1. Chapter 19 The Peripheral Endocrine Glands

2. Peripheral Endocrine Glands
Thyroid gland controls basal metabolic rate.
Adrenal glands maintain salt balance, involved in nutrient metabolism and stress adaptation.
Endocrine pancreas important in nutrient metabolism and glucose homeostasis.
Parathyroid glands important in Ca2+ metabolism.

3. Thyroid Gland Contains two types of endocrine secretory cells:
follicular cells produce tetraiodothyronine (T4 or thyroxine) and tri-iodothyronine (T3)
C cells produce Ca2+-regulating hormone calcitonin.

4. Thyroid Hormone Synthesis
Basic ingredients:
amino acid tyrosine synthesized in sufficient amounts by body
iodine obtained from dietary intake
Thyroid hormone is synthesized and stored on the thyroglobulin molecule.
Thyroid hormones remain in colloid until they are split off and secreted.
Usually enough thyroid hormone stored to supply body’s needs for several months.

5.  Process forms MIT and DIT.
Thyroid
follicular cell
Blood
Colloid
Golgi
complex 4a 4b
Endoplasmic
reticulum 1 Tg Tg
MIT
DIT 5a 5b 2 3 I–
Na+
Na+
(Iodinase
action) 4 6b K+ K+ 6a
Lysosome
MIT
1 MIT + 1 DIT
2 DITs
DIT 7 9b
MIT
MIT
DIT 8
DIT 9a
Figure 19.2: Synthesis, storage, and secretion of thyroid hormone.
Note that the organelles are not drawn to scale. The endoplasmic reticulum/Golgi complex are proportionally too small.
1 Tyrosine-containing Tg produced within the thyroid follicular cells by the endoplasmic reticulum–Golgi complex is transported by exocytosis into the colloid.
2 Iodide is carried by secondary active transport from the blood into the colloid by symporters in the basolateral membrane of the follicular cells.
3 In the follicular cell, the iodide is oxidized to active form by TPO at the luminal membrane.
4 The active iodide exits the cell through a luminal channel to enter the colloid.
5a Catalyzed by TPO, attachment of one iodide to tyrosine within the Tg molecule yields MIT.
5b Attachment of two iodides to tyrosine yields DIT.
6a Coupling of one MIT and one DIT yields T3.
6b Coupling of two DITs yields T4.
7 On appropriate stimulation, the thyroid follicular cells engulf a portion of Tg-containing colloid by phagocytosis.
8 Lysosomes attack the engulfed vesicle and split the iodinated products from Tg.
9a T3 and T4 diffuse into the blood (secretion).
9b MIT and DIT are deiodinated, and the freed iodide is recycled for synthesizing more hormone.
Thyroid
follicle
Process forms MIT and DIT.
Coupling of MIT and DIT forms thyroid hormones.
MIT coupled to DIT produces T3
DIT coupled to DIT produces T4
Tyrosine-containing thyroglobulin is exported
from follicular cells into colloid by exocytosis.
Iodine from blood pumped into colloid.
Within colloid iodine attaches to tyrosine.
Fig. 19-2, p. 688

6. Thyrotropin-releasing
Stress
Cold in infants
Regulated negative-feedback between hypothalamic TRH, anterior pituitary TSH, and thyroid gland T3 and T4.
Main determinant of basal metabolic rate.
Influences synthesis and degradation of carbohydrate, fat, and protein.
Increases responsiveness to catecholamines.
Increases heart rate and force of contraction.
Essential for normal growth.
Plays crucial role in normal development of nervous system.
Hypothalamus
Thyrotropin-releasing
hormone (TRH)
Anterior pituitary
Thyroid-stimulating
hormone (TSH)
Figure 19.3: Regulation of thyroid hormone secretion.
Thyroid gland
Thyroid hormone
(T3 and T4)
Metabolic rate and heat production;
enhancement of growth and CNS development;
enhancement of sympathetic activity
Fig. 19-3, p. 689

