The Endocrine System I

1
The Endocrine System I

• Hormone classification
• Hormone activity and its mechanisms
• Hypothalamus and pituitary gland

2
Nervous system vs. endocrine system
3
The Endocrine System

• Hormones are secreted from the cells of endocrine
  glands into interstitial fluid and then diffuse
  into capillaries
• Hormones are carried by the blood throughout the
  body
• Most of the cells of the body are targets of
  hormones
• Hormones regulate growth, development, body
  defenses, water, electrolyte and nutrient balance
  in blood, energy and metabolism

4
The Endocrine System

• Endocrinology
• Major endocrine organs
• Hypothalamus a neuroendocrine organ
• Mixed endocrine and exocrine organs

5
Circulating and local hormones

• Circulating hormones enter the blood.
• Paracrine hormones act on neighboring cells.
• Autocrine hormones act on the secreting cell.

6
Hormone classes

• Steroid hormones are derived from cholesterol.
• Amino acids
• Amine hormonesepinephrine, norepinephrine,
  dopamine, serotonin, histamine.
• Peptide hormones (3-49AA)antidiuretic hormone,
  oxytocin
• protein hormones (50-200AA)human growth hormone,
  insulin, thyroid stimulating hormone (has a
  glycoprotein group)
• Eicosanoid hormones are
• Derived from arachidonic acidprostaglandins and
  leukotrienes.
• Released by almost all cells
• Primarily an autocrine or paracrine

7
Hormone transport in blood

• Water-soluble hormones circulate in a free form
• Lipid-soluble hormones are bound to transport
  proteins synthesized in the liver.
• They make lipid-soluble hormones temporarily
  soluble in the blood.
• They retard passage of the hormone molecules
  through the kidneys and into the urine.
• They make hormones more readily available from
  blood supplies.
• A small percentage of lipid-soluble are not bound
  and they pass through the capillaries and bind to
  receptors on cell membranes.

8
Hormonal actions

• Alter membrane permeability and/or membrane
  potential
• Stimulate synthesis of proteins
• Activate or deactivate enzymes
• Induce secretory activity
• Stimulate mitosis

9
Second messenger systems

• Hormones (1st messenger) bind to receptors on PM.
• Hormone-receptor complex activates a G-protein
• GDP is displaced by GTP which can either turn the
  target on (excite) or off (inhibit).

10
cAMP Signaling

• G-proteins

11
cAMP Signaling

• The G-protein activates adenylate cyclase.
• Adenylate cyclase converts ATP into cAMP.
• c-AMP activates protein kinase(s) that
  phosphorylates other proteins,
• Phosphorylation can either turn on proteins or
  inactivate them.
• Phosphorylated proteins produce physiological
  responses.
• Phosphodiesterase inactivates cAMP.

12
PIP-Calcium Signaling
13
PIP-Calcium Signaling

• GTP binds to phospholipase C
• Phospholipase C cleaves PIP into the second
  messengers DAG and IP3
• DAG activates protein kinase C
• IP3 increases cytosolic Ca2 levels
• Ca2 acts as second messenger
• Modifies activity of cellular proteins
• Acts on Ca2 channels
• Binds to the regulatory protein calmodulin

14
Lipid soluble hormones

• Hormone binds to receptor
• Hormone receptor-complex travels to nucleus
  binds to DNA
• Gene is turned on and produces mRNA

15
Mechanism of lipid-soluble hormones

• Receptors for lipid soluble hormones are inside
  the target cell.
• A free lipid-soluble hormoned diffuses through
  the capillaries and across PM into the cell
• Hormone binds to receptors within cytosol or
  nucleus.
• Activated receptor-hormone complex alters gene
  expression.
• Transcription of mRNA and translation into new
  proteins, often enzymes.
• New proteins alter cellular activity.

16
Target cell specificity

• A target cell must have receptors that bind a
  particular hormone for there to be an hormonal
  action.
• Hormones are a molecular trigger that depends on
• Blood levels of the hormone,
• The number of receptors on or in the target cell,
• The affinity and the strength of the bond between
  the receptor and the hormone.

17
Receptor sensitivity

• Receptors undergo dynamic changes in number.
• They are constantly being broken down and
  synthesized.
• They undergo desensitization which leads to
  down-regulation of the receptor.
• They undergo sensitization which leads to
  up-regulation of the receptor.

