MCAT Biological and Biochemical Foundations of Living Systems Quiz: 3a Endocrine Glands Hormone Classes

What this quiz covers

This quiz focuses on 3a Endocrine Glands Hormone Classes, giving you a quick way to practice the rules, question types, and explanations that matter most for MCAT Biological and Biochemical Foundations of Living Systems.

How to use this quiz

Try each quiz question before looking at the correct answer. Use the explanations to review missed ideas, then come back to similar questions until the pattern feels familiar.

Question 1

1. Rapid (seconds) activation of membrane ion channels via a GPCR and second messenger cascade in distal nephron cells
2. Increased transcription of transport proteins following intracellular receptor binding, with effects blunted by blocking hormone–DNA interactions (correct answer)
3. Direct phosphorylation of cytosolic kinases by a receptor tyrosine kinase on the basolateral membrane, independent of gene transcription
4. Primary positive feedback in which rising arterial pressure further increases hormone secretion to amplify Na$^+$ retention

Explanation: This question tests understanding of endocrine gland functions and hormone classification, specifically distinguishing steroid hormones from peptides based on solubility and signaling mechanisms. Steroid hormones are lipid-soluble, diffuse into cells, and bind intracellular receptors to regulate gene transcription, producing delayed effects. In this vignette, the hormone from the adrenal cortex modulates renal sodium handling and blood pressure via transcriptional changes in transport proteins. Choice B logically follows because the delayed rise in pressure, increased channel expression, and blunting by a DNA-binding antagonist align with steroid mechanisms requiring gene regulation. Choice A fails as it describes rapid peptide hormone action via GPCRs, which contradicts the lipid solubility and gradual effects observed. To reason about hormone systems, evaluate onset time: rapid effects suggest membrane receptors typical of peptides, while delayed transcriptional changes indicate steroids. Additionally, confirm feedback type—negative feedback, as here, stabilizes variables by opposing changes.

Question 2

1. Loss of peripheral hormone production would reduce negative feedback, increasing secretion of the pituitary peptide (correct answer)
2. Loss of peripheral hormone production would increase negative feedback, decreasing secretion of the pituitary peptide
3. Peripheral hormone deficiency would be compensated by immediate upregulation of intracellular receptors without changing pituitary output
4. Peripheral hormone deficiency would primarily increase aldosterone-mediated Na$^+$ retention due to shared nuclear receptors

Explanation: This question examines endocrine axis functions and hormone classes, focusing on pituitary peptides and peripheral lipid-soluble hormones in metabolic regulation. Pituitary peptides stimulate peripheral glands, with lipid-soluble products exerting negative feedback to modulate secretion. The scenario describes a thyroid axis where elevated peripheral hormone suppresses pituitary output. Choice A follows as peripheral disruption reduces feedback, increasing pituitary peptide to compensate. Choice B fails by predicting decreased secretion, misunderstanding negative feedback loss. For reasoning, trace axis: low peripheral hormone lifts inhibition, raising upstream peptides. Check homeostasis impact: compensatory increases aim to restore levels but may fail in primary gland defects.

Question 3

1. It binds a nuclear receptor to directly increase transcription of glycogen phosphorylase, requiring hours to act
2. It binds a membrane receptor coupled to G$\alpha_s$, increasing cAMP to rapidly promote glycogenolysis (correct answer)
3. It diffuses through the membrane and activates receptor tyrosine kinases in the nucleus to increase cAMP
4. It decreases hepatic glucose output to restore glucose via negative feedback on glycogen breakdown pathways

Explanation: This question tests endocrine roles in glucose homeostasis and classification of pancreatic peptides that counter low glucose. Peptide hormones bind membrane GPCRs to rapidly activate second messengers like cAMP for metabolic shifts. Here, the hormone promotes hepatic glycogenolysis during fasting via cAMP elevation. Choice B aligns as Gs coupling, rapid cAMP rise, and inhibitor effects match peptide mechanisms. Choice A errs by describing steroid-like transcription, inconsistent with rapid onset. For reasoning, link rapid metabolic changes to GPCR signaling in peptides. Confirm counter-regulatory role: secretion rises in hypoglycemia, opposing the fall via negative feedback.

