1. Chapter 18 Principles of Endocrinology; The Central Endocrine Glands

2. General Principles of Endocrinology Hypothalamus and pituitary
Outline
General Principles of Endocrinology
Free vs. bound, disorders, receptors
Hypothalamus and pituitary
Relationship
Anterior pituitary
Posterior pituitary
Endocrine control of growth
Pineal gland and circadian rhythms

3. General Principles of Endocrinology
Hormones are chemical messengers secreted by endocrine glands into the blood for transport.
Grouped into two categories:
hydrophilic hormones (peptides, catecholamines, indoleamines)
lipophilic hormones (steroid hormones and thyroid hormone)

4. Regulate organic metabolism. Regulate H2O and electrolyte balance.
Endocrine Functions
Regulate organic metabolism.
Regulate H2O and electrolyte balance.
Help body cope with stressful situations.
Promote sequential growth and development.
Control reproduction.
Regulate red blood cell production.
Control and integrate both circulation and the digestion and absorption of food.

5. Steroid Hormones Fig. 4-23, p. 116
Figure 4.23: 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. For example, the testes have the enzymes necessary to convert cholesterol into testosterone (male sex hormone), whereas the ovaries have the enzymes needed to yield progesterone and the various estrogens (female sex hormones).
Fig. 4-23, p. 116

6. Figure 4.22: Comparison of two steroid hormones, testosterone and estradiol.
Fig. 4-22, p. 115

7. Figure 4.26: Mechanism of action of lipophilic hormones via activation of genes.
(Source: Adapted with permission from George A. Hedge, Howard D. Colby, and Robert L. Goodman, Clinical Endocrine Physiology [Philadelphia: W. B. Saunders Company, 1987], Fig. 1-9, p. 20.)
Fig. 4-26, p. 122

8. Protein Hormones A chain and B-chain C- peptide NH2 NH2 COOH COOH S S
Fig 15-4, pg 456

9. Growth hormone Serotonin Insulin Tyrosine Monoiodotyrosine (MIT)
(c) 2003 Brooks/Cole - Thomson Learning
Tyrosine
Growth hormone
Monoiodotyrosine (MIT)
Diiodotyrosine (DIT)
T4 (thyroxine)
Serotonin
Insulin T3

10. `
Figure 4.24: Mechanism of action of hydrophilic hormones via activation of the cyclic AMP second-messenger system.
Fig. 4-24, p. 118

11. Figure 4.25: Activation of the calcium second-messenger system by an extracellular messenger.
Fig. 4-25, p. 119

12. Tropic Hormones Regulate hormone secretion by another endocrine gland
Stimulates and maintains their endocrine target tissues
Example
Thyroid-stimulating hormone (TSH) secreted from anterior pituitary stimulates thyroid hormone secretion by thyroid gland
Also maintains structural integrity of thyroid gland
hypothalamus
Releasing factors
pituitary
stimulating factors
Target cells/gland
Hormone regulation
Negative feedback

13. Fig. 4-21, p. 112 Figure 4.21: Types of intercellular communication.
Gap junctions and transient direct linkup of cells are both means of direct communication between cells. Paracrines, neurotransmitters, hormones, and neurohormones are all extracellular chemical messengers that accomplish indirect communication between cells. These chemical messengers differ in their source and the distance they travel to reach their target cells.
Fig. 4-21, p. 112

14. Figure 18-1 The endocrine system. Skin
Pineal
Hypothalamus
Pituitary
Thyroid
Parathyroid
Posterior view
Thymus
Heart
Liver
Stomach
Adrenal gland
KEY
Pancreas
Duodenum
Kidney
Adipose tissue
Figure The endocrine system.
Skin
Ovaries in female
Placenta in
pregnant female
KEY
Solely endocrine function
Testes in male
Mixed function
Fig. 18-1, p. 657

15. Regulate hormone secretion by another endocrine gland.
Tropic Hormones
Regulate hormone secretion by another endocrine gland.
Stimulate and maintain endocrine target tissues.
Example: thyroid-stimulating hormone (TSH)
secreted from anterior pituitary
stimulates thyroid hormone secretion by thyroid gland

16. Hormone Plasma Concentration
The rate of hormone secretion is the main regulator of effective plasma concentration.
The effective plasma concentration is also influenced by:
rate of removal by metabolic inactivation
rate of excretion
rate of peripheral activation
extent of binding to plasma proteins

17. Endocrine Dysfunction
Most commonly results from abnormal plasma concentrations of a hormone.
Caused by inappropriate rates of secretion.
hyposecretion too little secreted
hypersecretion too much secreted
Also occurs when there is decreased target-cell responsiveness to a hormone.