18
Duration of hormonal activity

• Hormones circulate in the blood, free or bound to
  a protein carrier.
• Concentration of a hormone depends on
• Its rate of release
• The speed at which it is inactivated and removed.
• The length of time it takes for the levels of a
  hormone to decrease by half is called the
  half-life.
• Hormones can also be released in an inactive
  form, which delays their effects.
• Duration of hormone action can vary between 10sec
  to several hours.

19
Hormonal interaction at target cells

• Permissivenessa hormone needs another hormone
  present in order to exert its effects.
• Synergismmore than one hormone produces the same
  effects, thus amplifying the signal.
• Antagonistsone hormone action opposes that of
  another.
• Antagonists can compete for same receptor.
• Act through different metabolic pathways.
• Can lead to down-regulation of the receptors of
  the antagonist

20
Control of hormonal release

• Synthesis and release are regulated by some type
  of negative feedback.
• Endocrine glands respond to 3 types of stimuli
• Humoral stimuliendocrine glands secrete hormones
  in response to chemical changes in the blood.
• Neural stimulinerve fibers stimulate release.
• Hormonal stimulihormones from other endocrine
  glands effect other glands downstream.
• Hormonal stimuli promote rhythmic hormonal
  release that leads to predictable increases and
  decreases in hormonal levels.
• Nervous system modulationthe ANS responds to
  particular environmental cues and changes. The
  drive towards homeostasis can lead to overiding
  normal endocrine control.

21
Endocrine gland stimuli
22
The Hypothalamus

• The major link between the nervous and endocrine
  system.
• Receives input from limbic system, cerebral
  cortex and thalamus .
• Receives sensory signals from internal organs and
  retina.
• Controls autonomic nervous system.
• Regulates body temperature, thirst, hunger,
  sexual behavior, fear and rage.
• Synthesizes at least 9 hormones.

23
(No Transcript)
24
The Pituitary Gland (Hypophysis)

• Anterior pituitarycomposed of glandular material
• Posterior pituitaryhormone storage area

25
Hormones of the anterior pituitary

• Pro-opiomelanocortin (POMC)
• Growth hormone (GH)
• Thyroid stimulating hormone (TSH)
• Adrenocortropic hormone (ACTH)
• Gonadotropins
• Follicle stimulating hormone (FSH)
• Luteinizing hormone (LH)
• Prolactin (PRL)

26
Tropic hormones

• Tropic hormones are those that stimulate the
  release of other hormones from endocrine glands.
• Tropic hormones all use cAMP as a second
  messenger
• Tropic hormones in the anterior pituitary
• TSH
• FSH
• LH
• ACTH

27
POMC

• A prohormone that is split enzymatically into
  active hormones.
• Adrenocorticotropic hormone
• Two opiatesenkephalin and a beta endorphin
• Melanocyte stimulating hormone (MSH)
• An NT involved in appetite
• Stimulate increase in melanin synthesis

28
Growthhormone
29
Growth hormones

• Secretion of GH is regulated by 2 hypothalamic
  hormones
• Growth hormone-releasing hormone
• Growth hormone-inhibiting hormonesomatostatin
• Produced by cells called somatotrophs
• Major targets are bones and skeletal muscles
• GH is an anabolic hormone that promotes protein
  synthesis and utilization of fat for energy.
• Growth promoting effects mediated via
  insulin-like growth factors (IGFs)
• GH is released on a daily rhythm and the amount
  peaks daily at night.

30
TSH, ACTH, Gonadotropins

• TRH stimulates release of TSH from thyrotrophs
• CRH stimulates release of ACTH from corticotrophs
  
• ACTH acts on adrenal gland
• CRH has a daily rhythm
• Glucocorticoids negatively regulate CRH
• GnRH stimulates release of gonadotropins
• FSH stimulates gamete production
• LH stimulates production of gonadal hormones

31
Prolactin

• Is regulated by the hypothalamus.
• Prolactin inhibiting hormone (dopamine) inhibits
  the relase of prolactin
• Prolactin releasing hormone
• Prolactin operates with other hormones to intiate
  and maintain milk secretion from the mammary
  glands.
• Permissive effects are required from estrogen,
  progesterone, glucocorticoids, human growth
  hormone, thyroxine, and insulin.
• Ejection of milk requires oxytocin.

32
Posterior pituitary

• Stores and releases two hormones
• Oxytocinacts on uterus, breasts and brain
• Antidiuretic hormone (vasopressin)decreases
  urine production

33
(No Transcript)