Question 4

1. Both hormones must bind DNA response elements because phosphorylation events require transcriptional priming
2. Hormone M likely requires carrier proteins in plasma because peptides are poorly soluble in water
3. Hormone N likely signals through ligand-gated ion channels because delayed effects require slow channel kinetics
4. Hormone M likely signals through membrane receptors and second messengers, whereas Hormone N likely signals through intracellular receptors to regulate transcription (correct answer)

Explanation: This question compares pancreatic peptide and adrenal steroid classifications by signaling speed and mechanisms. Peptides induce rapid phosphorylation via membrane receptors; steroids cause delayed expression via intracellular ones. The vignette contrasts quick enzyme phosphorylation and slow expression increase. Choice D is correct as mechanisms match classes. Choice B fails, wrongly claiming peptides need carriers. To reason, contrast timelines: seconds for peptides, hours for steroids. Use inhibitors: transcription blocks steroids, not peptides.

Question 5

1. Increased receptor sensitivity leading to exaggerated downstream phosphorylation and reduced appetite
2. Receptor or post-receptor resistance that blunts intracellular signaling despite high hormone levels, impairing homeostatic regulation of intake (correct answer)
3. Conversion of negative feedback to positive feedback, causing the hormone to suppress its own secretion and lower its plasma level
4. Primary endocrine gland failure, which would be expected to lower circulating hormone levels rather than elevate them

Explanation: This question tests adipose peptide functions in energy homeostasis and signaling disruptions. Peptides bind hypothalamic receptors for phosphorylation-mediated appetite control; resistance blunts responses. The vignette describes high hormone without intake reduction, with reduced phosphorylation. Choice B aligns as resistance impairs signaling despite levels. Choice A fails, suggesting hypersensitivity, opposite to blunted effects. For reasoning, correlate levels and effects: high without response indicates resistance. Examine downstream: reduced signaling confirms post-receptor defect.

Question 6

1. Serum calcium would increase because loss of the gland removes a hormone that normally increases osteoclast activity
2. Serum calcium would decrease because loss of the gland removes a hormone that normally raises calcium, and reduced thyroid calcium-lowering hormone reflects compensatory negative feedback (correct answer)
3. Serum calcium would be unaffected because calcium regulation is controlled exclusively by steroid hormones from the adrenal cortex
4. Serum calcium would decrease because the thyroid calcium-lowering hormone rises via positive feedback when calcium is low

Explanation: This question tests understanding of calcium homeostasis involving the parathyroid glands and calcitonin feedback regulation. The gland "posterior to the thyroid" refers to the parathyroid glands, which secrete PTH (parathyroid hormone) to raise serum calcium by increasing bone resorption, kidney reabsorption, and vitamin D activation. Loss of parathyroid function causes hypocalcemia and the described neuromuscular irritability from increased nerve excitability. In response to low calcium, the thyroid reduces calcitonin secretion through negative feedback—calcitonin normally lowers calcium, so its reduction represents an appropriate compensatory response to hypocalcemia. Choice A incorrectly states PTH increases osteoclast activity (it does) but wrongly predicts hypercalcemia from gland loss, while choice D misunderstands that low calcium reduces (not increases) calcitonin through negative feedback. The key principle is that calcium regulation involves opposing hormones: PTH raises calcium while calcitonin lowers it, with each responding inversely to calcium levels.

Question 7

1. Hormone X primarily binds cytosolic/nuclear receptors to alter gene transcription, whereas Hormone Y primarily binds cell-surface receptors to trigger second-messenger signaling (correct answer)
2. Hormone X is stored in vesicles for rapid exocytosis, whereas Hormone Y diffuses across membranes and requires a carrier protein in plasma
3. Hormone X acts through a membrane receptor tyrosine kinase, whereas Hormone Y directly binds DNA response elements in the nucleus
4. Hormone X and Hormone Y both require intracellular receptors because only intracellular receptors can mediate endocrine signaling

Explanation: This question tests the fundamental distinction between steroid and peptide hormone mechanisms based on their chemical properties. Hormone X, being lipid-soluble and cholesterol-derived (a steroid), can diffuse through plasma membranes and bind to cytosolic or nuclear receptors, altering gene transcription over hours—matching the described time course. Hormone Y, being water-soluble and stored in granules (a peptide/protein hormone), cannot cross membranes and must bind cell-surface receptors to trigger rapid second-messenger cascades within minutes. The vignette provides classic distinguishing features: steroid hormones require carrier proteins in blood due to their hydrophobicity, while peptide hormones are stored in vesicles for rapid release. Choice B reverses these properties, while choice C incorrectly assigns receptor tyrosine kinase signaling to the steroid. The key principle for distinguishing hormone classes is that lipid solubility determines whether a hormone can enter cells (steroids) or must signal from outside (peptides).

