Endocrine Function and Hormone Control

1
Endocrine Function and Hormone Control

• Pathophysiology
• N280
• Fall 2004

2
Endocrine System

• Various glands throughout the body
• Synthesize and release hormones (chemical
  messengers)
• Five functions
• 1. differentiation of the reproductive and CNS
  in the developing fetus
• 2. stimulation of sequential growth and
  development during childhood and adolescence

3
Endocrine System

• Five functions (continued)
• 3. coordination of the male and female
  reproductive systems, which makes sexual
  reproduction possible
• 4. maintenance of an optimal internal
  environment
• 5. initiation of corrective and adaptive
  responses when emergency demands occur
• Hormones are integrated with the nervous system
  to maintain communication

4
Principal Endocrine Glands

• Hypothalamus
• Pituitary
• Thyroid
• Adrenals
• Pancreas
• Ovaries/testes

5
Shared Characteristics of Hormones

• 1. Specific patterns and rates of secretion
• Diurnal patterns
• Pulsatile and cyclic patterns
• Circulating substrate dependent
• 2. Operate within feed systems
• Positive
• Negative
• 3. Affect only cells with specific receptors
  (target cells)
• Initiates specific function or activity
• 4. Liver metabolizes, kidneys excrete

6
Chemical Structure of Hormones

• Peptides
• Glycoproteins
• Polypeptides
• Amines
• Steroids
• Fatty acids

7
Polypeptide and Protein Hormones

• Most common type
• Made up of amino acids ranging from 3-200 amino
  acids long
• Polypeptides gt 100 amino acids are proteins
• Polypeptides lt 100 amino acids are peptides
• Stored in cytoplasma and bound to cell membrane
• Water soluble
• Generally circulate free (unbound)

8
Steroid Hormones

• Synthesized from cholesterol, not stored
• Lipid-soluble, diffuse across cell membrane into
  interstitial fluid then into blood

9
Amine Hormones

• Two groups of hormones derived from tyrosine
• Thyroid hormone stored in thyroid gland
• Adrenal medulla secretes epinephrine and
  norepinephrine

10
Regulation of Hormone Release

• Negative feedback
• Endocrine regulation (a hormone from one
  endocrine gland controlling another)
• Neural control

11
Feedback Systems

• Negative
• Most common
• The rising hormone level negates the initiating
  change that triggered the release of hormone
• Positive
• Rare
• Occurs when hormone secretion continues to
  trigger additional hormone

12
Negative Feedback System
13
Regulation of Hormone Release

• Endocrine regulation
• Regulation of hormone secretion by hormones
  themselves (through feedback loops)
• Neural regulation
• The release of a hormone or stimulus to produce
  hormone in response to activation of ANS
• Example epinephrine is released from the
  adrenal medulla as a response to stress

14
Hormone Transport

• Hormones are released into the circulatory system
  to be distributed throughout the body
• Protein (peptide) hormones are water soluble and
  generally circulate free (unbound)
• Insulin, growth hormone, prolactin, PTH
• Lipid-soluble hormones are transported bound to a
  carrier or transport protein
• Estrogen, cortisol, progestins, testosterone
• Only free hormones can signal a target cell

15
Mechanisms of Hormone Action

• Hormone receptors of target cell
• 1. recognize and bind specifically and with high
  affinity to their particular hormones
• 2. initiate a signal to appropriate
  intracellular effectors
• Target cells can up regulate or down regulate the
  number of receptors depending on the
  concentration of hormone

16
Target Cell Regulation
17
Mechanisms of Hormone Action

• Hormones affect target cells directly or
  permissively
• Direct effects are obvious changes in cell
  function that result from stimulation of specific
  hormone
• Permissive effects are less obvious
  hormone-induced changes that facilitate maximal
  response or functioning of a cell
• Example insulin has direct effect on skeletal
  muscle cells to increase glucose transport into
  cells it has a permissive effect on mammary
  cells to facilitate the response of these cells
  to the direct effects of prolactin

18
Hormone Receptors

• Located on plasma membrane or in the
  intracellular compartment of the target cell
• Water-soluble hormones cannot diffuse across the
  cell membrane (high molecular weight)
• Interact or bind with receptors in or on the cell
  membrane
• Fat-soluble steroid, vitamin D, retinoic acid,
  and thyroid hormones diffuse freely across cell
  membranes