7. Hypothyroidism Causes: Treatment:
primary due to failure of thyroid gland
secondary due to deficiency of TRH, TSH
inadequate dietary supply of iodine
Treatment:
taking replacement thyroid hormone
providing dietary iodine for deficiency
Symptoms:
reduced BMR, poor cold tolerance, excessive weight gain, fatigue, decreased cardiac output, slow reflexes and slow mental responsiveness
myxedema from accumulation of water-retaining carbohydrate molecules
in infants causes cretinism characterized by dwarfism and mental retardation

8. Hyperthyroidism Causes: Treatment:
Grave’s Disease when body produces thyroid-stimulating immunoglobulins (TSI)
secondary to excess TRH or TSH
Treatment:
removal of over-secreting thyroid lobes
administration of radioactive iodine
use of antithyroid drugs
Symptoms:
increased BMR, poor heat tolerance, excessive weight loss, skeletal muscle loss, increased cardiac output, excessive degree of mental alertness leading to agitation/anxiousness
Exophthalmos (bulging) eyes
Goiter: enlarged thyroid gland develops when the thyroid gland is overstimulated

9. Adrenal Glands Secretes hormones called “corticoids”
Located above each kidney
Composed of two endocrine organs:
adrenal cortex
outer portion
secretes steroid hormones
adrenal medulla
inner portion
secretes catecholamines Consists of three layers:
zona glomerulosa, outer layer
zona fasciculata, middle layer
zona reticularis, inner layer
Secretes hormones called “corticoids”
mineralocorticoids
glucocorticoids
sex hormones

10. (dehydro-epiandrosterone)
Capsule
Zona
glomerulosa
Zona
fasciculata
Cortex
Zona
reticularis
Adrenal
medulla
Adrenal
cortex
Medulla
Connective tissue
capsule
Adrenal
gland
Mineralocorticoids
(aldosterone)
Zona
glomerulosa
Zona
fasciculata
Figure 19.7: Anatomy of and hormonal secretion by the adrenal glands.
Glucocorticoids
(cortisol)
and
sex hormones
(dehydro-epiandrosterone)
Cortex
Zona
reticularis
Catecholamines
(epinephrine and
norepinephrine)
Medulla
(a) Location and gross structure of adrenal glands
(b) Layers of adrenal cortex
Fig. 19-7, p. 693

11. Dehydroepiandrosterone (adrenal cortex hormone)
Cholesterol
17-Hydroxypregnenolone
Pregnenolone
Dehydroepiandrosterone
(adrenal cortex hormone)
17-Hydroxyprogesterone
Progesterone
Androstenedione
Estrone
(female sex hormone)
11-Deoxycorticosterone
Deoxycortisol
Testosterone
Estradiol
Androgens
(male sex hormones)
Figure 19-8 Steroidogenic pathways for the major steroid hormones. All steroid hormones are produced through a series of enzymatic reactions that modify
cholesterol molecules, such as by varying the side groups attached to them. Each steroidogenic organ can produce only those steroid hormones for which it has a complete
set of the enzymes needed to appropriately modify cholesterol, after first converting it to pregnenolone. The active hormones produced in the steroidogenic pathways
are highlighted by screens. The intermediates that are not biologically active in humans are not screened.
Corticosterone
Cortisol
Estriol
Estrogens
(female sex hormones)
Aldosterone
Glucocorticoid
(adrenal cortex hormone)
Mineralocorticoid
adrenal cortex hormone)
Fig. 19-8, p. 694

12. Adrenal Cortex Glucocorticoids: Mineralocorticoids: Sex hormones:
produced primarily in zona fasciculata
major hormone is cortisol
plays role in nutrient metabolism
increase levels of blood glucose by gluconeogenesis
involved in stress resistance
exerts anti-inflammatory and immunosuppressive effects
Mineralocorticoids:
produced by zona glomerulosa
primarily aldosterone
increase Na+ reabsorption and K+ secretion
help maintain blood pressure homeostasis
mineralocorticoids are essential for life
Sex hormones:
produced in inner two layers
similar to testosterone
no effects in males
most important is dehydroepiandosterone (DHEA)
regulates sex drive and growth of axillary and pubertal hair in females