Question 8

1. The hormone requires a cell-surface receptor, and the antagonist fails only because it is not a high-affinity ligand
2. The hormone binds an intracellular receptor, so an extracellular antagonist that cannot enter cells will not block receptor binding and transcriptional effects (correct answer)
3. The hormone is stored in secretory vesicles and acts through rapid phosphorylation cascades, explaining the delayed transcriptional response
4. The hormone increases transcription by directly activating ribosomes in the cytosol without receptor involvement

Explanation: This question tests understanding of steroid hormone mechanism of action based on experimental antagonist results. The hormone's lipid solubility and cholesterol derivation identify it as a steroid (likely testosterone or estrogen from gonads), which must cross the plasma membrane to bind intracellular receptors and alter gene transcription—explaining the 6-hour delay for transcriptional effects. The critical experimental finding is that an extracellular antagonist fails to block the hormone's action, proving the receptor must be intracellular since the membrane-impermeant antagonist cannot reach it. Choice A incorrectly suggests the hormone uses surface receptors, contradicting both its lipid solubility and the antagonist results, while choice C wrongly attributes steroid properties (vesicular storage) to this lipid-soluble hormone. The diagnostic principle for identifying intracellular receptors is that only membrane-permeant antagonists can block their activation, as extracellular compounds cannot access the cytoplasmic or nuclear binding sites.

Question 9

1. Pituitary peptide decreases because reduced thyroid hormone removes negative feedback and suppresses pituitary secretion
2. Pituitary peptide increases because reduced thyroid hormone weakens negative feedback, increasing pituitary drive to the thyroid (correct answer)
3. Pituitary peptide is unchanged because iodinated thyroid hormones are peptides and do not regulate pituitary secretion
4. Pituitary peptide decreases because the inhibitor directly activates pituitary membrane receptors through second-messenger signaling

Explanation: This question tests understanding of thyroid hormone synthesis and pituitary-thyroid feedback regulation. Thyroid hormones (T3/T4) are amine-derived from tyrosine but behave like steroids, requiring proteolysis of thyroglobulin to release active hormones from follicular cells. The first part establishes normal negative feedback: when thyroid hormone secretion increases, it suppresses TSH (thyroid-stimulating hormone) from the anterior pituitary. When the proteolysis inhibitor prevents thyroglobulin breakdown, less thyroid hormone is released despite normal iodination, creating a functional hypothyroid state. This reduction in circulating thyroid hormone weakens negative feedback on the pituitary, causing TSH levels to increase as the pituitary attempts to stimulate more thyroid hormone production. Choice A incorrectly predicts TSH decrease when reduced negative feedback must increase pituitary secretion, while choice C wrongly claims thyroid hormones are peptides. The principle for understanding pituitary-thyroid feedback is that thyroid hormones suppress their own production by inhibiting TSH, so any decrease in thyroid hormone levels will increase TSH through disinhibition.

Question 10

1. Decreased synthesis of peptide hormones in rough ER with reduced vesicular storage, leading to decreased upstream signaling via negative feedback
2. Decreased synthesis of steroid hormones from cholesterol, leading to reduced negative feedback and increased upstream trophic signaling with gland hypertrophy (correct answer)
3. Increased synthesis of steroid hormones due to substrate trapping, leading to suppression of upstream signals and adrenal atrophy
4. Selective impairment of iodinated hormone synthesis in the thyroid, leading to increased renal water loss and adrenal hypertrophy

Explanation: This question tests steroid hormone biosynthesis in the adrenal cortex and compensatory feedback in the hypothalamic-pituitary axis. Steroid hormones are synthesized from cholesterol via enzymatic cleavage, with deficiencies triggering reduced negative feedback and upstream trophic stimulation leading to gland hypertrophy. The vignette shows inhibited cleavage lowering adrenal steroids, followed by increased hypothalamic/pituitary signals and cortical hypertrophy. Choice B aligns, as low steroids reduce feedback, elevating ACTH to induce hypertrophy. Choice A fails by describing peptide synthesis impairment, misconstruing the drug's target as ER-based rather than cholesterol metabolism. For hormone systems, link biochemical class to synthesis pathways and predict feedback responses. Assess long-term effects by noting adaptations like hypertrophy from sustained trophic drive.