19
First and Second Messengers

• First messenger is the hormone that is secreted
  into the blood stream and carries a message to
  the target cell. It interacts with the receptor
  on the cell membrane which initiates a signal
  that generates a
• Second messenger inside the cell to activate a
  response

20
Steroid (lipid-soluble) Hormone Receptors

• These are relatively small molecules and can
  cross the plasma membrane by simple diffusion
• Receptors for steroid hormones are in the cytosol
  and nucleus and direct gene expression

21
Structure and Function of the Endocrine Glands

• Hypothalamic-pituitary system
• Pituitary gland produces hormones that regulate
  several other endocrine glands
• Anterior and posterior lobes
• Located in the sella turcica (a saddle-shaped
  depression of the sphenoid bone at the base of
  the skull)
• Hypothalamus nerve endings innervate posterior
  pituitary

22
The Anterior Pituitary

• 75 total weight of pituitary gland, glandular
• Composed of three regions
• Pars distalis
• Pars tuberalis
• Pars intermedia (disappears in the adult)
• Composed of two main cell types
• Chromophobes (nonsecretory)
• Chromophils (secretory)

23
Anterior Pituitary

• Anterior pituitary hormones are regulated by
• 1. secretion of hypothalamic peptide hormones or
  releasing factors
• 2. feedback effects of the hormones secreted by
  target glands
• 3. direct effects of other mediating
  neurotransmitters

24
Anterior Pituitary
25
Hormones of the Anterior Pituitary and their
Functions

• Adrenocorticotrophic hormone (ACTH)
• Regulates growth and secretion of the adrenal
  gland, (cortisol and androgenic steroids)
• Melanocyte-stimulating hormone (MSH)
• Promotes secretion of melanin and lipotropin by
  anterior pituitary (makes skin darker)
• Somatotrophic hormones
• Growth hormone (GH) regulates metabolic processes
  related to growth and adaptation
• Prolactin milk production

26
Hormones of the Anterior Pituitary and their
functions

• Thyroid-stimulating hormone (TSH)
• Stimulates production and secretion of thyroid
  hormone
• Luteinizing hormone (LH)
• Ovulation, progesterone production
• Follicle-stimulating hormone (FSH)
• Follicle maturation, estrogen production (women)
• Spermatogenesis (men)

27
Hormones of the Anterior Pituitary and their
Functions

• Beta-lipotropin
• Fat breakdown and release of fatty acids
• Beta-endorphins
• Analgesia may regulate body temperature, food
  and water intake

28
Hypothalamic Hormones and their Functions

• Regulate synthesis and inhibit release of
  hormones of the anterior pituitary
• Thyrotropin-releasing hormone (TRH)
• Stimulates release of TSH, modulates prolactin
  secretion
• Gonadotropin-releasing hormone (GnRH)
• Stimulates relase of FSH and LH
• Somatostatin
• Inhibits release of GH, decreases gastric
  motility, intestinal secretion and secretion of
  TSH, parathyroid hormone, renin, glucagon, and
  insulin

29
Hypothalamic Hormones and their Functions

• Growth hormone-releasing factor (GRF)
• Stimulates release of GH
• Corticotropin-releasing hormone (CRH)
• Stimulates release of ACTH and beta-endorphin
• Substance P
• Inhibits synthesis and release of ACTH
• Stimulates secretion of GH, FSH, LH, and prolactin

30
Hypothalamic Hormones and their Functions

• Prolactin-inhibiting factor (PIF)
• Inhibits secretion of prolactin
• Prolactin-releasing hormone (PRH)
• Stimulates secretion of prolactin

31
The Posterior Pituitary

• The embryonic posterior pituitary is composed of
  three parts
• 1. the median eminence
• Contains biologically active hypothalamic-releasin
  g hormones, and neurotransmitters (dopamine,
  norepinephrine, serotonin, acetylcholine, and
  histamine
• 2. the pituitary stalk
• Connects the pituitary gland to the brain
• 3. the pars nervosa
• Secretes the hormones of the posterior pituitary

32
Posterior Pituitary Hormones

• Antidiuretic hormone (ADH)
• Vasopressin
• Oxytocin
• Both are synthesized in the hypothalamus and are
  stored in the posterior pituitary where they are
  released
• Release is regulated by cholinergic and
  adrenergic neurotransmitters
• Cholinergic stimulate while beta-adrenergic
  inhibit secretion of hormones