18. Table 18-1 p661

19. Target Cell Sensitivity
Target-cell sensitivity can be modified by:
down regulation; decrease in number of target-cell receptors
permissiveness; one hormone increases the effectiveness of another
synergism; combined effect of two hormones is greater than separate effects
antagonism; one hormone decreases the effectiveness of another

20. Pituitary Gland Known as hypophysis.
Stalk connects pituitary to hypothalamus.
Consists of two distinct lobes:
posterior pituitary (neurohypophysis) composed of nervous tissue
anterior pituitary (adenohypophysis) consists of glandular epithelial tissue
Release of hormones from both anterior and posterior pituitary is controlled by hypothalamus.

21. Figure 18-2 Diurnal rhythm of cortisol secretion.
Fig. 18-2, p. 660

22. Figure 4.26: Mechanism of action of lipophilic hormones via activation of genes.
(Source: Adapted with permission from George A. Hedge, Howard D. Colby, and Robert L. Goodman, Clinical Endocrine Physiology [Philadelphia: W. B. Saunders Company, 1987], Fig. 1-9, p. 20.)
Fig. 4-26, p. 122

23. Protein Hormones A chain and B-chain C- peptide NH2 NH2 COOH COOH S S
Fig 15-4, pg 456

24. Growth hormone Serotonin Insulin Tyrosine Monoiodotyrosine (MIT)
(c) 2003 Brooks/Cole - Thomson Learning
Tyrosine
Growth hormone
Monoiodotyrosine (MIT)
Diiodotyrosine (DIT)
T4 (thyroxine)
Serotonin
Insulin T3

25. `
Figure 4.24: Mechanism of action of hydrophilic hormones via activation of the cyclic AMP second-messenger system.
Fig. 4-24, p. 118

26. Figure 4.25: Activation of the calcium second-messenger system by an extracellular messenger.
Fig. 4-25, p. 119

27. Tropic Hormones Regulate hormone secretion by another endocrine gland
Stimulates and maintains their endocrine target tissues
Example
Thyroid-stimulating hormone (TSH) secreted from anterior pituitary stimulates thyroid hormone secretion by thyroid gland
Also maintains structural integrity of thyroid gland
hypothalamus
Releasing factors
pituitary
stimulating factors
Target cells/gland
Hormone regulation
Negative feedback

28. Table 18-2a, p. 659

29. Table 18-2c, p. 660

30. Table 18-2d, p. 661

31. Neural extension of the hypothalamus.
Posterior Pituitary
Neural extension of the hypothalamus.
Two small peptide hormones made in hypothalamus and stored in posterior pituitary:
vasopressin conserves water during urine formation
oxytocin stimulates uterine contraction during childbirth and milk ejection during breast-feeding

32. Figure 18-3 Anatomy of the pituitary gland.
Hypothalamus
Bone
Anterior
lobe of
pituitary
Figure 18-3 Anatomy of the pituitary gland.
Posterior
lobe of
pituitary
(a) Relation of pituitary gland to hypothalamus
and rest of brain
Fig. 18-3a, p. 662

33. Figure 18-3 Anatomy of the pituitary gland.
Hypothalamus
Optic
chiasm
Connecting stalk
Figure 18-3 Anatomy of the pituitary gland.
Posterior
pituitary
Anterior
pituitary
b) Enlargement of pituitary gland and its
connection to hypothalamus
Fig. 18-3b, p. 662

34. Anterior Pituitary
The anterior pituitary releases its hormones into the blood based on releasing and inhibiting hormones from the hypothalamus.
The hypothalamus is influenced by a variety of controlling inputs.
Most anterior pituitary hormones are tropic.