Question 11

1. Rapid activation of a membrane GPCR leading to increased cAMP and immediate glycogen breakdown within seconds, independent of transcription
2. Diffusion into target cells followed by receptor binding and altered gene transcription, with negative feedback reducing upstream pituitary signaling (correct answer)
3. Binding to a cell-surface receptor tyrosine kinase that triggers vesicular insertion of glucose transporters into skeletal muscle membranes
4. Secretion into bile for enterohepatic recycling, producing positive feedback that elevates the upstream pituitary signal

Explanation: This question tests the understanding of steroid hormone mechanisms in the endocrine system, focusing on their classification as lipophilic signals from glands like the adrenal cortex and their role in stress responses. Steroid hormones, derived from cholesterol, are lipophilic and can diffuse across cell membranes to bind intracellular receptors, ultimately altering gene transcription. In this vignette, the hormone from the zona fasciculata is likely a glucocorticoid like cortisol, which increases during stress and induces gluconeogenic enzyme expression over minutes to hours. The observations of decreased cytosolic receptors, increased nuclear receptor-DNA complexes, and reduced upstream pituitary signaling (ACTH) logically follow from the steroid's mechanism of nuclear translocation and negative feedback on the hypothalamic-pituitary-adrenal axis, as described in choice B. A distractor like choice A fails by describing a peptide hormone mechanism involving rapid GPCR signaling and second messengers, which would not involve transcriptional changes or the observed receptor dynamics, misconstruing the hormone class's solubility and action timeline. To reason about hormone systems, always classify hormones by solubility to predict receptor location and onset of effects. Additionally, evaluate feedback loops by checking if downstream signals inhibit upstream regulators to maintain homeostasis.

Question 12

1. The peripheral lipid-soluble hormone increases tropic hormone clearance by renal filtration because carrier proteins prevent reabsorption
2. The hypothalamic releasing peptide exerts direct positive feedback on the pituitary, so tropic hormone levels should rise indefinitely during infusion
3. The pituitary tropic hormone is lipid-soluble and therefore cannot be secreted efficiently into blood, causing low measured levels
4. The peripheral lipid-soluble hormone exerts negative feedback at the pituitary and/or hypothalamus, limiting tropic hormone secretion despite ongoing hypothalamic stimulation (correct answer)

Explanation: This question tests understanding of hierarchical negative feedback in the hypothalamic-pituitary-peripheral axis. The continuous infusion of hypothalamic releasing hormone (like CRH or GnRH) initially stimulates the pituitary to secrete its tropic hormone (ACTH or LH/FSH), which then stimulates the peripheral gland to produce a steroid hormone. However, as peripheral steroid levels rise over 48 hours, they exert negative feedback at both the pituitary and hypothalamus, suppressing tropic hormone secretion despite ongoing hypothalamic stimulation. This explains why pituitary hormone levels are "lower than expected"—the elevated peripheral steroid overrides the stimulatory signal through feedback inhibition. Choice B incorrectly invokes positive feedback, which would cause uncontrolled hormone escalation, while choice C wrongly claims pituitary hormones are lipid-soluble when they are peptides. The key principle in multi-level endocrine axes is that peripheral hormones regulate their own production through negative feedback at multiple upstream sites.

Question 13

1. Blood pressure would increase because blocking the upstream renal enzyme elevates the steroid and enhances sodium retention
2. Plasma potassium would decrease because reduced steroid signaling lowers potassium secretion in the distal nephron
3. Blood pressure would fall and plasma potassium would rise because reduced steroid signaling decreases sodium reabsorption and decreases potassium excretion (correct answer)
4. Urinary sodium would increase because the steroid is a peptide that acts through aquaporin insertion rather than ion transport regulation

Explanation: This question tests understanding of mineralocorticoid action and the renin-angiotensin-aldosterone system (RAAS). The steroid hormone is aldosterone from the adrenal cortex, which promotes sodium retention and potassium excretion in kidney collecting ducts, thereby increasing blood volume and pressure. The drug blocks the upstream enzyme (likely ACE or renin), preventing the cascade that stimulates aldosterone production. Without adequate aldosterone signaling, the kidney cannot retain sodium effectively (lowering blood pressure) and cannot excrete potassium normally (raising plasma potassium)—both effects described in choice C. Choice A predicts opposite effects by misunderstanding that blocking the upstream enzyme reduces (not increases) aldosterone, while choice D incorrectly identifies aldosterone as a peptide when it's clearly described as a steroid. The key principle in RAAS disruption is that reducing aldosterone activity causes reciprocal changes: sodium loss with potassium retention, manifesting as hypotension with hyperkalemia.

