Ch7

Kip McGilliard Eastern Illinois University

Lauralee Sherwood Hillar Klandorf Paul Yancey

Chapter 7 Endocrine Systems

7.1 Introduction: Principles of Endocrinology

Endocrinology is the study of the evolution and physiological function of hormones.

The endocrine system regulates and coordinates distant organs through the secretion of hormones.

Hormones are signal molecules delivered by circulatory fluids.

In contrast to the nervous system, the endocrine system controls activities that require duration rather than speed.


Chemical classes of hormones Peptide and protein hormones

Chains of amino acids Hydrophilic Example: Insulin

Amines Derived from tyrosine Catecholamines (e.g. epinephrine) are hydrophilic Thyroid hormones (e.g. thyroxine) are lipophilic

Steroids Derived from cholesterol Lipophilic Examples: Testosterone and estradiol


Hormone synthesis and secretion Peptide hormones

Synthesized as large precursor proteins, preprohormones

Portions are cleaved and peptide hormone is packaged into secretory vesicles

Released from cell by exocytosis

Steroid hormones Cholesterol is synthesized or obtained from diet Chemically modified by a series of enzymatic

reactions Once synthesized, steroid hormones immediately

diffuse across the plasma membrane

Figure 7-3 p272

Cholesterol

Pregneneolone 17-Hydroxypregneneolone Dehydroepiandrosterone (adrenal cortex hormone)

Progesterone 17-Hydroxyprogesterone Androstenedione Estrone

(female sex hormone)

11-Deoxycorticosterone Deoxycortisol Testosterone Estradiol

Androgens (male sex hormones) Corticosterone

Cortisol Estriol

Aldosterone Glucocorticoid (adrenal cortex

hormone)

Estrogens (female sex hormones) Mineralocorticoid

(adrenal cortex hormone)


Mechanisms of hormone action Hormones are widely distributed, but only target cells

have receptors to respond to each hormone

Peptides and catecholamines bind with membrane receptors Alter the conformation of adjacent ion channels, or Activate second-messenger systems

Steroid and thyroid hormones pass through the plasma membrane and bind with internal receptors Receptors inside the cell are transcription factors that

regulate specific genes Hormone receptor complex binds with hormone

response element (HRE) on nuclear DNA Turns on synthesis of a specific protein

Nucleus

Hormone response element

Gene

Binding activates gene.

DNA

Hormone receptor complex binds with DNAs hormone response element.

Activated gene transcribes mRNA.

mRNA

New mRNA leaves nucleus.

Ribosomes read mRNA to synthesize new proteins.

New protein is released from ribosome and processed into final folded form.

New protein brings about desired response.

New protein

Cellular response

DNA-binding site (active)

Hormone binds with intracellular receptor specific for it.

Portion that binds hormone

Free lipophilic hormone diffuses though plasma membrane

Steroid hormone

Plasma protein carrier

Blood vessel

Steroid hormone receptor Portion

that binds to DNA

ECF

Cytoplasm

Plasma membrane

1

2

3

4

5

6

7

8

9

Figure 7-4 p274


Regulation of plasma concentration of hormones Negative feedback control

When plasma hormone levels fall, hormone secretion is stimulated

Neuroendocrine reflexes Produce a sudden increase in hormone secretion in

response to a specific stimulus

Biological rhythms Secretion of most hormones rhythmically fluctuates

as a function of time (biological clocks) Readjustment of set point by CNS Example: Cortisol secretion rises at night to peak

in early morning (diurnal rhythm)


Endocrine disorders Hyposecretion -- inadequate secretion of a hormone

Primary hyposecretion -- abnormality within the gland Secondary hyposecretion -- deficiency of tropic

hormones

Hypersecretion -- excessive secretion of a hormone Primary or secondary

Endocrine-disrupting chemicals (EDCs) Human-made substances released into the environment

that mimic or oppose the actions of hormones Example: DDE and DDT act as anti-androgens in

mammals

7.2 Nonvertebrate Endocrinology

Growth and molting in insects Ecdysone is secreted by the prothoracic glands

Secretion of ecdysone is stimulated by prothoracotropic hormone (PTTH) secreted by neurosecretory cells in brain