13. Stress
Diurnal rhythm
Hypothalamus
Corticotropin-releasing
hormone (CRH)
Anterior pituitary
Adrenocorticotropic
hormone (ACTH)
Adrenal cortex
Figure 19.9: Control of cortisol secretion.
Cortisol
Blood glucose
(by stimulating gluconeogenesis
and inhibiting glucose uptake)
Metabolic fuels
and building blocks
available to help
resist stress
Blood amino acids
(by stimulating protein degradation)
Blood fatty acids
(by stimulating lipolysis)
Fig. 19-9, p. 696

14. Cortisol Hyper/hyposecretion
Cushing’s syndrome
Causes:
overstimulation of adrenal cortex
adrenal tumors secrete excess cortisol
Signs and symptoms:
hyperglycemia and glucosuria (adrenal diabetes)
abnormal fat distributions “buffalo hump” and “moon face”
Primary adrenocortical insufficiency known as Addison’s disease:
all three layers under-produce hormones
changes in blood pressure, nutrient metabolism

15. Adrenal Medulla Contains modified sympathetic postganglionic neurons.
Primary stimulus for secretion is sympathetic nervous system.
Releases epinephrine and norepinephrine:
Epinephrine 80%
Norepinephrine 20% of secretion
Epinephrine:
reinforces sympathetic system in mounting general systemic “fight-or-flight” responses
maintenance of arterial blood pressure
increases blood glucose and blood fatty acids

16. Endocrine Control of Fuel Metabolism
all the chemical reactions that occur within the cells of the body
Intermediary metabolism or fuel metabolism
includes reactions involving degradation, synthesis, and transformation of proteins, carbohydrates, and fats

17. Tissues in Metabolism Liver: Adipose tissue: Muscle: Brain:
primary role in maintaining normal blood glucose levels
principal site for metabolic interconversions
Adipose tissue:
primary energy storage site
important in regulating blood fatty acid levels
Muscle:
primary site of amino acid storage
major energy user
Brain:
normally uses only glucose for energy
does not store glycogen
blood glucose levels must be maintained to supply energy source to brain

18. Dietary carbohydrate
Food intake
Dietary
triglyceride fat
Dietary protein
D I G E S T I O N
Absorbable units
Amino acids
Glucose
Fatty acids
Monoglycerides
A B S O R P T I O N
Storage, structural,
and functional
macromolecules
in cells
= Anabolism
= Catabolism
Metabolic
pool in body
Urea Urinary excretion (elimination from body)
Figure 19.14: Summary of the major pathways involving organic nutrient molecules.
Body proteins
(structural or
secretory products)
Amino
acids
Use as metabolic fuel
in cells:
Oxidation to
CO2+H2O+ATP (energy)
Glycogen storage
in liver and muscle
Glucose
Triglycerides
in adipose tissue
stores (fat)
Fatty acids
Expired
(elimination from body)
Fig , p. 705

19. Table 19-3 p704

20. Stressor is any stimulus that causes stress response.
Stress is generalized nonspecifc response of the body to any factor that overwhelms, or threatens to overwhelm, the body’s compensatory ability to maintain homeostasis.
Stressor is any stimulus that causes stress response.
All actions coordinated by the hypothalamus.
Hypothalamus
CRH
Posterior
Pituitary
Sympathetic
nervous system
Anterior
pituitary
Vasopressin
ACTH
Conserve salt and
H2O to expand the
plasma volume;
help sustain blood
pressure when
acute loss of plasma volume occurs Vasopressin and
angiotensin II
cause arteriolar
vasoconstriction
to increase blood
pressure
Adrenal medulla
Adrenal cortex
Epinephrine
Cortisol
Prepare body for
“fight or flight”
Mobilize energy
stores and metabolic
building blocks for use as needed
Figure Integration of the stress response by the hypothalamus.
Arteriolar
smooth muscle
Glucagon-secreting cells
Insulin-secreting cells
Endocrine
pancreas
Vasoconstriction
Blood flow
through kidneys
Glucagon
Insulin
Renin Angiotensin Aldosterone
Fig , p. 703

