Endocrine system

What the exam asks

The two items that appear most are a feedback axis with a step blocked, and a mechanism contrast between a steroid and a peptide. For the first, expect a table of two or three hormone levels and a question about where the lesion is: work down the axis asking what each level would be if the fault were at that point, and read the end hormone against the trophic hormone rather than either alone. The trap is intuitive and costly: candidates see a raised trophic hormone and conclude the axis is overactive, when a raised trophic hormone is the signature of a gland that is failing to answer it. For the second, the trap is sorting hormones by what they are made of instead of whether they dissolve in lipid. If a stem tells you a hormone acts within minutes on an existing enzyme, it has told you the receptor is on the surface, whatever the molecule is called.

The endocrine system is responsible for slow, distributed control: growth, metabolic rate, fuel handling, salt and water balance, the stress response and reproduction. A gland releases a hormone into the blood, which carries it everywhere, and only cells with a receptor for it respond. That last clause does most of the explaining in this topic, because it is why a signal broadcast to the whole body has effects in three tissues and not the rest.

Most of the system is arranged as an axis with negative feedback: the hypothalamus signals the anterior pituitary, the pituitary signals a gland, the gland releases the hormone that does the work, and that hormone inhibits the two steps above it. A loop like this is self-correcting, and it means the level of a hormone is never interpretable alone. What identifies the fault is the pair: the end hormone and the trophic hormone above it, read together.

The other half of the topic is mechanism, and it comes down to solubility. A lipid-soluble hormone crosses the membrane and acts on a receptor inside the cell, ending in altered gene transcription: slow to start, slow to stop. A water-soluble hormone cannot cross, so it binds a surface receptor and works through a second messenger cascade on enzymes that already exist: fast, amplified, brief. Nearly every mechanism question the exam sets is one of those two paragraphs applied to a hormone named in the stem.

What to hold

• A hormone reaches every cell but acts only on cells carrying its receptor, so the target tissue is defined by the receptor and not by the delivery.
• The same hormone can produce opposite effects in different tissues, because the receptor subtype and the machinery it is wired to differ between them.
• In a negative feedback axis the hypothalamic and pituitary hormones drive the gland, and the gland's product inhibits both of them.
• Block hormone production at the gland and the end hormone falls, which lifts the inhibition it was exerting, so the trophic hormone above it rises.
• The end hormone low with the trophic hormone high localises the fault to the gland; both low localises it above the gland, at the pituitary or hypothalamus.
• Giving a hormone from outside is read by the axis as the gland's own output, so it suppresses the trophic hormone and the gland idles and shrinks.
• Steroid hormones are made from cholesterol, are lipid-soluble, cross the membrane, and bind intracellular receptors that act on DNA as transcription factors.
• A steroid's effect takes hours because it requires transcription and translation, and it outlives the hormone because the proteins made have their own lifetimes.
• Peptide hormones are water-soluble, cannot cross the membrane, and bind surface receptors that act through second messengers on enzymes already present, so the response takes seconds to minutes.
• The second messenger cascade amplifies: one hormone molecule at a receptor yields many second messenger molecules and far more product, which is why hormones work at vanishingly low concentrations.
• Solubility predicts mechanism; the chemical family does not. Thyroid hormone and adrenaline are both made from tyrosine and behave in opposite ways because one is lipid-soluble and the other is not.
• Lipid-soluble hormones travel bound to plasma carrier proteins, which keeps them in solution and gives them a long half-life, while peptide hormones dissolve freely and are cleared in minutes.
• Sustained high hormone levels tend to reduce receptor numbers on the target, so the response falls even though the signal has not.