BL3 Hormonal Regulation: Biochemical Aspects

• Adrenal Hormones

  Produce catecholamines and glucocorticoids
• Cortisol

  Lowers glucose level by degrading protein and fat synthesis
• Epinephrine secretion


  Signaled by the neural response to stress
• Cortisol


  Induces phenylethanolamine N-methyltransferase (PNMT), a key enzyme catalyzing the conversion of norepinephrine to epinephrine
• Epinephrine synthesis, storage, and release

  Regulated by neuronal controls and glucocorticoid hormones
• Acetylcholine release by neuron

  Increases availability of intracellular calcium ion, which stimulates exocytosis and release of material stored in chromaffin granules
• Renin-angiotensin system

  Generates signal when blood [Na+] and blood pressure (blood volume) need to be increased
• Angiotensinogen cleavage by renin

  Produces angiotensin I
• Angiotensin I conversion

  Produces angiotensin II by the action of converting enzyme
• Angiotensin II conversion

  Produces angiotensin III by an aminopeptidase
• Angiotensin II and III binding to receptor


  Activates phosphatidylinositol cycle to generate IP3 and DAG
• IP3 stimulation

  Releases calcium ions from intracellular storage vesicles
• Angiotensin-receptor complex activity

  Stimulates Ca2+ channel activity
• Increased cytoplasmic Ca2+

  Stimulates aldosterone secretion and protein kinase C activity
• Increased protein kinase C activity

  Leads to protein phosphorylations that stimulate aldosterone synthesis
• Aldosterone entry into distal kidney cell

  Binds to receptor and stimulates expression of proteins that increase Na+ transport from glomerular filtrate to blood
• Atrial natriuretic factor (ANF) binding to receptor

  Activates guanylate cyclase, increasing cGMP
• Increased cGMP

  Antagonizes the synthesis and secretion of aldosterone as well as the formation of cAMP by adenylate cyclase
• ACTH control of cortisol

  Probably controls cortisol by controlling the movement of calcium into the cortisol-secreting target cells
• ACTH control

  Controlled by the hypothalamic peptide corticotropin-releasing hormone (CRH), which is under nervous control
• IL-1 secretion by activated macrophages

  Synergistically with CRH increases ACTH
• 1. cell secretion of glucosteroid response modifying factor (GRMF) and IL-1

  Increase the amount of cortisol required to inhibit almost all the immune cells
• Corticosterone


  Glucocorticoid produced by adrenal cortex, precursor to aldosterone
• Cortisol


  Primary glucocorticoid action
• Osmoreceptor cells in hypothalamus

  Monitor the osmolarity of blood
• Increased blood osmolarity


  Triggers more ADH release into bloodstream
• ADH reaching kidney

  Increases permeability of distal tubules and collecting ducts to water
• Increased water reabsorption

  Reduces urine volume and prevents further increase of blood osmolarity
• Subsiding blood osmolarity

  Reduces activity of osmoreceptor cells, less ADH is secreted
• Decreased ADH secretion

  Decreases permeability of distal tubules and collecting ducts, reducing water reabsorption and increasing dilute urine discharge
• GnRH release from hypothalamus

  Enters portal system and binds to receptor, causing release of FSH and LH from anterior pituitary
• FSH binding to ovarian follicle


  Stimulates synthesis and secretion of estradiol and maturation of follicle and ovum
• Inhibin synthesis

  Negative feedback regulator of FSH production
• LH binding to corpus luteum


  Stimulates synthesis of progesterone
• Absence of fertilization

  Corpus luteum involutes, progesterone and estradiol levels fall, menstruation occurs
• Fall in blood steroid levels

  Releases negative feedback inhibition on gonadotropes and hypothalamus, cycle starts again
• What is down regulation?

  When a hormone is secreted in excess, the number of receptors of that hormone decreases due to binding of hormone with receptors.
• What is upregulation?

  during the deficiency of the hormone, the number of receptor increases
• What is internalization?

  hormone in the form of hormone-receptor complex enters the target cell by means of endocytosis and executes the actions
• Hormone does not act on the target cell directly. It combines with receptor to form hormone-receptor complex. This complex executes the hormonal action by this mechanism:

  1. by altering permeability of cell membrane
  2. by activating intracellular enzyme
  3. by acting on genes