Ch30.pdf

UNIT

Eight

Alterations in the

Endocrine System

CHAPTER

Organization and Control

of the Endocrine System

T he endocrine system is involved in all of the integrative

The Endocrine System

Hormones

Paracrine and Autocrine Actions

Eicosanoids and Retinoids

Structural Classiﬁcation

Synthesis and Transport

Metabolism and Elimination

Mechanisms of Action

Control of Hormone Levels

Hypothalamic-Pituitary Regulation

Feedback Regulation

Diagnostic Tests

Blood Tests

Urine Tests

Stimulation and Suppression Tests

Genetic Tests

Imaging

aspects of life, including growth, sex differentiation,

metabolism, and adaptation to an ever-changing en-

vironment. This chapter focuses on general aspects of endo-

crine function, organization of the endocrine system, hormone

receptors and hormone actions, and regulation of hormone

levels.

THE ENDOCRINE SYSTEM

The endocrine system uses chemical substances called hor-

mones as a means of regulating and integrating body func-

tions. The endocrine system participates in the regulation of

digestion, use, and storage of nutrients; growth and develop-

ment; electrolyte and water metabolism; and reproductive

functions. Although the endocrine system once was thought

to consist solely of discrete endocrine glands, it is now known

that a number of other tissues release chemical messengers that

modulate body processes. The functions of the endocrine sys-

tem are closely linked with those of the nervous system and

the immune system. For example, neurotransmitters such as

epinephrine can act as neurotransmitters or as hormones. The

functions of the immune system also are closely linked with

those of the endocrine system. The immune system responds

to foreign agents by means of chemical messengers (cyto-

kines, e.g. , interleukins, interferons) and complex receptor

mechanisms (see Chapter 8). The immune system also is ex-

tensively regulated by hormones such as the adrenal cortico-

steroid hormones.

529

530

Unit Eight: Alterations in the Endocrine System

Hormones

Hormones generally are thought of as chemical messengers

that are transported in body ﬂuids. They are highly specialized

organic molecules produced by endocrine organs that exert

their action on speciﬁc target cells. Hormones do not initiate

reactions; they are modulators of systemic and cellular re-

sponses. Most hormones are present in body ﬂuids at all times

but in greater or lesser amounts, depending on the needs of

the body.

A characteristic of hormones is that a single hormone can

exert various effects in different tissues or, conversely, a single

function can be regulated by several hormones. For example,

estradiol, which is produced by the ovary, can act on the ovar-

ian follicles to promote their maturation, on the uterus to stim-

ulate its growth and maintain the cyclic changes in the uterine

mucosa, on the mammary gland to stimulate ductal growth, on

the hypothalamic-pituitary system to regulate the secretion of

gonadotropins and prolactin, and on general metabolic pro-

cesses to affect adipose tissue distribution. Lipolysis, which is

the release of free fatty acids from adipose tissue, is an example

of a single function that is regulated by several hormones, in-

cluding the catecholamines, glucagon, and secretin. Table 30-1

lists the major functions and sources of body hormones.

pancreatic beta cells can inhibit its release from the same cells.

Juxtacrine refers to a mechanism whereby a cytokine that is em-

bedded in, bound to, or associated with the plasma membrane

of one cell interacts with a speciﬁc receptor in a juxtaposed cell.

Eicosanoids and Retinoids

A group of compounds that have a hormone-like action are

the eicosanoids, which are derived from polyunsaturated fatty

acids in the cell membrane. Among these, arachidonic acid is

the most important and abundant precursor of the various

eicosanoids. The most important of the eicosanoids are the

prostaglandins, leukotrienes, and thromboxanes. These fatty

acid derivatives are produced by most body cells, are rapidly

cleared from the circulation, and are thought to act mainly by

paracrine and autocrine mechanisms. Eicosanoid synthesis

often is stimulated in response to hormones, and they serve as

mediators of hormone action. Retinoids ( e.g. , retinoic acid)

also are derived from fatty acids and have an important role in

regulating nuclear receptor action.

Structural Classiﬁcation

Hormones have diverse structures, ranging from single amino

acids to complex proteins and lipids. Hormones usually are

divided into four categories according to their structures:

(1) amines and amino acids; (2) peptides, polypeptides, glyco-

proteins, and proteins; (3) steroids; and (4) fatty acid deriva-

tives (Table 30-2). The first category, the amines, includes

norepinephrine and epinephrine, which are derived from a

single amino acid ( i.e. , tyrosine), and the thyroid hormones,

which are derived from two iodinated tyrosine amino acid

residues. The second category, the peptides, polypeptides,

glycoproteins, and proteins, can be as small as thyrotropin-

releasing hormone (TRH), which contains three amino acids,

and as large and complex as growth hormone (GH) and

follicle-stimulating hormone (FSH), which have approxi-

mately 200 amino acids. Glycoproteins are large peptide hor-

mones associated with a carbohydrate ( e.g. , FSH). The third

category comprises the steroid hormones, which are deriva-

tives of cholesterol. The fourth category, the fatty acid deriva-

tives, includes the eicosanoids and retinoids.