Ecdysone initiates the molting process

Juvenile hormone (JH) is secreted by the corpora allata JH assures that larval characteristics are retained JH levels progressively decline at each larval stage

Ecdysone in the absence of JH enables metamorphosis to the adult form

7.2 Nonvertebrate Endocrinology

Figure 7-7 p280

Stimuli (related to feeding activities)

anterior end of larva Hormone secretory cells in brain

Juvenile hormone Brain

hormone Corpus allatum 1 2 3 4

Prothoracic gland

ecdysone ecdysone

Changing blood concentrations of hormones

Larval stages Pupa Adult

7.3 Vertebrate Endocrinology: Central Endocrine Glands

Figure 7-1 p269

Pineal Hypothalamus Pituitary

Parathyroid Thyroid

Thymus

Heart

Stomach Adrenal gland Pancreas Duodenum Kidney

Skin Ovaries in female Placenta in pregnant female

Testes in male

ANIMATION: Major human endocrine glands

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Pineal gland Secretes melatonin Maintains circadian rhythms

Melatonin secretion increases up to 10-fold in darkness

Seasonal changes in melatonin secretion patterns trigger reproduction

In mammals melatonin output is controlled by the suprachiasmatic nucleus (SCN) of the hypothalamus SCN receives light information from the eyes

Figure 7-8 p282

Pineal gland

Photoperiod Retina Anestrous Breeding Melatonin

SCN Kisspeptin neuron GnRH

Pituitary

LH pulse Frequency

Estradiol feedback

Follicle

Ovary


Pituitary gland (hypophysis) Located at the base of the brain, connected to the

hypothalamus by a thin stalk, the infundibulum

Posterior pituitary (neurohypophysis) Nervous tissue

Anterior pituitary (adenohypophysis) Glandular epithelial tissue

Intermediate lobe (pars intermedia) Absent in birds and cetaceans Rudimentary in humans after birth Size of intermediate lobe correlates with ability of

animal to adapt to coloration of its environment

Figure 7-9a p285

Bone

Hypothalamus

Anterior lobe of pituitary

Posterior lobe of pituitary

(a) Relation of pituitary gland to hypothalamus and rest of brain

Posterior pituitary

Anterior pituitary

(b) Enlargement of pituitary gland and its connection to hypothalamus

Optic chiasm Connecting stalk

Hypothalamus

Figure 7-9b p285


Intermediate lobe Secretes melanocyte-stimulating hormone (MSH)

-MSH controls skin coloration via dispersion of storage granules containing melanin

In lower vertebrates, -MSH is opposed by melanin-concentrating hormone (MCH)

Melanocortin-1 receptor (MC1R) determines skin color, pelage and feather pigmentation in animals lacking pars intermedia

Excessive MSH secretion darkens human skin

MSH reduces appetite and suppresses immune system


Posterior pituitary Connects to the hypothalamus by a neural

pathway Neurosecretory neurons have cell bodies in

supraoptic and paraventricular nuclei of hypothalamus

Axons terminate on capillaries in posterior pituitary

Secretes vasopressin and oxytocin Evolutionary precursor, arginine vasotocin,

is found in many vertebrates


Posterior pituitary hormones Vasopressin

Enhances retention of water by kidneys (antidiuretic effect)

Causes contraction of arteriolar smooth muscle (vasoconstriction)

Oxytocin Social bonding Contraction of uterine smooth muscle Ejection of milk from mammary glands

Arginine vasotocin Involved in osmoregulation Vasoconstriction

Figure 7-10 p286

Supraoptic nucleus

Neurosecretory neuronal cell bodies in hypothalamus (produce vasopressin and oxytocin)

1

Hypothalamus

Paraventricular nucleus

Axons

Hypothalamic posterior- pituitary stalk

Neuronal terminals in posterior pituitary (release vasopressin and oxytocin into systemic blood)