35. Neurosecretory neurons
in hypothalamus (secrete releasing and inhibiting hormones into portal system)
Hypothalamus
Releasing
and inhibiting
hormones 1
Capillaries in
hypothalamus 1
Systemic
arterial
blood in 2
Endocrine cells of
anterior pituitary
(secrete anterior
pituitary hormones
into systemic blood)
Hypothalamic-
hypophyseal
portal system 3
Figure Vascular link between the hypothalamus and anterior pituitary.
1) Hypophysiotropic hormones (releasing hormones and inhibiting hormones) produced by neurosecretory neurons in the hypothalamus enter the hypothalamic capillaries.
2) These hypothalamic capillaries rejoin to form the hypothalamic-hypophyseal portal system, a vascular link to the anterior pituitary.
3) The portal system branches into the capillaries of the anterior pituitary.
4) The hypophysiotropic hormones, which leave the blood across the anterior pituitary capillaries, control the release of anterior pituitary hormones.
5) When stimulated by the appropriate hypothalamic releasing hormone, the anterior pituitary secretes a given hormone into these capillaries.
6) The anterior pituitary capillaries rejoin to form a vein, through which the anterior pituitary hormones leave for ultimate distribution throughout the body by the systemic circulation.
Posterior
pituitary
Capillaries in
anterior pituitary 4 5
Systemic
venous
blood out
Anterior
pituitary 6
KEY
= Hypophysiotropic hormones = Anterior pituitary hormone
Fig. 18-7, p. 671

36. Anterior Pituitary
The anterior pituitary secretes six different peptide hormones that it produces itself.
Five are tropic:
Thyroid-stimulating hormone (TSH) stimulates secretion of thyroid hormone.
Adrenocorticotropic hormone (ACTH) stimulates secretion of cortisol by the adrenal cortex.

37. Anterior Pituitary Non-tropic Follicle-stimulating hormone (FSH) and
Luteinizing hormone (LH) stimulate production of gametes and secretion of sex hormones.
Growth hormone (GH) stimulates growth indirectly by stimulating liver secretion of IGF-I, which in turn promotes growth. Also exerts metabolic effects.
Non-tropic
Prolactin (PRL) stimulates milk secretion.

38. Hypothalamus Anterior pituitary Posterior pituitary
TSH
ACTH
Prolactin
Thyroid
gland
Adrenal
cortex
Mammary
glands
Thyroid hormone
(T3 and T4)
Cortisol
Breast growth and milk secretion
Increased
metabolic rate
Metabolic actions;
stress response
Figure Functions of the anterior pituitary hormones.
Five different endocrine cell types produce the six anterior pituitary hormones—TSH, ACTH, growth hormone, LH and FSH (produced by the same cell type), and prolactin—which exert a wide range of effects throughout the body.
Growth hormone
Liver
Adipose tissue,
muscle, liver LH
FSH
IGF-I
Gonads
(ovaries in
females)
(testes
in males)
Bone
Soft tissues
Sex hormone secretion
(estrogen and
progesterone in females,
testosterone in males)
Gamete production
(ova in females,
sperm in males)
Metabolic
actions
Growth
Fig. 18-5, p. 667

39. ANIMATION: Anterior Pituitary Function

40. Negative Feedback
Both hypothalamus and anterior pituitary are inhibited by negative-feedback in the hypothalamus–anterior pituitary–target-gland axis.
This negative feedback is accomplished by the target-gland hormone directly inhibiting the release of pituitary and hypothalamic hormones.

41. Neural
input
Hormonal
input
Stress
Hypothalamic
neurosecretory neuron
Hypothalamus
(secretes)
Corticotropin-releasing
hormone
Hormone 1
(Special short portal system)
(Special short portal system)
Anterior pituitary
Anterior pituitary
Negative
feedback
(secretes)
Adrenocorticotropic
hormone
(ACTH; corticotropin)
Hormone 2
(Systemic circulation)
(Systemic circulation)
Target endocrine gland
Adrenal cortex
Figure Hierarchic chain of command and negative feedback in endocrine control.
The general pathway involved in the hierarchic chain of command in the hypothalamus–anterior pituitary–peripheral target endocrine-gland axis is depicted on the left. The pathway on the right leading to cortisol secretion provides a specific example of this endocrine chain of command. The hormone ultimately secreted by the target endocrine gland, such as cortisol, acts in negative-feedback fashion to reduce secretion of the regulatory hormones higher in the chain of command.
(secretes)
Hormone 3
Cortisol
General circulation)
(General circulation)
Target cells
Most cells
Metabolic changes that help resist stress
Physiologic effect
Fig. 18-6, p. 670

