Fig. 18-1, p. 612

Ch. 18 – The Endocrine System • = all cells, tissues, and organs that produce hormones (= chemical messengers) that have effects on target cells elsewhere in the body • Is needed to control coordinated, widespread activities and gradual, sustained, long-term processes – E.g. metabolism, growth, development, reproduction, etc.

Intercellular communication

(local hormones)

(the nervous system)

= long distance control (generally) Table 18-1, p. 610

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Nervous vs. endocrine control Characteristic

Nervous

Control messenger

Neurotransmitter released at synapse

Hormone released into bloodstream

Cells affected

Muscle cells, glands, adipocytes, other neurons

All body cells that have receptors for hormone (= target cells)

Muscle contraction, glandular secretion, neurotransmitter release

Change in metabolic activities of target cells

Usually milliseconds

Seconds, minutes, hours, or days

Generally briefer

Generally longer

Typically negative feedback

Typically negative feedback

Results of stimulus

Time to effect Duration of effect Control mechanism

Endocrine

An overview of the endocrine system, part 1

Fig. 18-1, part 1, p. 612

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An overview of the endocrine system, part 2

Fig. 18-1, part 2, p. 612

Classes of hormones • There are 3 main groups based on chemical structure: – 1. Amino acid derivatives (biogenic amines) – 2. Peptide hormones – 3. Lipid derivatives

Fig. 18-2, p. 613

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Amino acid derivatives

Fig. 18-2, part 1, p.613

Peptide hormones

Fig. 18-2, part 2, p. 613

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Lipid derivatives Note: eicosanoids are mostly paracrine (local) in their effects and are discussed in other chapters

Fig. 18-2, part 3, p. 613

Hormone transport and breakdown • Transport of hormones: – A. Water-soluble hormones – freely circulate in the bloodstream; they are not bound to carrier molecules • E.g. catecholamines (E, NE, and dopamine), and peptides/proteins • In general, they bind to receptors located on the outer surface of target cells (i.e., plasma membrane receptors) • They remain active (able to bind to a receptor on a target cell) ~ 2 minutes to 1 hour

– B. Lipid-soluble hormones – most do not freely circulate; instead, about 99% of them are bound to water-soluble carrier molecules when in the bloodstream • E.g. steroids and thyroid hormones • In general, they bind to receptors located within target cells (i.e., intracellular receptors) • They form a long-lasting (several weeks’ supply) hormone reserve

• Freely circulating hormones are inactivated when they: – 1. Bind to receptors on or within target cells – 2. Are broken down by the liver or kidneys – 3. Are broken down by enzymes in the blood plasma or interstitial fluids

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Hormone receptors and target cells • Receptor = usually a protein, located: – At the surface of the plasma (cell) membrane (plasma membrane receptors), OR… – Within the cytoplasm or nucleus, or on mitochondria (intracellular receptors)

Fig. 18-3, p. 615

• Target cell = a cell with specific receptors for a specific hormone – If a cell does NOT have a receptor for a particular hormone, then that hormone has NO effect on that cell Fig. 18-4a, p. 617

Hormone effects • Hormones affect the proteins (often enzymes) in target cells, specifically by: – 1. Activating genes to cause the synthesis of new proteins • E.g. making a new enzyme or structural protein

– 2. Modifying the transcription or translation rate of existing proteins • E.g. making more or making less of an existing enzyme or different protein

– 3. Modifying the activity or function of existing proteins • E.g. changing the shape of an existing enzyme or membrane channel to turn it “on” or “off”

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Mechanisms of hormone action • Depend upon water- vs. lipid-solubility; in general… – Water-soluble hormones bind to plasma (cell) membrane receptors – Lipid-soluble hormones act on intracellular receptors

• Plasma membrane receptors require both first and second messengers: – 1. First messenger = the hormone • It binds to a plasma membrane receptor (which is usually associated with a G protein)

– 2. Second messengers = intracellular molecules that are formed due to a hormone-receptor interaction; they function to carry out the effect of the hormone within the target cell

Some other terms that are relevant to mechanisms of hormone action • Amplification – the binding of a hormone to a receptor causes many second messengers of the same type to be activated, released, or synthesized • Receptor cascade – the binding of a hormone to a receptor causes different second messengers to be activated, released, or synthesized (often as part of a linked sequence) • Down-regulation – if hormone levels are ↑ in the blood, the number of receptors ↓, causing ↓ sensitivity to the hormone • Up-regulation – if hormone levels are ↓ in the blood, the number of receptors ↑, causing ↑ sensitivity to the hormone

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↑

↓

G protein membrane receptors that affect cAMP levels Fig. 18-3, p. 615

↑

↑

G protein membrane receptors that ↑ intracellular Ca2+ levels Fig. 18-3, p. 615

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Fig. 18-4a, p. 617

Intracellular receptors for steroid hormones • Steroid hormones are lipid-soluble, so they diffuse through the cell membrane • They bind to receptors in the cytoplasm or nucleus • The hormone-receptor complex then alters gene expression • E.g. testosterone