Capillary

Anterior pituitary

Posterior pituitary

Systemic venous blood out Systemic

arterial blood in

Vasopressin Oxytocin

Figure 7-10 p286

Vasopressin Oxytocin

Nephrons in kidneys

Arterioles throughout body

Uterus Mammary glands

Increases permeability of distal and collecting tubules to H2O

Causes vasoconstriction

Stimulates uterine contractions

Stimulates milk ejection during breast- feeding


Anterior pituitary hormones Growth hormone (GH, somatotropin)

Stimulates growth and affects metabolism Thyroid-stimulating hormone (TSH, thyrotropin)

Stimulates thyroid hormone secretion by thyroid gland Adrenocorticotropic hormone (ACTH, corticotropin)

Stimulates cortisol secretion by the adrenal cortex Follicle-stimulating hormone (FSH)

Regulates gamete production Luteinizing hormone (LH)

Regulates sex hormone secretion Ovulation and formation of corpus luteum in females

Prolactin (PRL) Stimulates milk production by mammary glands Wide range of additional actions

Hypothalamus

Anterior pituitary Posterior pituitary

Increased metabolic rate

Thyroid hormone (T3 and T4)

Thyroid gland

TSH

Metabolic actions; stress response

ACTH

Adrenal cortex

Cortisol Breast growth and milk secretion

Mammary glands

Prolactin

Growth hormone

Liver

IGF-I

Bone

Growth

Soft tissues

Metabolic actions

Sex hormone secretion (estrogen and progesterone in females, testosterone in males)

Gamete production (ova in females, sperm in males)

(ovaries in females)

Gonads (testes in males)

LH FSH Adipose tissue, muscle, liver

Figure 7-11 p287

ANIMATION: Anterior pituitary function




Hypothalamic releasing and inhibiting hormones Secretion of each anterior pituitary hormone is

regulated by hypothalamic hypophysiotropic hormones

Thyrotropin-releasing hormone (TRH) Corticotropin-releasing hormone (CRH) Gonadotropin-releasing hormone (GnRH)

stimulates release of FSH and LH Growth hormone-releasing hormone (GHRH) Growth hormone-inhibiting hormone (GHIH,

somatostatin) Prolactin-releasing hormone (PRH) Prolactin-inhibiting hormone (PIH)


Hypothalamic releasing and inhibiting hormones

Releasing and inhibiting hormones reach the anterior pituitary through the hypothalamic-hypophyseal portal system

Regulation of hypophysiotropic hormone secretion

Neural input (e.g. CRH secretion in response to stress)

Negative-feedback effects of anterior pituitary or target gland hormones (e.g. cortisol levels above a set point inhibit CRH and ACTH secretion)

Systemic venous blood out

Anterior pituitary

Posterior pituitary

Hypothalamic- hypophyseal portal system

Releasing and inhibiting hormones Systemic

arterial blood in

Capillaries in anterior pituitary

Endocrine cells of anterior pituitary (secrete anterior pituitary hormones into systemic blood)

Capillaries in hypothalamus

Hypothalamus

Neurosecretory neurons in hypothalamus (secrete releasing and inhibiting hormones into portal system)

= Hypophysiotropic hormones = Anterior pituitary hormone KEY

1

2

3

4 5

6

1

Figure 7-13 p289

7.4 Endocrine Control of Growth and Development in Vertebrates

Growth depends on: Adequate diet

Malnourished animals do not reach full growth potential

Seasonally shortened day length reduces growth by reducing food intake

Freedom from chronic disease and stressful environmental conditions Glucocorticoids secreted during stress inhibit

growth

Growth-influencing hormones Placental hormones promote fetal growth Growth hormone and other hormones promote

growth after birth


Direct effects of growth hormone (GH) Metabolic effects

Target organs are adipose tissue, skeletal muscles and liver

Mobilizes fat stores as a major energy source Conserves glucose for use by the brain

Decreases glucose uptake by muscles and increases glucose output by the liver

Enhances immune system GHs growth-promoting actions are mediated by

insulin-like growth factors (IGFs)


