Kd vs. Ki graphs
TSH stimulation tests...
radioactive iodine uptake graphs...
What's the take home message here?
BIG IDEA: ligand concentration for maximal physiological response does not necessarily correlate with Kd! In other words, there is a certain threshold number of receptors that need to be bound, in order to induce a response. This is related to the idea of "potency" (that we didn't really talk about explicitly) which refers to how much of the drug is necessary to create a response.
What does this graph mean?
Inhibition constant (Ki) stuff...
What does this graph indicate?
Dissociation constant (Kd) stuff...
Melatonin synthesis (via N-acetyl transferase, or "SNA") peaks at night.
Explain primary failure here
Primary failure - high baseline serum TSH because the thyroid is not producing T3/4, so no negative feedback to both (1) the hypothalamus to stop secreting TRH thus promoting TSH and (2) to anterior pituitary to stop secreting TSH
Explain secondary failure here
Secondary failure is at the level of the anterior pituitary, whose job is to make TSH. Thus, the baseline TSH levels will be very low - almost null. Also, the anterior pituitary will not be responsive to TRH from the hypothalamus. That's why its a LOW and FLAT line all throughout!
What are some observations here?
After ~50 years old, BOTH men and women show an INCREASE in
Who has the most BNP?
SKINNY OLD WOMEN WITH HEART FAILURE.
Note: Normal levels of BNP rules out CHF. If abnormal, more tests needed.
Know this cold
Note which hypothalamic releasing hormones are cAMP, and which are DAG/PKC/IP3
Trick: cAMPing is stressful (CRH) for grown-ups (GHRH). Just remember GHIH goes with GHRH since antagonizing same pathway.
What hypothalamic nucleus are we seeing here?
These are POA - we're looking at GnRH cell bodies. These are released in a pulsatile manner - OBLIGATORY!
Kallman's syndrome. Migration of GnRH neurons from olfactory placode to the forebrain is inhibited by the closure of the cribiform plate. Note - patients may also have cleft lip. This is X-linked.
Oh dear. Which pathway promotes FSH/LH synthesis? Release?
BONUS: are we looking at a basophiles, or an acidophile?
IP3/Ca+ promotes RELEASE which makes sense....think about Ca2+ required for vesicles to dock and release...
DAG/PKC promotes SYNTHESIS
BONUS: we're looking at a BASOPHILE since we're talking about FSH/LH. Remember that "FLAT" from FLATPiG is basophiles (10%) while PiG is acidophiles (40%)
LH release is favored by high-frequency GnRH pulses.
FSH release is favored by low-frequency GnRH pulses.
See the YELLOW arrow. Let's focus on AVP for now. What kind of neurons are found here that secrete AVP? What hypothalamic nuclei do they originate from?
The AVP secreting cells come from magnocellular neuron, whose cell bodies originate in hypothalamic PVN and SON. They regulate WATER BALANCE (not stress).
Green arrow. The AVP-secreting neurons here come from the __________ divison of _________ in the hypothalamus.
Which arrow secretes FLAT PiG?
Which arrow secretes a hormone that induces LACTATION?
Which arrow secretes a hormone that promotes milk EJECTION?
Which arrow contains tissue derived from neuro-ectoderm?
Which arrow contains glandular tissue, and secretes FLAT PiG?
Yellow. Anterior pituitary.
What are these red things? Do What kind of neurons do they belong to? What will they secrete?
Herring bodies (axon terminals) of magnocellular neurons. If their cell bodies live in the PVN, they will secrete AVP + NP2. If their cell bodies live in the SON, they will secrete OXY and NP1.
What are the purple dots
pituicytes - glial cells of post. pituitary
To be continued starting at
handout page 35