Question 14

1. The hormone diffuses into osteoclasts and binds nuclear receptors to downregulate resorption genes directly
2. The hormone binds cell-surface receptors and triggers second messengers to rapidly alter osteoclast activity (correct answer)
3. The hormone is transported bound to carrier proteins and accumulates in adipose tissue, delaying effects
4. The hormone increases serum calcium through a positive feedback loop to further stimulate its own secretion

Explanation: This question tests thyroid peptide functions in calcium homeostasis and classification via rapid signaling. Peptides bind membrane receptors, using second messengers for quick cellular modulation like inhibiting bone resorption. Here, the hormone lowers calcium by reducing osteoclast activity, with G-protein involvement. Choice B aligns as rapid effects and G-protein blockade fit peptide mechanisms. Choice A is incorrect, applying steroid nuclear binding to a rapid process. For reasoning, associate immediate ion changes with membrane signaling. Confirm feedback: secretion rises with high calcium, negatively feeding back to lower it.

Question 15

1. It would increase gene transcription because preventing nuclear entry concentrates the receptor near DNA
2. It would reduce downstream gene expression and weaken negative feedback, potentially increasing upstream pituitary peptide secretion (correct answer)
3. It would convert negative feedback into positive feedback, decreasing pituitary secretion when hormone levels fall
4. It would have minimal effect because lipid-soluble hormones act primarily through membrane GPCRs

Explanation: This question examines gonadal steroid functions and receptor dynamics in reproductive homeostasis. Steroids require nuclear translocation for transcriptional regulation and negative feedback. The vignette describes feedback suppression and transcription blocked by translocation inhibition. Choice B is consistent as impaired nuclear entry reduces expression and feedback, increasing pituitary output. Choice A is wrong, illogically claiming concentrated receptors enhance transcription. To reason, disrupt steps: blocking nuclear access halts steroid effects. Predict axis: weakened feedback elevates upstream secretion.

Question 16

1. It would increase water reabsorption by upregulating intracellular steroid receptors in collecting duct cells
2. It would decrease the ability to concentrate urine by preventing rapid, receptor-mediated insertion of water channels into the apical membrane (correct answer)
3. It would cause sustained positive feedback, with rising osmolality suppressing hormone release and further lowering osmolality
4. It would primarily alter erythropoiesis by reducing transcription of globin genes in bone marrow

Explanation: This question assesses endocrine gland roles and hormone classification, emphasizing peptide hormones from the posterior pituitary that enable rapid membrane changes. Peptide hormones bind GPCRs to induce second messengers, facilitating quick responses like channel insertion for water reabsorption. The scenario involves osmoregulation where the hormone counters dehydration by concentrating urine via aquaporin trafficking. Choice B follows logically as the antagonist's prevention of urine concentration and channel insertion aligns with disrupted rapid peptide signaling. Choice A fails by attributing steroid-like intracellular receptor upregulation to a rapid, peptide-mediated process, confusing classes. To reason effectively, check if blockade affects immediate membrane events (peptides) or delayed transcription (steroids). Confirm negative feedback: rising osmolality stimulates release to oppose the change, maintaining homeostasis.

Question 17

1. The hormone enters the nucleus and directly binds DNA to initiate transcription without a receptor
2. The hormone binds a membrane receptor whose activation triggers intracellular kinase signaling, leading to downstream gene expression changes (correct answer)
3. The hormone must be carried by plasma binding proteins to reach the liver because it is lipid-soluble
4. The hormone's main effect is immediate transcriptional repression through intracellular receptors, explaining the 5-minute response

Explanation: This question assesses anterior pituitary peptide classification, focusing on growth promotion via membrane receptors. Peptides bind cell-surface receptors, activating kinases for signaling cascades leading to gene expression. The scenario involves rapid phosphorylation and delayed mediator production in liver. Choice B follows as kinase activation and receptor dimerization fit peptide mechanisms. Choice A errs by claiming direct DNA binding without receptors, impossible for peptides. For reasoning, note early signaling precedes transcriptional effects in peptides. Blockade at receptor confirms membrane initiation.

