A. Production of Thyroid Hormone (aka Thyroxine or TH) -- see handout 22A or Sadava 41.9 (8th ed).

1. Biochemistry: Structure of TH -- How modification and rearrangement of tyrosines in thyroglobulin (TG) leads to TH.

2 Cell Biology: How is thyroxine made & stored?  How (& where) TG is made & TH released from it. 

• TH made in follicle of thyroid gland

• protein (TG) made on RER → Golgi → vesicles

• exocytosis of vesicles releases TG into lumen

• I- taken up into gland; I added to tyrosines of TG in lumen; one modified tyrosine added to OH of another. 

• Modified TG stored in lumen of gland = reservoir of TH

• TG taken up by cell from gland by RME. Result is degradation of TG in lysosomes → releases T4 or T3 (= TH)

• TH  diffuses out of cell across membrane. Acts like a steroid. (For structures see handout or texts.)

• TSH stimulates virtually all of these steps.

3. How does thyroxine travel through the blood? All lipid soluble hormones are attached to plasma proteins, either to general proteins or specific binding proteins for that hormone. T4 and T3 are transported by thyroxine-binding globulin, which is specific for thyroxine. Note: thyroglobulin is not the same as thyroxine-binding globulin. (Globulin just means globular, soluble protein.)

4. Newspaper article on role of Iodine and TH in development: In Raising the World’s I.Q., the Secret’s in the Salt This article is part of a series from the NY Times (2006). Articles in this series examine diseases that hover on the brink of eradication, and the daunting obstacles that doctors and scientists face to finish the job.

    B. Examples of how hormones and nerves co-operate to run a circuit. See handout 23A.

1. Lactation

a. Overall Loop: Suckling by baby → milk ejection ("letdown) → more suckling →  more milk ejection etc. Loop continues until baby stops nursing.

b. Signaling Pathway: Suckling by baby stimulates nerve endings in nipple → nerve signal to HT → release of oxytocin and prolactin as follows:

(1). Oxytocin: HT → release of oxytocin from neuron endings post. pit. → contraction of myoepithelial cells (similar to smooth muscle)  surrounding alveolus (milk producing section of mammary gland) → milk ejection from lumen of alveolus → more suckling → etc.

(2). Prolactin: HT  → PIH (= DA) down and PRH (?) up in portal vessel  → AP releases prolactin (PL) → stimulates inner layer of cells surrounding lumen of alveolus →  promotes milk production and secretion of milk into lumen of gland.

Question to think about: what does the circuit look like here? What's the IC? The effector? Etc.

2. Stress response   (Handout 23B.)

a. Phase one -- Nerve (Sympathetic) activity stimulates target organs (that are not glands) → Direct response of heart, liver, lungs, etc.

b. Phase two -- Nerve (Sympathetic activity) → activation of glands

(1). Stimulate pancreas → glucagon released stimulated; insulin release inhibited → secretion of glucagon → additional stimulation of some target organs

(2). Stimulate adrenal medulla → release of epinephrine → stimulation of same targets as sympathetic nerve activity & some additional targets -- hormones can reach where nerves can't go.

c. Phase three -- stimulate HT/AP axis to produce cortisol

 HT in brain → releases CRH → AP → releases ACTH → adrenal cortex → produces cortisol → target organs → stimulation of breakdown of fats & protein for energy (sparing glucose for brain); inhibition of immune system.

    A. Overall Function -- what does the kidney do?

1. Function: Controls water loss and determines what other specific components (including protons & other ions) will be excreted (lost in urine) and what will be retained.

2. What processes occur in kidney?

• Filtration

• tubular secretion  (addition of substances to the filtrate)

• tubular reabsorption (removal of substances from filtrate)

• control of volume.

We will do structure first (23C or Sadava fig. 51.7) & then how these processes occur (23D).

    B. Overall structure -- see handout 23C or Sadava fig. 51.9

1. Kidney has medulla (inner part) and cortex (outer)

2. Functional unit = nephron (Sadava 51.7 )

3. Visible unit (in medulla) = Renal Pyramid = bottoms of many nephrons

4. Tops of nephrons in cortex

    C. Structure of Nephron -- see handouts or Sadava fig. 51.7  & 51.9 . For EM pictures see Sadava 51.8. (We'll do the parts as we need them, but all are summarized here.)

Artery (from heart) → afferent arteriole → glomerular capillaries → efferent arteriole → peritubular capillaries → venule → vein (back to heart)

    D. Basic Processes

1. The 4 Basic Processes

a. Filtration:

(1). Occurs in glomerulus

(2). About 20% of blood liquid (plasma) enters Bowman's capsule = filtrate

(3). Filtrate contains no large proteins or cells

b. Tubular (selective) secretion: Material is added to the filtrate. Therefore filtrate carries high concentrations of certain dissolved materials (secreted by cells lining the lumen) -- removes waste, toxins from circulation.

Note: Secretion is NOT the same as excretion. Secretion = extruded by the cells into extracellular space (into filtrate, lumen, etc.).  Excretion = carried out of body in urine or feces.

c. Tubular (selective) reabsorption:  Material is removed from the filtrate. Therefore filtrate does NOT carry certain materials (which are selectively reabsorbed) -- conserves valuable materials; returns them to circulation.

d.  Volume: Water loss is adjusted later using ADH. Therefore urine can be more (or less) concentrated than the plasma -- can vary concentration and/or volume to suit need. Water loss/conservation controls volume of body fluids -- plasma, extra cellular fluid, etc. (& blood pressure)  

2. How does tubular secretion/reabsorption occur? Structure of cells lining tubules  -- see handout  23D or Sadava fig. 51.12 (for a different example).

a. Tubules lined by layer of polarized epithelial cells (similar to those lining intestine)

b. Materials must cross epithelial cells to enter or exit lumen of tubules.

c. Interstitial fluid separates epithelial cells and capillaries.

d. Epithelial cells have different proteins/channels/transporters on their two surfaces -- the apical or luminal surface (facing lumen) and basolateral surface (facing interstitial fluid and capillaries).

    D. Function of Nephron -- Let's follow some liquid through.

a. Luminal cell membranes in descending loop and lower part of ascending loop are permeable to water.

b. Luminal cell membranes in rest of ascending are impermeable to water and pump NaCl from lumen to interstitial fluid. (See 23D.)

c. NaCl pumped out from ascending loop accumulates in medulla, forming a gradient of increasing osmolarity (outside the tubule) as reach bottom of loop = core of medulla.

d. Filtrate from proximal tubule loses water as it descends into medulla → NaCl stays in tubule → high concentration NaCl in tubule→ to be removed in ascending.

e. If NaCl diffuses into descending loop, it is carried around and pumped out in ascending = escalator effect.

f. Why called countercurrent? Because flow in two sides of loop is in opposite directions  physically and with respect to osmolarity. First leg (descending) of loop removes water → higher osmolarity in filtrate; second leg (ascending) removes salt → lower osmolarity in filtrate.