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1. What are the three general chemical classes of hormones?
amines, peptides, and steroids
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2. Which catecholamine is secreted in the largest amount by the adrenal medulla, and why?
- epinephrine, because the adrenal medulla has high activity levels of the enzyme phenyl-Nmethyltransferase
- (PNMT) which converts norepinephrine into epinephrine
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3. What are the major hormones produced by the adrenal cortex? By the testes? By the ovaries?
- Adrenal cortex: cortisol, corticosterone, aldosterone, dehydroepiandrosterone (DHEA),
- androstenedione
- Testes: androgen (testosterone and dihydrotestosterone), inhibin, Müllerian-inhibiting substance
- Ovaries: estrogen (estradiol), progesterone, inhibin, relaxin
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4. Which classes of hormones are carried in the blood mainly as unbound, dissolved hormone?
- Mainly bound to plasma proteins?
- Most peptide and catecholamine hormones are carried in the blood mainly as unbound, dissolved
- hormone. Steroid and thyroid hormones are carried in the blood mainly bound to plasma proteins.
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5. Do protein-bound hormones diffuse out of capillaries?
- No. The binding proteins are too large to cross, and so only the free form of the hormone diffuses across
- the capillary membrane to encounter the target cells.
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6. Which organs are the major sites of hormone excretion and metabolic transformation?
the liver and kidneys
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7. How do the rates of metabolism and excretion differ for the various classes of hormones?
- The rates of metabolism and excretion of most peptide hormones and the catecholamines are fast—
- minutes to an hour—because they are freely dissolved in the plasma and are thus more susceptible to
- enzymatic attack. The rates for steroid and thyroid hormones are slower—hours to days. This
- difference reflects the fact that binding proteins serve a “protective” function for hormones and slow
- the rate of their removal from the blood.
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8. List some metabolic transformations that prohormones and some hormones must undergo
- before they become biologically active.
- Some hormones must be changed by metabolism to become physiologically active. An example is
- thyroxine (T4) which can be converted to a more active form, triiodothyronine (T3), in its target cells
- before binding to its receptors. Another example is renin, a hormone that acts as an enzyme to convert
- biologically inactive angiotensinogen to angiotensin I. This is the first step in the formation of
- angiotensin II. A third example is testosterone, which is converted either to estradiol or
- dihydrotestosterone in certain of its target cells. These molecules, rather than testosterone itself, then
- bind to receptors inside the target cells and elicit the cell's response.
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9. Contrast the locations of receptors for the various classes of hormones.
- The receptors for water-soluble chemical messengers like peptide and catecholamine hormones are in
- the plasma membrane of their target cells, while those for the lipid-soluble, nonpolar steroid and
- thyroid hormones are (primarily) inside the target cells, generally in the nucleus.
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10. How do hormones influence the concentrations of their own receptors and those of other
- hormones? How does this explain permissiveness in hormone action?
- Hormones can up-regulate (increase the number of) their own receptors, and down-regulate (decrease
- the number of) them. In general, high concentrations of the hormone over time lead to down-regulation
- and low concentrations over time lead to up-regulation.
- Some hormones may, by a different mechanism, increase or decrease the number of receptors for a
- different hormone. In some cases, such as epinephrine receptors in fat cells, receptor numbers are very
- low unless they are up-regulated by a low concentration of thyroid hormones. Thyroid hormone,
- therefore, causes the adipose tissue to become much more sensitive to epinephrine; this effect of thyroid
- hormones is called permissiveness.
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11. Describe the sequence of events when peptide or catecholamine hormones bind to their
- receptors.
- Binding of a peptide or catecholamine hormone to its plasma membrane receptor activates the receptor.
- When activated, the receptor triggers one or more of the signal transduction pathways described in
- Chapter 5. That is, the activated receptors directly influence: (1) enzyme activity that is part of the
- receptor; (2) activity of cytoplasmic janus kinases associated with the receptor; or (3) G proteins
- coupled in the plasma membrane to effector proteins—ion channels and enzymes that generate second
- messengers such as cAMP and Ca2+. The opening or closing of ion channels causes a change in the
- electrical potential across the membrane, and when a Ca2+ channel is involved, a change in the
- cytosolic concentration of this important ionic second messenger. The changes in enzyme activity
- rapidly produce—most commonly by phosphorylation catalyzed by protein kinase enzymes—changes
- in the conformation and hence the activity of various cellular proteins. In some cases the signal
- transduction pathways also lead to the activation or the inhibition of particular genes, causing a
- change in the rate of synthesis of the proteins coded for by these genes.