Fig. 18-4b, p. 617

Intracellular receptors for thyroid hormones • Thyroid hormones are also considered to be lipidsoluble (but they must be selectively transported across the cell membrane) • They may bind to receptors on mitochondria, which… – ↑ ATP production

• Or they may bind to receptors in the nucleus – The hormone-receptor complex then alters gene expression

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Endocrine reflexes • There are 3 types of stimuli that can trigger an endocrine reflex, causing the release of a hormone: – 1. Humoral stimuli = a change in the composition of the blood or ECF • E.g. ↓ [Ca2+] in the blood/ECF causes the parathyroid glands to release PTH

– 2. Hormonal stimuli = the arrival or removal of a specific hormone • E.g. ACTH causes the adrenal cortex to release cortisol

– 3. Neural stimuli = action potentials arrive at a neuroglandular junction, causing the release of NT • The NT itself may enter the bloodstream and act as a hormone (e.g. the adrenal medullae release E and NE) • The NT may stimulate glandular tissue to release a different hormone (e.g. action potentials from the hypothalamus cause the posterior pituitary to release ADH and/or OXT)

• Usually, endocrine reflexes are examples of negative feedback mechanisms

Hypothalamic control of endocrine function

Fig. 18-5, p. 618

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The pituitary gland (hypophysis) • Is connected to the hypothalamus by the infundibulum • Releases 9 (!) different peptide hormones • Has 2 major parts: – 1. Anterior pituitary (anterior lobe or adenohypophysis) – 2. Posterior pituitary (posterior lobe or neurohypophysis)

Fig. 18-6, p. 619

The hypophyseal portal system • •

Portal vessels (in general) function to link two separate capillary networks The hypophyseal portal system carries regulatory hormones (releasing and inhibiting hormones) from the hypothalamus to the anterior pituitary

Fig. 18-7, p. 620

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Hypothalamic control of the anterior pituitary • • •

Releasing hormones (RHs) = regulatory hormones that stimulate the synthesis and secretion of one or more anterior pituitary hormones Inhibiting hormones (IHs) = regulatory hormones (not shown here) that inhibit the synthesis and secretion of one or more anterior pituitary hormones The pattern shown to the right is the “typical” regulatory pattern of feedback control – note that only RHs are utilized; see some specific examples in the table below

Fig. 18-8, p. 621

Hypothalamic regulatory pattern variations* *Note that both RHs and IHs are utilized here

Fig. 18-8b p. 621

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The major anterior pituitary hormones • Note: most of these are tropic hormones – which means they regulate the activity of other glands

Table 18-2, p. 625

Additional notes about GH • It has both indirect and direct effects: – Indirect effects – GH targets the liver, which then releases somatomedins, which are also known as insulin-like growth factors (IGFs) • Somatomedins stimulate skeletal muscle fibers, chondrocytes (especially those in growing bones), and other target cells to increase amino acid uptake and protein synthesis, causing cell/tissue growth and/or repair • The indirect effects of GH usually occur after a meal, when there is ↑ [glucose] and ↑ [amino acids] in the blood

– The direct effects of GH usually occur when blood [glucose] and [amino acids] are normal • 1. On epithelium and connective tissue: ↑ cell division (for tissue growth and/or repair) • 2. On adipose tissue: breakdown of stored triglycerides and release of fatty acids into the blood • 3. On the liver: breakdown of stored glycogen and release of glucose into the blood

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Posterior pituitary hormones

Table 18-2, p. 625

• Additional notes: – Both of these hormones are made by the hypothalamus, transported to the posterior pituitary via axoplasmic transport, and stored in and released by the posterior pituitary – In high concentrations, ADH also causes peripheral vasoconstriction – ADH stimuli for secretion: ↑ blood [osmotic/solute], ↓ blood volume, ↓ blood pressure – OXT stimuli for secretion (females): ↑ estrogen levels, distortion of cervix, infant suckling, sexual activity – OXT stimulus for secretion (males): sexual activity

A summary of the pituitary hormones

(see also Table 18-2 and your hormone chart) Fig. 18-9, p. 624

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Fig. 18-10, p. 627

The thyroid gland •

•

Follicle cells = the simple cuboidal epithelial cells that line the follicle, make thyroid hormones (T3 and T4), and store them with proteins (as part of a viscous fluid called colloid) in the follicle cavity C (clear) cells (a.k.a. parafollicular cells) – make calcitonin (CT)

Thyroid hormones

• • •

•

•

Iodine is a critical ingredient that is obtained from the blood in ionic form Thyroid hormones are derived from the amino acid tyrosine Thyroglobulin is the protein that helps store T3 (triiodothyronine) and T4 (thyroxine or tetraiodothyronine) Thyroid hormones are carried in the blood bound to transport proteins (e.g. TBG); there is a reserve supply of more than one week Most (85-90%) of what is made by the thyroid gland is T4, but T3 causes most of the effects – T4 is converted to T3 by the liver, kidneys, and other peripheral tissues