33
Antidiuretic Hormone (ADH)

• Controls plasma osmolality
• Secretion of ADH is regulated by osmoreceptors of
  the hypothalamus
• Factors that increase secretion of ADH include
• Loss of intravascular volume
• Barorecptors in left atrium, carotid, and the
  aortic arches
• An increase in plasma osmolity
• Stress, trauma, pain, exercise, nausea, nicotine,
  exposure to heat, and drugs (such as morphine)

34
Antidiuretic Hormone (ADH)

• Factors that decrease secretion of ADH
• Decreased plasma osmolality
• Increased intravascular volume
• Hypertension
• Alcohol ingestion
• ADH has no direct effect on electrolyte levels
• Inhibits urine production by causing the renal
  tubules to reabsorb water from the urine and
  return it to the circulating blood

35
Oxytocin

• Has antidiuretic effect similar to ADH
• In women
• Acts on the uterus to stimulate contractions
• Enhances effectiveness of contractions, promotes
  delivery of placenta, prevents excessive
  postpartum bleeding
• Is secreted in response to suckling to aid in
  milk ejection in lactating women (let-down
  reflex)
• In men
• May affect sperm motility

36
The Thyroid Gland

• A butterfly-shaped gland with 2 lobes located in
  the neck just below the larynx
• Consists of glandular tissue with follicles
  filled with thyroglobin (TG)
• Produces hormones that control rates of metabolic
  processes throughout the body
• Responsible for growth and development in children

37
Thyroid Hormones and their Functions

• Thyroid Hormone (TH)
• Secretion is initiated by release of TSH
• Affects most tissues
• Increases rate of protein, fat, and glucose
  metabolism
• Regulates body heat production
• Maintains growth hormone secretion, skeletal
  maturation
• Maintains cardiac rate, force, and output
• Maintains secretion of GI tract
• Affects respiratory rate

38
Thyroid Hormones and their Functions

• Thyroid Hormone (TH)
• Regulated thru a negative feedback loop
• Thyrotropin-releasing hormone (TRH) which is
  synthesized and stored in the hypothalamus is
  released into the hypothalamic-pituitary portal
  system
• TRH stimulates release of Thyroid-stimulating
  hormone (TSH) from the anterior pituitary
• 1. immediate release of stored thyroid hormone
  (TH)
• 2. increase in iodide uptake and oxidation
• 3. increase in thyroid hormone synthesis
• 4. increase in synthesis and secretion of
  prostaglandins by thyroid

39
Thyroid Hormones and their Function

• Calcitonin
• Secreted by C cells
• Lowers serum cholesterol levels
• Lowers serum phosphate levels
• May decrease calcium and phosphorus absorption in
  the GI tract

40
Parathyroid Glands

• 4-6 (2-3 pair)
• Produces parathyroid hormone (PTH)
• Regulates serum ionized calcium
• PTH secretion is affected by serum calcium levels
• Causes bone breakdown and resorption in bone
• In kidney causes increased reabsorption of
  calcium and inhibits reabsorption of phosphorus
  and bicarb

41
Pancreas

• Is considered an endocrine gland (producing
  hormones) and an exocrine gland (producing
  digestive enzymes)
• Regulates carbohydrate metabolism
• Houses the Islets of Langerhans
• alpha cells secrete glucagon
• beta cells secrete insulin and amylin
• delta cells secrete gastrin and somatostatin
• f cells secrete pancreatic polypeptide

42
Pancreatic Hormones and their Function

• Insulin
• Synthesized by beta cells
• Regulated by chemical, hormonal and neural
  control
• Stimulated by increased blood levels of glucose,
  amino acids and gastrointestinal hormones or
  parasympathetic stimulation of beta cells
• Secretion is diminished by low blood levels of
  glucose, high levels of insulin and sympathetic
  stimulation of alpha cells
• Promotes glucose uptake and synthesis of
  proteins, carbohydrates, lipids and nucleic acids
• Facilitates intracellular transport of potassium,
  phosphate and magnesium

43
Pancreatic Hormones and their Function

• Amylin
• Peptide hormone co-secreted with insulin
• Regulates blood glucose
• Delays nutrient uptake and suppresses glucagon
  secretion after meals
• Has satiety effect
• Glucagon
• Produced by alpha cells and cells lining GI tract
• Antagonistic to insulin
• Release stimulated by low glucose blood levels
  and sympathetic stimulation, inhibited by high
  glucose levels

