Chapter 3 — Exercises

Items marked † have worked solutions in Appendix M.

A. Recall

3.1 Name the three tiers of a classical endocrine axis and give an example hormone at each.

3.2 † What is the hypothalamic-pituitary portal circulation, and why does it exist?

3.3 Name the four major axes and the final hormone each produces.

3.4 Define negative feedback and set point.

3.5 † Which axis has an explicit inhibitory hypothalamic hormone as well as a stimulatory one? Name both.

3.6 Define pulsatility. Give the two hormones from this chapter whose release is most strikingly pulsatile.

3.7 What is counter-regulation? Give the chapter's principal example.

3.8 Name four organs that are now recognized as endocrine organs but are not on the classical list.

B. Feedback and suppression

3.9 † Explain, step by step, why supplying a hormone from outside reduces your own production. Include why the system cannot distinguish the two sources.

3.10 Predict what happens to endogenous production for each: (a) exogenous testosterone; (b) exogenous growth hormone; (c) long-term high-dose corticosteroid; (d) a GLP-1 receptor agonist. Explain any that differ from the others and why.

3.11 † Why is abrupt withdrawal of long-term corticosteroid therapy dangerous, and why does tapering help? Answer in terms of §3.4.

3.12 A secretagogue successfully raises growth hormone. Using §3.4, explain what the axis does in response — and why "the feedback loop is preserved" does not mean "feedback does not apply."

3.13 Construct the general rule you would use to predict whether a novel peptide drug will suppress its endogenous counterpart. State it in one sentence, then test it against GLP-1.

C. Pulsatility

3.14 † Explain why a single random blood measurement of growth hormone is nearly uninterpretable, and what is measured instead.

3.15 GnRH given in pulses stimulates the reproductive axis; given continuously it suppresses it. Explain both outcomes using Chapter 2's termination mechanisms.

3.16 Leuprolide is a GnRH agonist used to suppress sex hormone production in cancer treatment. Explain to someone who has just learned what "agonist" means why this is not a contradiction.

3.17 † A compound is described as producing a "sustained elevation" of a hormone that is naturally pulsatile. State three distinct reasons this might produce less benefit than expected, and one reason it might produce a benefit the natural pattern would not.

D. "Explain this to a friend"

3.18 † Explain to someone with no biology background why taking a hormone can make your body stop making its own. Use an everyday analogy. Under five sentences.

3.19 Your friend is confused that GLP-1 drugs do not shut down their own GLP-1, when they have heard testosterone does shut down their own testosterone. Explain the difference without using the words axis, feedback, or set point.

3.20 Explain the incretin effect — the actual experiment — to someone who has heard of Ozempic and nothing else. Three sentences.

E. Applied reasoning

3.21 For each drug, state the tier it acts on, whether it is agonist or antagonist, whether its delivery matches the natural pattern, and what feedback does in response: recombinant growth hormone; a GHRH analog; leuprolide; degarelix; semaglutide; insulin in type 1 diabetes.

3.22 † Somatostatin inhibits growth hormone, insulin, glucagon, and several gut hormones. A somatostatin analog is an approved drug (Ch 27). Predict, from §3.3 and §3.6 alone, what side effects such a drug might plausibly have — and then state how you would check whether your predictions are right.

3.23 The gut releases GLP-1 in response to nutrients arriving, not in response to circulating GLP-1 levels. Explain why this architectural detail is the reason GLP-1 drugs behave differently from pituitary hormone replacement.

3.24 † Natriuretic peptides earn a strong rating as a biomarker and a much weaker one as an infused therapy, while a drug that blocks their breakdown succeeded. Explain how one system can produce three different verdicts, and state what this implies about rating molecules versus rating claims.

F. Identify the red flags

3.25 A clinic's website states: "Our peptide protocols restore your body's natural hormonal balance without the shutdown associated with hormone replacement." Identify at least four distinct unsupported claims in that sentence.

3.26 † A product claims to "optimize the HPA axis for better stress resilience." Rewrite it as specifically as evidence would have to be, then identify which of §2.9's seven steps each specification corresponds to.

G. Judgment

3.27 The incretin story is a forty-year basic-science investment that produced a multi-billion-dollar drug class. Nobody working on gut hormone physiology in 1975 knew where it led. What does this suggest about how to evaluate research whose applications are not yet visible? Argue a position, and identify the strongest counterargument.

3.28 † §3.5 shows that a mechanistically sound agonist can produce the opposite of the intended effect purely because of delivery pattern. Does this strengthen or weaken the argument in §2.9 that mechanism is insufficient? Be precise about which part of the mechanism was and was not understood.

H. Evidence Dossier extension

3.29 † Complete Field 2 (Origin) for every peptide in your dossier, including the feedback and natural pattern lines.

3.30 For each dossier peptide, answer: is there a system upstream that measures this and turns itself down? Where the question does not apply — a wholly synthetic compound with no endogenous counterpart — record that it does not apply and say why.

3.31 Identify any peptide in your dossier where the natural pattern is pulsatile or stimulus-triggered and the drug delivery is continuous. Write one paragraph on what question that mismatch raises. You will need it in Part III.