Paracrine and Autocrine Actions

In the past, hormones were described as chemical substances

that were released into the bloodstream and transported to dis-

tant target sites, where they exerted their action (Fig. 30-1).

Although many hormones travel by this mechanism, some hor-

mones and hormone-like substances never enter the blood-

stream but instead act locally in the vicinity in which they are

released. When they act locally on cells other than those that

produced the hormone, the action is called paracrine . The ac-

tion of sex steroids on the ovary is a paracrine action. Hor-

mones also can exert an autocrine action on the cells from which

they were produced. For example, the release of insulin from

KEY CONCEPTS

HORMONES

Synthesis and Transport

The mechanisms for hormone synthesis vary with hormone

structure. Protein and peptide hormones are synthesized and

stored in granules or vesicles in the cytoplasm of the cell until

secretion is required. The lipid-soluble steroid hormones are re-

leased as they are synthesized.

Protein and peptide hormones are synthesized in the rough

endoplasmic reticulum in a manner similar to the synthesis

of other proteins (see Chapter 1). The appropriate amino acid

sequence is dictated by messenger RNAs from the nucleus.

Usually, synthesis involves the production of a precursor hor-

mone, which is modiﬁed by the addition of peptides or sugar

units. These precursor hormones often contain extra peptide

units that ensure proper folding of the molecule and insertion

of essential linkages. If extra amino acids are present, as in in-

sulin, the precursor hormone is called a prohormone. After

synthesis and sequestration in the endoplasmic reticulum, the

protein and peptide hormones move into the Golgi complex,

where they are packaged in granules or vesicles. It is in the

Golgi complex that prohormones are converted into hormones.

Hormones function as chemical messengers, moving

through the blood to distant target sites of action, or

acting more locally as paracrine or autocrine mes-

sengers that incite more local effects.

■

Most hormones are present in body ﬂuids at all

times but in greater or lesser amounts, depending

on the needs of the body.

■

Hormones exert their actions by interacting with

high-afﬁnity receptors, which in turn are linked to

one or more effector systems in the cell. Some hor-

mone receptors are located on the surface of the cell

and act through second messenger mechanisms,

and others are located in the cell, where they modu-

late the synthesis of enzymes, transport proteins, or

structural proteins.

■

531

Chapter 30: Organization and Control of the Endocrine System

Major Action and Source of Selected Hormones

TABLE 30-1

Source

Hormone

Major Action

Hypothalamus

Releasing and inhibiting hormones

Corticotropin-releasing hormone (CRH)

Thyrotropin-releasing hormone (TRH)

Growth hormone-releasing hormone

(GHRH)

Gonadotropin-releasing hormone (GnRH)

Growth hormone (GH)

Controls the release of pituitary hormones

Anterior pituitary

Stimulates growth of bone and muscle, promotes protein syn-

thesis and fat metabolism, decreases carbohydrate metabolism

Stimulates synthesis and secretion of adrenal cortical hormones

Stimulates synthesis and secretion of thyroid hormone

Female: stimulates growth of ovarian follicle, ovulation

Male: stimulates sperm production

Female: stimulates development of corpus luteum, release of

oocyte, production of estrogen and progesterone

Male: stimulates secretion of testosterone, development of inter-

stitial tissue of testes

Increases water reabsorption by kidney

Stimulates contraction of pregnant uterus, milk ejection from

breasts after childbirth

Increases sodium absorption, potassium loss by kidney

Affects metabolism of all nutrients; regulates blood glucose

levels, affects growth, has anti-inﬂammatory action, and

decreases effects of stress

Have minimal intrinsic androgenic activity; they are converted to

testosterone and dihydrotestosterone in the periphery

Serve as neurotransmitters for the sympathetic nervous system

Adrenocorticotropic hormone (ACTH)

Thyroid-stimulating hormone (TSH)

Follicle-stimulating hormone (FSH)

Luteinizing hormone (LH)

Posterior pituitary

Antidiuretic hormone (ADH)

Oxytocin

Adrenal cortex

Mineralocorticosteroids, mainly aldosterone

Glucocorticoids, mainly cortisol

Adrenal androgens, mainly dehydroepiandros-

terone (DHEA) and androstenedione

Epinephrine

Norepinephrine

Thyroid hormones: triiodothyronine (T 3 ),

thyroxine (T 4 )

Adrenal medulla

Thyroid

(follicular cells)