Question 18

1. Upregulation of intracellular transcription after the hormone diffuses through the plasma membrane and binds a nuclear receptor
2. Decreased firing of hypothalamic osmoreceptors leading to reduced endogenous pituitary hormone release via negative feedback (correct answer)
3. Increased endogenous pituitary hormone secretion because the analog initiates a positive-feedback loop to amplify water retention
4. Primary increase in erythropoiesis due to direct stimulation of bone marrow receptors on hematopoietic stem cells

Explanation: This question tests understanding of peptide hormone action and negative feedback regulation in the posterior pituitary-kidney axis controlling water balance. The synthetic analog mimics ADH (vasopressin), a peptide hormone that cannot cross cell membranes and must bind to surface receptors on kidney collecting duct cells to increase water reabsorption. The vignette shows classic ADH effects: decreased urine flow, increased urine concentration, and decreased plasma osmolarity as water is retained. When plasma osmolarity falls from 296 to 288 mOsm/kg, hypothalamic osmoreceptors detect this hypoosmotic state and reduce their firing rate, which decreases endogenous ADH release from the posterior pituitary—a negative feedback response. Choice A incorrectly describes steroid hormone action (nuclear receptors), while choice C wrongly suggests positive feedback when water homeostasis clearly involves negative feedback. To reason through hormone feedback, identify whether the hormone's effect opposes (negative) or amplifies (positive) the initial stimulus—here, water retention opposes the initial high osmolarity.

Question 19

1. Endogenous adrenal steroid levels would rise because receptor binding by Compound Z reduces negative feedback to the hypothalamus and pituitary
2. Endogenous adrenal steroid levels would fall because receptor activation by Compound Z mimics the hormone and strengthens negative feedback on upstream hormone release (correct answer)
3. Endogenous adrenal steroid levels would be unchanged because steroid hormones do not participate in feedback loops
4. Endogenous adrenal steroid levels would fall because Compound Z prevents secretion by blocking vesicular exocytosis in adrenal cortical cells

Explanation: This question tests understanding of steroid hormone feedback regulation in the hypothalamic-pituitary-adrenal (HPA) axis. Compound Z acts as a steroid hormone mimic, binding the same intracellular glucocorticoid receptor as the endogenous adrenal cortical hormone (cortisol). When Compound Z activates these receptors, it produces glucocorticoid-like effects (increased glucose, immunosuppression) while simultaneously triggering negative feedback to the hypothalamus and anterior pituitary. This negative feedback reduces CRH and ACTH secretion, which decreases stimulation of the adrenal cortex and lowers endogenous steroid production—explaining the observed reduction in plasma levels. Choice A incorrectly predicts increased steroid levels by misunderstanding that receptor activation (not just binding) drives feedback, while choice D wrongly attributes the effect to vesicular blockade when steroids are synthesized on demand, not stored. The principle for endocrine disruption is that exogenous compounds mimicking hormones will suppress endogenous production through the same feedback loops that maintain homeostasis.

Question 20

1. It increases upstream pituitary secretion by positive feedback to maintain stable hormone levels
2. It binds a membrane receptor and directly phosphorylates ion channels, causing immediate changes in heart rate
3. It requires vesicular fusion at target cells to enter the cytosol, explaining delayed onset
4. It binds a cytosolic/nuclear receptor that regulates transcription and participates in negative feedback on upstream pituitary output (correct answer)

Explanation: This question evaluates thyroid hormone classification as lipid-soluble with transcriptional effects in metabolism. Such hormones bind cytosolic/nuclear receptors to regulate genes, influencing energy use with feedback on pituitary. The vignette shows delayed protein expression and oxygen changes in heart cells. Choice D is correct as DNA binding dependence and negative feedback match steroids. Choice B fails, describing rapid phosphorylation unfit for delayed onset. To reason, link slow metabolic shifts to transcription. Trace feedback: elevated hormone suppresses upstream peptides.