GH/IGFs growth promoting effects Growth of soft tissues

Increases number of cells (hyperplasia) Increases size of cells (hypertrophy) Promotes uptake of amino acids into cells Stimulates protein synthesis and inhibits protein

degradation

Growth of bone Promotes increases in bone thickness and length Thickness depends on addition of new bone by

osteoblasts Length depends on proliferation of cartilage cells

(chondrocytes) in epiphyseal plates and invasion by osteoblasts

Figure 7-14a p294

Articular cartilage

Bone of epiphysis

Epiphyseal plate

Bone of diaphysis

Marrow cavity

(a) Anatomy of a long bone

Figure 7-14b p294

Bone of epiphysis Bone of epiphysis Chondrocytes

1 undergo cell division. Resting

chondrocytes Causes thickening of epiphyseal plate

The 2 older chondrocytes grow larger.

Epip

hyse

al p

late

As the extracellular matrix calcifies, the entrapped chondrocytes die. The dead chondrocytes are cleared away by osteoclasts.

Osteoblasts swarm up from diaphysis and deposit bone over persisting remnants of disintegrating cartilage. D

iaph

ysis

(b) Two sections of the same epiphyseal plate at different times, depicting the lengthening of long bones


Regulation of growth hormone secretion Negative feedback loop involving hypothalamus-

pituitary-liver axis IGF-I inhibits secretion of GH by somatotropes in

anterior pituitary IGF-I inhibits GHRH-secreting cells and stimulates

somatostatin-secreting cells in hypothalamus

Other stimuli to GH secretion Onset of sleep Exercise, stress, and hypoglycemia High protein meal Ghrelin

Figure 7-14b p294

Bone of epiphysis Bone of epiphysis Chondrocytes

1 undergo cell division. Resting

chondrocytes Causes thickening of epiphyseal plate

The 2 older chondrocytes grow larger.

Epip

hyse

al p

late

As the extracellular matrix calcifies, the entrapped chondrocytes die. The dead chondrocytes are cleared away by osteoclasts.

Osteoblasts swarm up from diaphysis and deposit bone over persisting remnants of disintegrating cartilage. D

iaph

ysis

(b) Two sections of the same epiphyseal plate at different times, depicting the lengthening of long bones


Growth hormone administration Increases bone growth Treatment of dwarfism in humans

Increases muscle mass Abuse by athletes Improved meat production in swine

Increases milk production in dairy cattle

7.5 Thyroid Gland

Thyroid gland is located in the throat below the larynx

Composed of follicular cells arranged in fluid-filled spheres (thyroid follicles)

Colloid serves as an extracellular storage site for thyroid hormones in the form of thyroglobulin, a large glycoprotein

7.5 Thyroid Gland

Figure 7-16a p298

Thyroid gland

Right lobe Trachea Isthmus Left lobe

(a) Gross anatomy of thyroid gland

Figure 7-16b p298

Follicular cell Colloid C cell

(b) Light-microscopic appearance of thyroid gland

7.5 Thyroid Gland

Thyroid hormone synthesis 1. Thyroglobulin (Tg) is synthesized by thyroid

follicular cells (incorporating tyrosine) and secreted into colloid by exocytosis

2. Thyroid follicular cells efficiently capture iodide (I-), obtained from the diet, using an iodide pump

3. Iodide is activated and attached to tyrosine molecules on Tg in colloid Monoiodotyrosine (MIT) has one iodine Diiodotyrosine (DIT) has two iodines

7. Iodinated tyrosines couple to form tetraiodothyronine (T4, thyroxine) and triiodothyronine (T3)

7.5 Thyroid Gland

Secretion of thyroid hormones 1. Follicular cells take up a piece of colloid (containing

iodinated Tg) by phagocytosis

2. Lysosomal enzymes split off T4, T3, MIT and DIT in the process of breaking down Tg

3. T4 and T3 (biologically active thyroid hormones) diffuse across follicular cell membrane into blood, while MIT and DIT are recycled to iodide and tyrosine