44
Pancreatic Hormones and their Functions

• Somatostatin
• Essential in carbohydrate, fat and protein
  metabolism
• Involved in regulating alpha cell and beta cell
  function within the islets by inhibiting
  secretion of insulin, glucagon and pancreatic
  polypeptide
• Pancreatic polypeptide
• Secreted by F cells in response to hypoglycemia
  and protein rich meals
• Inhibits gallbladder contraction and exocrine
  pancreas secretion

45
Adrenal Glands

• Paired pyramid-shaped organs above kidneys
• Two portions
• Inner medulla is innervated by sympathetic and
  parasympathetic fibers
• Outer cortex consists of glandular tissue, 3
  zones
• 1. zona glomerulosa-outer layer, produces
  mineralocorticoid (aldosterone)
• 2. zona fasciculata-middle layer, secretes
  glucocorticoids cortisol, cortisone,
  corticosterone
• 3. zona reticularis-inner layer, secretes
  mineralocorticoids (aldosterone), adrenal
  androgens and estrogens and glucocorticoids

46
Adrenal Cortex Hormones and their Function

• Glucocorticoids
• Mineralocorticoids
• Adrenal androgens and estrogens
• Adrenal cortex must be stimulated by ACTH for
  cholesterol to be used in steroidogenesis

47
Adrenal Cortex Hormones and their Function

• Glucocorticoids
• Metabolic, inflammatory, anti inflammatory and
  growth-suppressing effects
• Influence levels of awareness and sleep patterns
• Direct effects on carbohydrate metabolism
• Promote glucogenesis in liver
• Inhibit bone formation and ADH secretion
• Stimulates gastric acid secretion
• Increase circulating erythrocytes and appetite
• Promotes fat deposition in face
• Suppress secretion and synthesis of ACTH

48
Adrenal Cortex Hormones and their Function

• Glucocorticoids
• Permissive effects
• Sensitizing arterioles to vasoconstrictive
  effects of norepinephrine
• Potentiate the effects of catecholamines, thyroid
  hormone, and growth hormone on adipose tissue
• May depress nerve cell function in the brain

49
Adrenal Cortex Hormones and their Function

• CORTISOL
• Needed to maintain life and protect body from
  stress
• Regulated by hypothalamus (CRH) and anterior
  pituitary gland (ACTH)

50
Glucocorticoid Synthesis
51
Adrenal Cortex Hormones and their Function

• Mineralocorticoids ALDOSTERONE
• Directly affect ion transport by epithelial cells
• Sodium retention, potassium and hydrogen loss
• Increases activity of sodium pump
• Regulated by renin-angiotensin system
• Activated by water depletion, increased potassium
  levels and decreased blood volume
• Enhancement of cardiac muscle contraction
• Stiffening of blood vessels (increases
  resistance)
• Decreased fibrinolysis

52
Aldosterone Secretion
53
Adrenal Cortex Hormones and their Function

• ADRENAL ESTROGENS ANDROGENS
• Secreted in minimal amounts
• Some conversion of ACTH to testosterone by
  peripheral tissues
• Adrenal androgens may also be converted to
  estrogens (this process is enhanced by aging,
  obesity, liver disease, and hyperthyroidism)
• ACTH is major regulator
• Biological effects are same as those produced by
  the gonads

54
Adrenal Medulla Hormones and their Function

• Catecholamines
• Epinephrine (adrenaline)
• Increases blood glucose levels
• Increases rate and force of cardiac contractions,
  constricts vessels of skin, mucous membranes and
  kidneys
• Dilates vessels in skeletal muscles, coronary
  arteries and pulmonary arteries
• Norepinephrine
• Fight or flight response
• Hyperglycemia
• Immune suppression
• Stress response

55
Gonads

• Testes and ovaries
• Regulate body growth and promote onset of puberty
• Men androgens (testosterone)
• Maintain reproductive function secondary sex
  characteristics
• Promote production of sperm
• Women estrogen and progesterone
• Maintain reproductive function secondary sex
  characteristics

56
Aging Effects

• General changes seen with aging include atrophy
  and weight loss with vascular changes
• Decrease in secretion and clearance of hormones
• Variable changes in receptor binding and
  intracellular responses