C2006/F2402 '05 OUTLINE OF LECTURE #15
(c) 2005 Dr. Deborah Mowshowitz, Columbia University, New York, NY. Last update 03/24/2005 03:17 PM .
Handouts: Need 14B (Hormones Overall), 15A (Thyroid, catecholamines),15B (glands, organs) & (Homeostasis)
I. Overview of Major Glands & Hormones (handout 14B), cont. Review of last time; roles of adrenal & pancreas.
II. Details of HT/Ant. Pit. Axis
A. Hypothalamic Hormones
1. Inputs: Neuroendocrine cells in HT produce hormones -- in response to multiple inputs -- neuronal, hormonal, & local (detected by sensors for variables such as temperature, osmolarity, etc.).
2. Outputs: Neuroendocrine cells in HT are two kinds:
a. Some have bodies in HT and axons/terminals in posterior pituitary
(1). Release hormones (neuroendocrines) from endings (terminals) in post. pit --> blood supply.
(2). Hormones are peptides. Made in cell body, packaged in vesicles, vesicles travel down MT's to end of neurons, hormones released by exocytosis.
(3). Hormones = ADH (vasopressin) and oxytocin. Peptides are very similar in structure (homologous = share common evolutionary origin) but bind to different (G protein linked) receptors --> dif. effects. (See last lecture for details of effects.)
b. Some cells in HT release hormones from HT itself.
(1). Release hormones into portal vessel (connects two capillary beds) that goes direct to anterior pituitary. See Purves 42.7 (41.7) and handout 14B.
(2). Hormones released by HT affect production/release of other hormones by ant. pit.
(3). Affect on release can be stimulatory (RH's such as ACTH-releasing hormone) or inhibitory (IH's such as prolactin release-inhibiting hormone = PIH) For a complete list see Purves table 42.2 (41.2).
(4). All HT hormones (except PIH) are peptides/proteins.
(5). PIH (prolactin inhibiting hormone) = dopamine = modified amino acid.
c. Additional info on dopamine (DA) & related compounds = catecholamines
(1). Structures: See handout 15A for structures of catecholamines = epinephrine (aka adrenaline), norepinephrine (aka noradrenaline), and dopamine. These are all modified amino acids derived from tyrosine. All water soluble. (Note thyroxine is also derived from tyrosine but is not a catecholamine; it is lipid soluble -- see below.)
(2). Receptors: There are multiple receptors for all of the catecholamines. Receptors are classified by their ligands and response to drugs.
(a). Dopamine has its own receptors, separate from the adrenergic receptors.
(b). FYI: All adrenergic receptors bind to both epi and norepi. Some receptor types bind better to (have higher affinity for) one, some to the other, some equally well to both. Epinephrine acts mostly through beta adrenergic receptors; norepinephrine mostly through alpha adrenergic receptors.
(3). Mechanism of action: All receptors for all catecholamines are G protein linked; effects of hormones on any particular cell type depend on (i) what receptors are present, (ii) what G protein each receptor activates. Each G protein does one (or more) of the following: activate adenyl cyclase; inhibit adenyl cyclase; activate phospholipase C. See Lecture 13 & exam #2 for examples of different responses to epi due to diff. receptors.
B. Tropic Hormones of Anterior Pituitary (for names of hormones and target cells see handout 14B)
1. Made by ant. pit and influence other endocrine glands
2. Release controlled by hormones from HT
3. Effect on target tissue
a. Effect: Usually cause release of another hormone
b. What is released? Hormones released by targets are steroids or act like them (thyroxine)
c. Mechanism: All tropic hormones work through G linked receptors and cAMP.
4. Three major tropic hormone types -- each type named after its target -- see handout 14B & table below.
See problem 7-4. (Skip 5 for now.)
C. Other Hormones of ant. pit.
1. GH and prolactin -- "pseudo tropic" hormones→ secretion → outside
a. Structure & mechanism: Similar in structure to each other (homologous) and use a special type of TK receptor
b. What is released? Stimulate production of secretions, but not from endocrine glands.
(1). GH stimulates liver (& possibly other tissues) to produce insulin-like growth factors (ILGF 1 & 2); ILGF's from liver released into blood (act as endocrines); ILGF's from other tissues act as paracrines. (GH has other effects as well.)
(2). Prolactin stimulates mammary (exocrine) gland to produce milk. (Need oxytocin to eject the milk.)
(3). What's the difference between endocrine & exocrine glands? See handout 15B.
(a). Exocrine Gland
When gland forms, epithelial layer leaves duct to outside.
Secretion from gland flows into duct → outside or lumen.
(i) sweat, mammary & tear glands
(ii) stomach glands → secretion → lumen.
(b). Endocrine Gland
When gland forms, epithelial layer pinches off leaving no duct
Secretion (hormone) from gland enters blood.
Example: gonads, pancreas, adrenal.
Try problems 7-1 & 7-13.
2. MSH etc.
a. Common source: All come from cleavage of single peptide precursor (pro-opio-melanocortin or pomC) that is cut up to give ACTH and MSH etc.
b. Alternative ways of cleavage: Same precursor can be cut up different ways in different tissues and/or species. Note: this is alternative processing of a protein, not an RNA.
c. Function: Function of these hormones relatively obscure.