42. Table 18-4 p669

43. Endocrine Control of Growth
Growth depends on growth hormone and other growth-influencing hormones.
Genetics, diet, and freedom from chronic disease or stress also play a role.
Major growth spurts occur the first few years after birth and during puberty.
GH is essential for growth, but also directly exerts metabolic effects not related to growth.

44. GH Actions
The GH–IGF-I pathway acts on soft tissues and bone to bring about growth.
Stimulates protein synthesis, cell division, and the lengthening and thickening of bones.
GH also directly exerts metabolic effects unrelated to growth.
GH increases fatty acid and blood glucose levels.
Glucose sparing saves glucose for brain.

45. GH Secretion
GH secretion by the anterior pituitary is regulated by two hypothalamic hormones:
growth hormone–releasing hormone (GHRH)
growth hormone–inhibiting hormone (somatostatin)
GH secretion displays diurnal rhythm, peaking one hour after deep sleep.

46. The world's tallest man (7.9 feet) and smallest man (2.4 feet)

47. Figure 18-10 Control of growth hormone secretion.
Exercise, stress,
blood glucose
Blood amino acids,
Blood fatty acids
Major
inputs
Minor
inputs
Diurnal rhythm
Ghrelin
Hypothalamus
Somatostatin (growth
hormone–inhibiting
hormone; GHIH)
Growth hormone–
releasing hormone
(GHRH)
Anterior pituitary somatotrope
Growth hormone
Figure Control of growth hormone secretion.
*These factors all increase growth hormone secretion, but it is unclear whether
they do so by stimulating GHRH or inhibiting GHIH somatostatin, or both.
Liver
Metabolic actions
unrelated to growth
fat breakdown
(blood fatty acids)
IGF-I
glucose uptake by muscles
(blood glucose)
glucose output by liver
(blood glucose)
Growth-promoting
actions cell division
protein synthesis
( blood amino acids)
bone growth
Fig , p. 676

48. Suprachiasmatic Nucleus
The suprachiasmatic nucleus (SCN) is the body’s biological clock.
Cyclic variations in the concentration of clock proteins in the SCN bring about cyclic changes in neural discharge from this area.
Each cycle takes about a day and drives the body’s circadian (daily) rhythms

49. Pineal Gland-Melatonin
Pineal gland’s secretion of melatonin rhythmically fluctuates with the light–dark cycle
Decreases in light and increases in dark.
Melatonin resets the body’s natural circadian rhythms to match external cues like the light–dark cycle.

50. Pathway to
visual cortex
Rods and
cones
Light
Dark
Vision
Melanopsin-containing
retina ganglion cells
Suprachiasmatic nucleus
(master biological clock)
Pineal gland
Cycle
takes
about
a day
Degradation of
clock proteins
Synthesis of
clock proteins
Melatonin
in the light
Melatonin
in the dark
Figure Synchronization and entrainment of circadian rhythms.
Cyclic changes
in clock proteins
Cyclic changes
in melatonin
Synchronizes
circadian rhythms
in effector organs
throughout body
Resets circadian
rhythms to match
light–dark cycle
Fig , p. 682

51. Food intake Dietary protein D I G E S T I O N Absorbable units Glucose
carbohydrate
Dietary triglyceride
fat
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
Metabolic pool
in body
Body proteins
(structural or
secretory
products)
Amino
acids
Urea Urinary excretion
(elimination from body)
Oxidation to
CO2 + H2O + ATP (energy)
Expired
(elimination from body)
Storage, structural, and
functional
macromolecules in cells
Glycogen storage
in liver and
muscle
Glucose
Triglycerides
in adipose tissue
stores (fat)
Fatty
acids
Use as metabolic fuel
in cells
Fig , p. 702