•

General function of T3/T4: ↑ the metabolic rate of its target cells (which are most cells in the body) –

See Table 18-3 for more specific, FYI effects

Fig. 18-11a, p. 628

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Regulation of thyroid hormone secretion

Fig. 18-11b, p. 628

The parathyroid glands

• There are usually 2 pairs of them embedded in the posterior of the thyroid gland • Most of the cells (the little purple dots in the figure above) are parathyroid (chief) cells – which make parathyroid hormone (PTH) Fig. 18-12, p. 630

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A summary of the hormones secreted by the thyroid and parathyroid glands

Table 18-4, p. 632

• •

•

Calcitonin (CT) ↓ blood [Ca2+] specifically by 1) inhibiting osteoclasts in osseous tissue (while osteoblasts continue to put Ca 2+ into new bone matrix), and 2) stimulating Ca2+ excretion by the kidneys Parathyroid hormone (PTH) ↑ blood [Ca2+] specifically by 1) ↑ the number and activity of osteoclasts, 2) stimulating Ca2+ reabsorption by the kidneys, and 3) stimulating the production of calcitriol (active vitamin D3) by the kidneys, which ↑ the absorption of Ca2+ from the digestive tract CT appears to be most important in childhood, late pregnancy, and during prolonged starvation – Its physiological significance in healthy adults is unclear (PTH is the dominant hormone that regulates blood [Ca2+] in adults)

Blood [Ca2+] homeostasis • Remember, PTH is the dominant blood [Ca2+] regulator in healthy adults (see also Table 18-4 and your hormone chart)

Fig. 18-13, p. 631

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Fig. 18-14, p. 633

The adrenal (suprarenal) glands • •

Are located on top of the kidneys Have 2 main parts: – 1. The adrenal medulla (the inner part) – secretes epinephrine (E) and norepinephrine (NE) – 2. The adrenal cortex (the outer part) – secretes corticosteroids • There are 3 distinct regions or zones in the cortex (see the next slide)

The adrenal cortex • From superficial to deep, the distinct region/zones of the cortex are the zona glomerulosa, zona fasciculata, and zona reticularis • Each distinct region/zone secretes different specific steroid hormones (see the next slide) Fig. 18-14, p. 633

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The adrenal hormones

Fig. 18-14, p. 633

The renin-angiotensin-aldosterone system (RAAS)

Fig. 18-19b, p. 641

19

Additional adrenal hormone notes • Glucocorticoids – Their main overall effect is to cope with chronic (longer-term) emotional, mental, and/or physical stresses • Compare this to sympathetic activation and the adrenal medullae that help to cope with acute (shorter-term) stresses, threats, and/or crises • Essentially, they make sure there is fuel available (especially glucose for the brain) to make enough energy to deal with longer-term stresses

– They also have anti-inflammatory effects, which may help a person cope with stress, but they can also slow tissue repair and depress the immune response!

• Adrenal androgens (male sex hormones) – Small quantities are produced in both males and females – In both males and females, some of these are converted to estrogens (the dominant female sex hormones) – They’re not important in adult males, but in adult females they ↑ muscle and bone mass, blood cell formation, and sex drive

• Epinephrine (E) (a.k.a. adrenaline) and norepinephrine (NE) (a.k.a. noradrenaline) – 75-80% of what the adrenal medullae secrete is E; the rest is NE – As discussed in Ch. 16, their general effect is to enhance and prolong sympathetic activation (the “fight or flight” response)

The pancreas • = a mixed gland located inferior and posterior to the stomach: – Its exocrine portion (which makes up ~ 99% of its volume) = pancreatic acini (and their ducts), which secrete pancreatic juice that contains digestive enzymes and buffers (more details in Ch. 24) – Its endocrine portion = pancreatic islets (islets of Langerhans)

Fig. 18-16, p. 635

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Hormones produced by pancreatic islets

; decreases blood glucose concentrations

Table 18-5, p. 639

FYI

• Insulin also ↑ glucose utilization, ATP generation, amino acid absorption, and protein synthesis (see the next slide) • For somatostatin (which is identical to GH-IH) and pancreatic polypeptide (PP), just know which pancreatic islet cells they’re secreted by, and that in general they have an overall inhibitory effect on digestive function

The specific effects of insulin

Fig. 18-17, p. 636

21

The specific effects of glucagon

Fig. 18-17, p. 636

Other endocrine tissues • Adipose tissue produces a peptide hormone called leptin – Stimulus for secretion: when adipose tissue absorbs lipids and glucose – Target: the hypothalamus – Effects: suppresses appetite; allows normal levels of GnRH and gonadotropin synthesis

• We will discuss the hormones released by organs of other body systems (e.g. the intestines, kidneys, heart, thymus, and gonads) when we cover those other systems

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