7.5 Thyroid Gland

Thyroid follicle

2 DITs

DIT

Colloid

Blood

I

Endoplasmic reticulum

Golgi complex

Thyroid follicular cell

I

Lysosome

MIT Tg

1 MIT + 1 DIT DIT

I

DIT MIT

MIT

I

I

Tg

DIT MIT

T4 T4 T4 T4

T4 T3

T3 T3

T3

T3

1

2

3

4a 4b

5a 5b 6

7 8a

8b

Figure 7-17 p299

7.5 Thyroid Gland

Mechanism of thyroid hormone action T3 is the major biologically active form of

thyroid hormone

Most secreted T4 is activated by conversion to T3 by a deiodinase enzyme

T3 binds with nuclear receptors attached to thyroid-response elements of DNA

Alters transcription of specific mRNAs and synthesis of specific proteins

7.5 Thyroid Gland

Effects of thyroid hormones Increase basal metabolic rate (BMR) through

increased mitochondrial and Na+-K+ pump activity Modulate synthesis and degradation of metabolic fuel

molecules Molting in birds and mammals Sympathomimetic effect -- increase target cell

responsiveness to catecholamines Increase heart rate and force of contraction Essential for growth (permissive effect on GH) Development of CNS Metamorphosis in amphibians

7.5 Thyroid Gland

Figure 7-18 p302

Hypothalamus Thyroid gland

TSH TRH

Anterior pituitary

(a) Conversion of thyroxine (+ GH) into triiodothyronine

1 day

8 days 21 days 27 days 30 days 40 days (b)

7.5 Thyroid Gland

Regulation of thyroid hormone secretion Negative feedback loop involving

hypothalamus-pituitary-thyroid axis

Thyroid-stimulating hormone (TSH) stimulates almost every step of thyroid hormone synthesis and secretion

Hypothalamic thyrotropin-releasing hormone (TRH) stimulates TSH secretion by thyrotropes in anterior pituitary

Elevated T3 and T4 levels inhibit TSH secretion

Other factors affecting thyroid hormone secretion Stress inhibits TSH secretion Cold stimulates TSH secretion (infants)

7.5 Thyroid Gland

Metabolic rate and heat production; enhancement of growth and CNS development; enhancement of sympathetic activity

Thyroid hormone (T3 and T4)

Thyroid gland

Thyroid-stimulating hormone (TSH)

Thyrotropin-releasing hormone (TRH)

Anterior pituitary

Hypothalamus

Stress Cold in infants

Figure 7-19 p303

7.5 Thyroid Gland

Abnormalities of thyroid function

Hypothyroidism -- low thyroid activity Causes

Primary failure of thyroid gland or Secondary to a deficiency of TSH (or TRH) or Inadequate dietary supply of iodine

Symptoms stem from reduced metabolic activity (e.g. weight gain, fatigue, poor tolerance of cold)

Hyperthyroidism -- elevated thyroid activity Symptoms stem from increased metabolic activity

(e.g. weight loss, increased heart rate, anxiety)

7.6 Adrenal Glands

Adrenal glands are located above the kidneys Outer adrenal cortex is composed of

steroidogenic cells of mesodermal origin

Inner adrenal medulla is composed of chromaffin cells of neural crest origin

Steroidogenic and chromaffin tissues are intermingled in most non-mammalian species

7.6 Adrenal Glands

Steroid hormones of the adrenal cortex Derived from cholesterol

Modified by stepwise enzymatic reactions

Mineralocorticoids (e.g. aldosterone) Influence mineral (electrolyte) balance Produced in zona glomerulosa

Glucocorticoids (e.g. cortisol) Role in metabolism of glucose, proteins and lipids Produced in zona fasciculata

Sex steroids (e.g. dehydroepiandrosterone) Androgenic (masculinizing) effects Produced in zona fasciculata and zona reticularis