Increase the metabolic rate; increase protein and bone turnover;

increase responsiveness to catecholamines; necessary for fetal

and infant growth and development

Lowers blood calcium and phosphate levels

Regulates serum calcium

Lowers blood glucose by facilitating glucose transport across cell

membranes of muscle, liver, and adipose tissue

Increases blood glucose concentration by stimulation of

glycogenolysis and glyconeogenesis

Delays intestinal absorption of glucose

Stimulates calcium absorption from the intestine

Affects development of female sex organs and secondary sex

characteristics

Inﬂuences menstrual cycle; stimulates growth of uterine wall;

maintains pregnancy

Affect development of male sex organs and secondary sex

characteristics; aid in sperm production

Thyroid C cells

Parathyroid glands

Pancreatic islet cells

Calcitonin

Parathyroid hormone

Insulin

Glucagon

Somatostatin

1,25-Dihydroxyvitamin D

Estrogen

Kidney

Ovaries

Progesterone

Testes

Androgens, mainly testosterone

Steroid hormones are synthesized in the smooth endoplas-

mic reticulum, and steroid-secreting cells can be identiﬁed by

their large amounts of smooth endoplasmic reticulum. Certain

steroids serve as precursors for the production of other hor-

mones. For example, in the adrenal cortex, progesterone and

other steroid intermediates are enzymatically converted into

aldosterone, cortisol, or androgens (see Chapter 31).

Hormones that are released into the bloodstream circulate

as either free, unbound molecules or as hormones attached to

transport carriers (Fig. 30-2). Peptide hormones and protein

hormones usually circulate unbound in the blood. Steroid

hormones and thyroid hormone are carried by speciﬁc carrier

proteins synthesized in the liver. The extent of carrier binding

influences the rate at which hormones leave the blood and

enter the cells. The half-life of a hormone—the time it takes for

the body to reduce the concentration of the hormone by one

half—is positively correlated with its percentage of protein

binding. Thyroxine, which is more than 99% protein bound,

has a half-life of 6 days. Aldosterone, which is only 15%

bound, has a half-life of only 25 minutes. Drugs that compete

with a hormone for binding with transport carrier molecules

increase hormone action by increasing the availability of the

active unbound hormone. For example, aspirin competes with

thyroid hormone for binding to transport proteins; when the

532

Unit Eight: Alterations in the Endocrine System

Hormone

secretion

Endocrine gland (thyroid)

Carrier-

bound

hormone

Free

hormone

Endocrine

cell

Circulation

Hormone

receptor

Distant target cell

Biological

effects

■ FIGURE 30-2 ■ Relationship of free and carrier-bound hormone.

Paracrine

form. Hormones secreted by endocrine cells must be inacti-

vated continuously to prevent their accumulation. Intracellular

and extracellular mechanisms participate in the termination of

hormone function. Some hormones are enzymatically inacti-

vated at receptor sites where they exert their action. The cate-

cholamines, which have a very short half-life, are degraded by

catechol-O-methyl transferase (COMT) and monoamine oxi-

dase (MAO). Because of their short half-life, their production is

measured by some of their metabolites. In general, peptide hor-

mones also have a short life span in the circulation. Their major

mechanism of degradation is through binding to cell surface re-

ceptors, with subsequent uptake and degradation by enzymes

in the cell membrane or inside the cell. Peptide hormones have

a short life span and are inactivated by enzymes that split pep-

tide bonds. Steroid hormones are bound to protein carriers for

transport and are inactive in the bound state. Their activity de-

pends on the availability of transport carriers. Unbound adre-

nal and gonadal steroid hormones are conjugated in the liver,

which renders them inactive, and then excreted in the bile or

urine. Thyroid hormones also are transported by carrier mole-

cules. The free hormone is rendered inactive by the removal of

amino acids ( i.e. , deamination) in the tissues, and the hormone

is conjugated in the liver and eliminated in the bile.

Paracrine cell

Nearby

target cell

Autocrine

Autocrine cell

■ FIGURE 30-1 ■ Examples of endocrine ( A ), paracrine ( B ), and

autocrine ( C ) secretions.

drug is administered to persons with excessive levels of circu-

lating thyroid hormone, such as during thyroid crisis, serious

effects may occur.

Metabolism and Elimination

Metabolism of hormones and their precursors can generate

more or less active products or it can degrade them to inactive

forms. In some cases, hormones are eliminated in the intact

Classes of Hormones Based on Structure

TABLE 30-2

Fatty Acid

Amines and Amino Acids

Peptides, Polypeptides, and Proteins

Steroids

Compounds

Dopamine

Epinephrine

Norepinephrine

Thyroid hormone

Corticotropin-releasing hormone (CRH)

Growth hormone–releasing hormone (GHRH)

Thyrotropin-releasing hormone (TRH)

Adrenocorticotropic hormone (ACTH)

Follicle-stimulating hormone (FSH)

Luteinizing hormone (LH)

Thyroid-stimulating hormone (TSH)

Growth hormone (GH)

