
cell types
– each has regulatory control from hypothalamus via inhibitory and/or releasing factors
• Many pituitary hormones regulate secondary (“down- stream” endocrine organs)
Anterior pituitary > at the front
Posterior > back
Hypothalamic Regulation of the Anterior Pituitary Gland
Indirect signaling pathway
Pituitary portal system transfers releasing and inhibitory hormones from hypothalamus to anterior pituitary
Median eminence sits at the base of hypothalamus, special blood supply
Portal system, first capillary bed > 2nd capillary bed (surrounds anterior pituitary)
Hormones released from hypothalamus into median eminence > portal > 2nd capillary bed into anterior pituitary
Hypothalamic Regulation of the Posterior Pituitary Gland
Direct secretion
Cell bodies, make hormones travel down axons to nerve terminals directly into systemic blood supply
Feedback Loops
Negative
Imposes “brake” on system
• Important for homeostasis
• Common in physiology
(inc. endocrinology)
Target cell Inhibits endocrine cell
Positive
Amplifies original signal
• By itself, not compatible with
homeostasis
• Rare but useful in certain circumstances
when a large response is required
• Requires cut-off mechanism> shut down positive feedback to returns to normal homeostatic control
High amount of hormones for physiological response
Negative Feedback Loops: Hypothalamo-Pituitary Regulation
General Model
(anterior pituitary loops)
Positive Feedback Loops: The “LH Surge”
Oestrogen usually inhibits LH secretion via negative feedback
• But, oestrogen surge occurs around day 12 of cycle
• High oestrogen drives change from -ve to +ve feedback
• +ve feedback causes LH surge, which induces ovulation
• After ovulation, drop in oestrogen conc causes resumption of -ve feedback and thus LH/FSH secretion falls