7.6 Adrenal Glands

Figure 7-20a p305

Adrenal cortex Adrenal medulla

Adrenal gland

Kidney

(a) Location and gross structure of adrenal glands

Figure 7-20b p305

Connective tissue capsule

Mineralcorticoids Zona glomerulosa

Zona fasciculata

Glucocorticoids (sex hormones)

Cortex

Zona reticularis

Medulla Catecholamines

(b) Layers of adrenal cortex

7.6 Adrenal Glands

Figure 7-3 p272

Cholesterol

Pregneneolone 17-Hydroxypregneneolone Dehydroepiandrosterone (adrenal cortex hormone)

Progesterone 17-Hydroxyprogesterone Androstenedione Estrone

(female sex hormone)

11-Deoxycorticosterone Deoxycortisol Testosterone Estradiol

Androgens (male sex hormones) Corticosterone

Cortisol Estriol

Aldosterone Glucocorticoid (adrenal cortex

hormone)

Estrogens (female sex hormones) Mineralocorticoid

(adrenal cortex hormone)

7.6 Adrenal Glands

Effects of glucocorticoids Metabolic effects -- increase blood glucose,

while reducing protein and fat stores

Permissive actions (e.g. permit catecholamines to induce vasoconstriction)

Enhanced memory Adaptation to long-term stress Anti-inflammatory and immunosuppressive

effects, especially at high doses

7.6 Adrenal Glands

Regulation of glucocorticoid secretion Negative feedback loop involving

hypothalamus-pituitary-adrenal axis

Adrenocorticotropic hormone (ACTH) stimulates cortisol secretion

Hypothalamic corticotropin-releasing hormone (CRH) stimulates ACTH secretion by corticotropes in the anterior pituitary

Elevated glucocorticoid levels inhibit CRH and ACTH secretion

Other factors affecting glucocorticoid secretion Stress stimulates CRH secretion Circadian rhythm

7.6 Adrenal Glands

Metabolic fuels and building blocks available to help resist stress

Blood fatty acids (by stimulating lipolysis)

Blood amino acids (by stimulating protein degradation)

Blood glucose (by stimulating gluconeogenesis and inhibiting glucose uptake)

Cortisol

Adrenal cortex

Adrenocorticotropic hormone (ACTH)

Anterior pituitary

Corticotropin-releasing hormone (CRH)

Hypothalamus

Stress Diurnal rhythm

Figure 7-21 p307

7.6 Adrenal Glands

Abnormalities of adrenocortical function Cushings syndrome -- excessive cortisol secretion

Most common cause -- overstimulation by excess ACTH Consequences of excessive gluconeogenesis

High blood glucose and protein loss Redistribution of fat in humans and dogs

Addisons disease (primary adrenocortical insufficiency) -- deficiency of adrenal steroids

Most common cause -- autoimmune destruction of the adrenal cortex

Aldosterone deficiency can be fatal Cortisol deficiency causes poor response to stress,

hypoglycemia, and lack of permissive actions

7.6 Adrenal Glands

Chromaffin cells in the adrenal medulla are modified postganglionic sympathetic neurons.

Secrete norepinephrine (NE) and epinephrine (ratio varies between species) Both are catecholamines derived from tyrosine Most synthetic steps take place in cytoplasm Stored in chromaffin granules

Secretion is by exocytosis (similar to neurotransmitter secretion)

Secretion is stimulated by the sympathetic system (e.g. during fear or stress)

7.6 Adrenal Glands

Effects of adrenal catecholamines Increased cardiac output and arterial blood

pressure Vasodilation of coronary and skeletal-muscle

arterioles Dilation of respiratory airways Inhibition of digestive activity Mobilization of stored carbohydrates and fat CNS arousal Sweating Dilation of pupils and flattening of lens

7.6 Adrenal Glands

Multifaceted stress response is coordinated by the hypothalamus

Hypothalamus receives input concerning physical and emotional stressors Activates sympathetic nervous system Secretes CRH Secretes vasopressin

Chronic stress responses are detrimental Breakdown of body structures Reproductive failure Increased susceptibility to disease

7.6 Adrenal Glands

7.7 Endocrine Control of Fuel Metabolism in Vertebrates

Metabolism refers to all chemical reactions that occur within body cells.