Antidiuretic hormone (ADH)

Oxytocin

Insulin

Glucagon

Somatostatin

Calcitonin

Parathyroid hormone

Aldosterone

Glucocorticoids

Estrogens

Testosterone

Progesterone

Androstenedione

1,25-Dihydroxyvitamin D

Dihydrotestosterone (DHT)

Dehydroepiandrosterone (DHEA)

Eicosanoids

Retinoids

1 LINE

533

Chapter 30: Organization and Control of the Endocrine System

Mechanisms of Action

Hormones produce their effects through interaction with high-

afﬁnity receptors, which in turn are linked to one or more ef-

fector systems within the cell. These mechanisms involve many

of the cell’s metabolic activities, ranging from ion transport at

the cell surface to stimulation of nuclear transcription of com-

plex molecules. The rate at which hormones react depends on

their mechanism of action. The neurotransmitters, which con-

trol the opening of ion channels, have a reaction time of mil-

liseconds. Thyroid hormone, which functions in the control of

cell metabolism and synthesis of intracellular signaling mole-

cules, requires days for its full effect to occur.

CHART 30-1 Hormone–Receptor Interactions

Surface (Second Messenger) Receptors

Glucagon

Insulin

Epinephrine

Parathyroid hormone

Thyroid-stimulating hormone (TSH)

Adrenocorticotropic hormone (ACTH)

Follicle-stimulating hormone (FSH)

Luteinizing hormone (LH)

Antidiuretic hormone (ADH)

Secretin

Receptors. Hormones exert their action by binding to high-

affinity receptors located either on the surface or inside the

target cells. The function of these receptors is to recognize a spe-

ciﬁc hormone and translate the hormonal signal into a cellular

response. The structure of these receptors varies in a manner

that allows target cells to respond to one hormone and not to

others. For example, receptors in the thyroid are specific for

thyroid-stimulating hormone, and receptors on the gonads re-

spond to the gonadotropic hormones.

The response of a target cell to a hormone varies with the

number of receptors present and with the afﬁnity of these recep-

tors for hormone binding. A variety of factors inﬂuence the

number of receptors that are present on target cells and their

afﬁnity for hormone binding.

There are approximately 2000 to 100,000 hormone recep-

tor molecules per cell. The number of hormone receptors on

a cell may be altered for any of several reasons. Antibodies

may destroy or block the receptor proteins. Increased or de-

creased hormone levels often induce changes in the activity of

the genes that regulator receptor synthesis. For example, de-

creased hormone levels often produce an increase in receptor

numbers by means of a process called up-regulation ; this in-

creases the sensitivity of the body to existing hormone levels.

Likewise, sustained levels of excess hormone often bring about

a decrease in receptor numbers by down-regulation , producing

a decrease in hormone sensitivity. In some instances, the re-

verse effect occurs, and an increase in hormone levels appears

to recruit its own receptors, thereby increasing the sensitivity

of the cell to the hormone. The process of up-regulation and

down-regulation of receptors is regulated largely by inducing

or repressing the transcription of receptor genes.

The afﬁnity of receptors for binding hormones also is af-

fected by a number of conditions. For example, the pH of the

body ﬂuids plays an important role in the afﬁnity of insulin re-

ceptors. In ketoacidosis, a lower pH reduces insulin binding.

Some hormone receptors are located on the surface of the

cell and act through second messenger mechanisms, and others

are located within the cell, where they modulate the synthesis

of enzymes, transport proteins, or structural proteins. The re-

ceptors for thyroid hormones, which are found in the nucleus,

are thought to be directly associated with controlling the ac-

tivity of genes located on one or more of the chromosomes.

Chart 30-1 lists hormones that act through the two types of

receptors.

Intracellular Interactions

Estrogens

Testosterone

Progesterone

Adrenal cortical hormones

Thyroid hormones

cites the generation of an intracellular signal or message. The

intracellular signal system is termed the second messenger , and

the hormone is considered to be the ﬁrst messenger (Fig. 30-3).

For example, the ﬁrst messenger glucagon binds to surface re-

ceptors on liver cells to incite glycogen breakdown by way of

the second messenger system.

The most widely distributed second messenger is cyclic

adenosine monophosphate (cAMP). cAMP is formed from

Hormone

Second

messenger

Surface receptor

Enzyme activity

Cell

response

Nucleus

Hormone

Protein

synthesis

Hormone-receptor

complex

Surface Receptors. Because of their low solubility in the lipid

layer of cell membranes, peptide hormones and catechol-

amines cannot readily cross the cell membrane. Instead, these

hormones interact with surface receptors in a manner that in-

■ FIGURE 30-3 ■ The two types of hormone–receptor interactions:

the surface receptor (A) and the intracellular receptor (B) .

LONG

Plik z chomika:

Inne pliki z tego folderu:

Inne foldery tego chomika: