Prolactin & the Laboratory Perspective Flashcards
What glands and tissues can produce prolactin?
- Anterior pituitary
- Mammary glands
- CNS
- Immnue system
- Uterus
How is prolactin controlled (generally)?
It’s inhibited by dopamine (hypothalamic regulation)
How does dopamine inhibit prolactin (mechanism)?
Dopamine binds to dopamine D2 receptors on the surface of lactotrophs.
This diminishes intracellular cAMP, consequently decreasing prolactin secretion
Might help thinking of dopamine as a squatter. Dopamine sticks to prolactin’s home (lactotrophs), stealing its resources (cAMP), so prolactin doesn’t get made
In general terms, what can cause hyperprolactinemia?
Anything that disturbs the delivery of dopamine to the AP or signal transduction
What are the effects of PRL excess in males and females?
-In females, amenorrhea (caused by PRL inhibiting GnRH)
-In males, headaches and decreased libido (decreased libido due to decreased spermatogenesis due to PRL affecting Hypothalamus-Pituitary reproductive axis)
-Galactorrhea in non-breastfeeding females or males
Apparently the galactorrhea discharge tastes really bitter and rancid, go out and confirm this for me
What role does PRL play and how is it controlled during pregnancy?
-Significant role in breast development
-Increases during pregancy and stims growth/development of mammary tissue in preparation for milk production
-Milk is not produced just yet due to progesterone and oestrogen blocking this specific function of PRL
-After delivery, progesterone and oestrogen lvls fall, allowing for PRL to do its thang, so milk production starts
What hormones indirectly/directly control milk production?
Directly: Prolactin and oxytocin
Indirectly: Oestrogen
What forms does PRL exist as?
-Monomer of 23kDa (60-90%)
-Big Prolactin of 40-60kDa (15-30%)
-BIG-big Prolactin (MacroProlactin) (150-170kDa)
What are some PRL analytical issues?
- Specificity
- Dynamic assay range
- Antigen excess
- Macroprolactin
What’s the Hook Effect in PRL measurement?
-High PRL conc commonly found in prolactinomas
-Very high conc (thousands) of PRL overwhelms the available binding sites in sandwuich immunoassays, giving a falsely low result
-If unexpected low/normal PRL lvls are found, serial dilution can help ID the Hook effect
There’s antigen excess causing the saturation of both the capture and labelled ab
Reduction in # of ab-ag complexes formed cuases false low results
Happens in assays in which the normal-pathological concentrations range widely
What is “BIG-big” prolactin? Does it do anything?
-It’s MacroPRL
-Some have it, some don’t
-When PRL binds to IgG (150-170kDa)
-Formed in the circulation following pituitary secretion of monomeric PRL
-MPRL remains reactive to a variable extent in immunassays
-Since it’s so big, it’s confined to the vascular system: It has no biological or pathological significance
What is “Big” Prolactin? Its size/composition? Its reactivity in immunoassays?
- Isoform of 50-60kDa of unknown composition
- May not be biologically active, just like MPRL
- 15-30% of PRL immunoreactivity in serum
- Consistent component of total serum PRL
- Very rarely the caue of hyperprolactinemia
What causes Pseudo-Hyperprolactinemia? How do you check if its pseudo or real?
- Due to MPRL
- Identify presence of MPRL in patients with elevated Tot PRL to then determine conc. of monomeric (bioactive) PRL
- Common (16%) in people with idiopathic hyperprolactinemia
How do you detect MPRL and other PRL complexes?
-Gel Filtration Chromatography is the gold standard for detect/quant of large forms of MPRL
-Anti-IgG sepharose and Protein A sepharose are used for detecting PRL-IgG complexes
-Low-solubility PRL complexes are detected through PEG precipitation
What does the “PEG” in PEG precipitation stand for?
PolyEthyleneGlycol