Anabolism -- synthesis of larger organic molecules from smaller subunits Requires energy in the form of ATP Manufacture of molecules needed by the cell Storage of nutrients

Catabolism -- breakdown of organic molecules into smaller subunits Hydrolysis of large organic macromolecules Oxidation of smaller molecules (e.g. glucose)

to release energy for ATP production


Regulation of metabolic fuels Dietary intake is usually intermittent Absorptive state

After a meal Glucose is plentiful and used as the major energy

source Excess nutrients are stored as glycogen or

triglycerides

Postabsorptive state Between meals (fasting) Endogenous energy stores are mobilized to provide

energy Fatty acids are the major energy source for most

tissues


Pancreas is composed of both exocrine and endocrine tissues

Exocrine portion secretes digestive enzymes through the pancreatic duct into the digestive tract lumen

Islets of Langerhans are integrators of endocrine regulatory responses and secrete hormones

Pancreatic hormones are the dominant hormonal regulators of glucose homeostasis

cells secrete insulin cells secrete glucagon D cells secrete somatostatin F cells secrete pancreatic polypeptide


Effects of insulin Lowers blood glucose and promotes storage of

carbohydrates Facilitates glucose transport into most cells Stimulates glycogenesis in skeletal muscle and liver Inhibits glycogenolysis in liver Inhibits gluconeogenesis in liver

Lowers blood fatty acids and promotes storage of triglycerides Stimulates production of fatty acids from glucose Inhibits lipolysis

Lowers blood amino acids and enhances protein synthesis Promotes uptake of amino acids into cells

Figure 7-24 p317

Factors that increase blood glucose Factors that decrease blood glucose

Transport of glucose into cells: For utilization for energy production For storage *as glycogen through glycogenesis *as triglycerides

Glucose absorption from digestive tract

Blood glucose

Hepatic glucose production: Through glycogenolysis of stored glycogen Through gluconeogenesis

Urinary excretion of glucose (occurs only abnormally, when blood glucose level becomes so high it exceeds the reabsorptive capacity of kidney tubules during urine formation)

ANIMATION: Hormones and glucose metabolism




Regulation of insulin secretion Direct negative-feedback system between

pancreatic cells and the blood glucose level During absorption of a meal, insulin secretion

increases

Other factors that stimulate insulin secretion: Increased blood amino acids Gastrointestinal hormones -- glucose-

independent insulinotropic peptide (GIP), glucagon-like peptide (GLP) Increased parasympathetic activity

Blood glucose Blood fatty acids Blood amino acids Protein synthesis Fuel storage

Insulin secretion

Parasympathetic stimulation

Food intake

Gastrointestinal hormones (incretins)

Major control

Blood glucose concentration

Sympathetic stimulation (and epinephrine)

Islet cells

Blood amino acid concentration

Figure 7-25 p319


Glucagon Effects oppose those of insulin

Increases hepatic glucose production and raises blood glucose levels

Promotes fat breakdown and inhibits triglyceride synthesis, raising fatty acid levels in blood

Promotes protein breakdown in liver, but does not affect muscle protein

Glucagon secretion is increased during the postabsorptive state when blood glucose levels are low

Blood glucose to normal


Glucagon

cell

Insulin

Blood glucose

Glucagon Insulin

cell cell cell

Blood glucose

Figure 7-26 p321

Blood glucose Blood glucose

Glucagon Insulin Glucagon Insulin



a cell b cell a cell b cell

Stepped Art

Figure 7-26 p321


Diabetes mellitus Elevated blood glucose levels (hyperglycemia)

Glucose in the urine attracts water to cause excessive urination

Type I (insulin-dependent) diabetes mellitus Lack of insulin secretion by pancreatic cells Requires administration of insulin

Type II (non-insulin-dependent) diabetes mellitus Insulin levels are normal or elevated Reduced sensitivity of target cells to insulin