21. Table 19-2 p702

22. 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
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)
Hepatic glucose production:
––Through glycogenolysis
of stored glycogen
––Through gluconeogenesis
Figure Factors affecting blood glucose concentration.
KEY
= Factors subject to hormonal control to maintain blood glucose level
Fig , p. 710

23. Insulin and glucagon Insulin Anabolic hormone Glucagon
Lowers blood concentration of glucose, fatty acids, and amino acids by promoting cellular uptake.
Enhances their conversion into glycogen, triglycerides, and proteins.
Secretion is increased during absorptive state.
Primary stimulus for secretion is increase in blood glucose concentration.
Glucagon
Catabolic hormone
Secreted during postabsorptive state in response to a fall in blood glucose.
Mobilizes energy-rich molecules from their stores.
Increases blood glucose levels.
In general opposes the actions of insulin.

24. Sympathetic stimulation (and epinephrine) Islet  cells
Blood amino acid
concentration
Gastrointestinal
hormones (incretins)
Blood amino acid
concentration
Major control
Food intake
Parasympathetic
stimulation
Sympathetic stimulation
(and epinephrine)
Islet  cells
Figure Factors controlling insulin secretion.
Insulin secretion
Blood glucose
Blood fatty acids
Blood amino acids
Protein synthesis
Fuel storage
Fig , p. 713

25. Most common of all endocrine disorders.
Diabetes Mellitus
Most common of all endocrine disorders.
Results in elevated blood glucose levels.
Two major types:
type I diabetes characterized by lack of insulin secretion.
type II diabetes characterized by reduced sensitivity of insulin’s target cells.

26. Endocrine Control of Calcium Metabolism
Plasma Ca2+ must be closely regulated to prevent changes in neuromuscular excitability.
Role in other essential activities:
excitation-contraction coupling in cardiac and smooth muscle
stimulus-secretion coupling
maintenance of tight junctions
clotting of blood
Three hormones regulate plasma concentration of Ca2+ (and PO43-)
parathyroid hormone (PTH)
calcitonin
vitamin D

27. PTH/Vitamin D/Calcitonin
Secreted by parathyroid glands.
Primary regulator of Ca2+
Actions:
promotes Ca2+ movement from bone fluid into the plasma
enhances Ca2+ reabsorption by kidneys
facilitates activation of vitamin D
Vitamin D
Stimulates Ca2+ and PO43- absorption from intestine.
Can be synthesized from cholesterol derivative when exposed to sunlight.
Supplemented by dietary intake.
Must be activated first by liver and then by kidneys before it can affect the intestines.
Calcitonin
Produced by the C cells of the thyroid gland.
Secreted in response to an increase in plasma Ca2+
Lowers plasma Ca2+ by inhibiting activity of bone osteoclasts.
Calcitonin is unimportant except during the rare condition of hypercalcemia.

28. Plasma Ca2+ Plasma Ca2+ Parathyroid glands Thyroid C cells PTH
Figure Negative-feedback loops controlling parathyroid hormone
(PTH) and calcitonin secretion.
PTH
Calcitonin
Plasma Ca2+
Plasma Ca2+
Fig , p. 729

29. Figure 19-27 Activation of vitamin D.
Precursor in skin
(7-dehydrocholesterol)
Dietary vitamin D
Sunlight
Vitamin D3
Hydroxyl group (OH)
Liver enzymes
25-OH-vitamin D3
Figure Activation of vitamin D.
Hydroxyl group
PTH Plasma Ca2+
Kidney enzymes
Plasma PO43−
1,25-(OH)2-vitamin D3
(active vitamin D)
Promotes intestinal absorption of Ca2+ and PO43−
Fig , p. 730