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12. Describe the sequence of events when steroid or thyroid hormones bind to their receptors.
- These hormones have intracellular receptors. Binding of such a hormone to its receptor, generally in
- the nucleus, leads to the activation or inhibition of transcription of particular genes, causing a change
- in the rate of synthesis of the proteins coded for by those genes. The ultimate result of changes in the
- concentration of these proteins is an enhancement or inhibition of particular processes carried out by
- the cell, or a change in the rate of protein secretion by the cell.
- In some cases, target cells for certain steroid hormones also have plasma membrane receptors for
- the hormone. In these cases, binding of the hormone to its plasma membrane receptor initiates
- activation of signal transduction pathways that elicit fast, nongenomic cell responses, while the
- intracellular receptor mediates a delayed response to the hormone.
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13. What are the direct inputs to endocrine glands controlling hormone secretion?
- Most hormone secretion by endocrine glands is controlled by changes in the plasma concentrations of
- mineral ions or organic nutrients, by neurotransmitters released from neurons ending on the
- endocrine cell, or by another hormone (or paracrine substance) acting on the endocrine cell.
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14. How does control of hormone secretion by plasma mineral ions and nutrients achieve
- negative feedback control of these substances?
- In the case of hormones whose secretion is affected by plasma concentrations of mineral ions or
- nutrients, a major function of the hormone is to regulate the plasma concentration of that ion or
- nutrient. For example, insulin-secreting cells in the pancreas respond to increased plasma
- concentration of glucose by increasing their secretion of insulin. One of the major functions of insulin
- is to increase the uptake of glucose into skeletal muscle and adipose tissue cells. This action causes the
- concentration of plasma glucose to be decreased. In this example, the receptors in the negative feedback
- loop are glucose receptors in the pancreatic cell’s plasma membrane; the afferent pathway and the
- integrative center are both contained within the same pancreatic cell; the efferent pathway is insulin
- circulating in the blood; and the effectors are the cells that respond to insulin by increasing their
- uptake of glucose.
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15. What roles does the autonomic nervous system play in controlling hormone secretion?
- The adrenal medulla is functionally a part of the sympathetic division of the autonomic nervous
- system, and adrenal medullary hormone secretion is stimulated by sympathetic preganglionic fibers. In
- addition, both sympathetic and parasympathetic postganglionic fibers innervate other endocrine gland
- cells, such as in the endocrine pancreas, and inhibit or stimulate hormone secretion.
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16. What groups of hormone-secreting cells receive input from neurons located in the brain
- rather than in the autonomic nervous system?
- The hormones secreted by the hypothalamus and by the anterior and posterior pituitary glands.
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17. How would you distinguish between primary and secondary hyposecretion of a hormone?
- Between hyposecretion and hyporesponsiveness?
- Primary hyposecretion of a hormone is caused by a defect in the gland that secretes the hormone.
- Secondary hyposecretion of a hormone is caused by too little stimulation of the gland by its tropic
- hormone. One way to diagnose hyposecretion is to administer the tropic hormone. In primary
- hyposecretion, the target gland for the tropic hormone is damaged leading to its failure to respond
- normally. In secondary hyposecretion, the target gland was initially normal, but has atrophied due to
- lack of tropic hormone stimulation, so it does not respond normally to stimulation. The latter condition
- can be reversed over time with normalization of tropic hormone input. Another way to distinguish
- between primary and secondary hyposecretion is to measure the level of the tropic hormone in the
- blood. If elevated, the cause is primary; if not elevated, the cause is secondary.
- If a person has primary hypothyroidism, for example, such analysis would show low levels of TH
- and high levels of TSH in plasma, because the pituitary would be functioning normally and secreting
- increased amounts of TSH due to too little negative-feedback signal from TH. If the pituitary were at
- fault, the concentrations of both TH and TSH would be low. However, this last finding would not rule
- out a problem at the hypothalamic level, in which case there would be secondary hyposecretion of TSH
- and tertiary hyposecretion of TH, ultimately due to lower than normal levels of TRH release from the
- hypothalamus. Unfortunately, the concentration of the hypophysiotropic hormones in the peripheral
- plasma is too low to measure. However, one could rule out the pituitary as the cause of the defect if the
- administration of TRH produced an increase in TSH secretion.
- Hyporesponsiveness occurs when target cells of a hormone do not respond normally to the
- hormone. To differentiate this condition from hyposecretion, one would measure the concentration of
- the hormone in plasma. If hyporesponsiveness is the problem, the hormone concentration would be
- normal or elevated, but the response of target cells to administered hormone would be diminished.
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