7.8 Endocrine Control of Calcium Metabolism in Vertebrates

Importance of calcium In mammals, 99% of calcium (Ca2+) is stored in the

skeleton and teeth Only free Ca2+ in plasma is biologically active and

subject to regulation

Both Ca2+ homeostasis and Ca2+ balance must be regulated

Ca2+ plays a vital role in: Neuromuscular excitability Excitation-contraction coupling in cardiac and smooth

muscle Stimulus-secretion coupling Maintenance of tight junctions between cells Clotting of blood


Parathyroid hormone (PTH) Secreted by the parathyroid glands, located near the

thyroid gland

Essential for life Raises plasma Ca2+ levels

Promotes transfer of Ca2+ from bone fluid into plasma Promotes resorption of bone by osteoclasts Increases reabsorption of Ca2+ in the kidneys Indirectly increases Ca2+ absorption from the small

intestine by activating vitamin D

PTH secretion is increased in response to a fall in plasma Ca2+ levels

Figure 7-30a p328

Osteoblast Osteocytic osteoblastic bone membrane

Osteocyte

Osteoblast

Osteoclast

Mineralized bone

Blood vessel

Outer surface

Central canal

Canaliculi Bone fluid

Lamellae

(a) Osteocyticosteoblastic bone membrane

Figure 7-30b p328

In canaliculi In central canal

Mineralized bone: stable pool of Ca2+

Bone fluid: labile pool of Ca2+

1 Fast exchange

Slow exchange

Ca2+

Plasma

2 Ca2+

(Bone dissolution)

Osteocyticosteoblastic bone membrane (formed by filmy cytoplasmic extensions of interconnected osteocytes and osteoblasts)

(b) Fast and slow exchange of Ca2+ between bone and plasma

PTH Calcitonin

Parathyroid glands Thyroid C cells

Plasma Ca2+ Plasma Ca2+

Plasma Ca2+ Plasma Ca2+

Figure 7-31 p328


Calcitonin Produced by C cells of the mammalian thyroid

gland, ultimobranchial glands in birds, and connective tissue sheets around the heart in fishes

Decreases plasma Ca2+ levels Decreases transfer of Ca2+ from bone fluid into plasma Decreases bone resorption by inhibiting activity of

osteoclasts Ability to lower blood Ca2+ is especially important in

marine fishes because of Ca2+ in sea water

Calcitonin secretion is increased in response to an increase in plasma Ca2+ levels


Vitamin D (cholecalciferol) Produced in skin from 7-dehydrocholesterol

on exposure to sunlight Can also be obtained in the diet

Activated by sequential alterations in the liver and kidneys, forming 1,25-(OH)2-vitamin D3 (calcitriol)

Promotes Ca2+ absorption in the intestine

Increases sensitivity of bone to PTH

Figure 7-32 p329

Precursor in skin (7-dehydrocholesterol) Dietary vitamin D

Sunlight

Vitamin D3

Hydroxyl group (OH)

Liver enzymes

25-OH-vitamin D3

Hydroxyl group

Plasma Ca2+ PTH

Kidney enzymes

Plasma PO43

1,25-(OH)2 -vitamin D3 (active vitamin D)

Promotes intestinal absorption of Ca2+ and PO43

Plasma Ca2+

Urinary excretion of Ca2+

Absorption of Ca2+ in intestine

Intestine

Activation of vitamin D

Renal tubular Ca2+ reabsorption

Kidneys

Mobilization of Ca2+ from bone

Bone

PTH

Parathyroid glands

Plasma Ca2+ Relieves

Enhances responsiveness of bone to PTH

Figure 7-33 p330


Disorders of Ca2+ metabolism Hyperparathyroidism -- excess PTH

secretion Bones, stones, and abdominal groans

Vitamin D deficiency Impaired intestinal absorption of Ca2+ Demineralized bone is soft and deformed Rickets in children; osteomalacia in adults

Excessive demands for Ca2+ Parturient paresis (milk fever) in dairy cattle Egg laying in birds

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