3. Summary of Tropic & "Pseudo-Tropic" Hormones of Ant. Pit
Tropic (or Pseudo-Tropic) Hormone(s)
Hormones/Secretions Made by Target Organ
ACTH (adrenal cortex tropic hormone) or adrenocorticotropin
Glucocorticoids, Mineralocorticoids & sex steroids*
Gonadotropins -- LH and FSH
Estrogens, androgens & progesterone*
TSH (thyroid stimulating hormone) or Thyrotropin
GH (Growth Hormone) = somatotropin
Liver (& others)
Insulin-Like Growth Factors
* All lipid soluble hormones travel through the blood attached to plasma proteins.
Try Problem 7-2 & 7-4 if not yet done, but skip 5 (of 7-4) for now.
D. HT/Anterior Pituitary Axis -- Set up & Regulation of overall circuit (HT → Ant. Pit. → target)
1. General case: See Purves 42.8 (41.8)
a. The cascade:
HT → releasing hormone → AP → tropic hormone → TARGET GLAND → hormone → TARGET TISSUE → action.
b. Regulation: Hormone (thyroxine, sex steroids, etc.) has negative feedback effect on HT and AP. Why inhibit both?
(1). Feedback inhibits HT -- alters production of releasing/inhibiting hormones (changing signal to AP)
(2). Feedback inhibits AP response to signal from HT (by down regulating receptors); may also directly inhibit synthesis of tropic hormone.
(3). Both neg. feedback effects lead to inhibition of release of tropic hormones from AP
2. Specific case: thyroxine production (See handout 15A; Purves fig. 42.8 (41.9)
a. The cascade:
HT → TRH → AP → TSH → TARGET GLAND → TH → TARGET TISSUE → increase in BMR, etc.
(1). Negative Feedback: TH inhibits production of both TSH and TRH.
(2). Two different types of goiter (enlarged thyroid)
(a). When TH is low (hypothyroidism): Lack of iodine or other factor --> low level of TH --> lack of negative feedback to HT &/or AP --> overproduction of TSH --> goiter
(b). When TH is high (hyperthroidism): Can sometimes still have too much stimulation of thyroid even in presence of TH. Problem can be over production of TRH and/or TSH (due to tumors, failure of feedback, etc.), or to over stimulation of TSH receptors by other factors. See Graves disease below.
(3). Graves disease = antibodies to TSH receptors act as agonists of TSH. (Case of (b) above). Reminder:
agonist = acts like -- or has same effect as -- normal ligand
antagonist = blocks action of -- or effect of -- normal ligand
(4). What does thyroxine do? Raises BMR and is needed during childhood for brain development.
(5). How is thyroxine made? By modification and rearrangement of tyrosines in thyroglobulin (TG) -- see handout 15A.
protein (TG) made on RER --> Golgi --> vesicles
TG stored in lumen of gland
I- taken up into gland; I added to tyrosines of TG in lumen; one modified tyrosine added to OH of another.
Degradation of TG in lysosomes --> releases T4 or T3 --> diffuses out of cell across membrane. Acts like a steroid. (For structures see handout or texts.)
(6). 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.
Try problem 7-5 & 7-9. (If you have time, there are additional problems on this topic -- most of problem set 7. )
How do you use hormones to control homeostasis?
III. Introduction to Physiology & Multicellular organisms
A. Single cell Life Style vs. Multicellular
1. Single celled organisms
a. Surrounded by external environment -- Can't change or regulate it
b. Have one basic function -- grow and multiply
c. Respond to external conditions (since can't change them) to maintain optimal intracellular state
(1). Pick up and/or dump what is necessary for metabolism
(2). Keep intracellular conditions (pH, level of amino acids, oxygen, etc.) as constant as possible and expend minimal energy by adjusting rates of transcription, enzyme activity, etc.
d. Note no specialization: each cell does all possible functions
2. Multicellular organisms & Homeostasis
a. Each cell in organism surrounded by internal environment. Extracellular fluid that makes up internal environment is composed of:
plasma = liquid part of blood = fluid between blood cells
interstitial fluid = fluid between all other cells
b. Organism as whole can regulate composition of internal environment (milieu); therefore can maintain relatively constant external environment for each cell. Process of maintaining a relatively constant internal environment (of whole organism) = homeostasis.
c. Each cell has two basic functions
(1). Grow or maintain itself as above
(2). Specialized role in maintaining homeostasis of whole organism
d. Cells are Specialized. Maintenance of homeostasis requires co-operation of many different cell types, not just circuits within a single cell.
Summary of Above:
|Unicellular Organisms||Multicellular Organisms|
|What surrounds cell?||External environment||Internal environment of organism|
|Can organism regulate what surrounds each cell?||No||Yes|
|How many functions of each cell?||1||2|
|Is cell specialized?||No||Yes|
B. Organization -- How are cells set up to co-operate in a multicellular organism?
1. Cells, Tissues & the 4 major tissue types -- see lecture #4, & Purves 41.2 & 40.3 (40.2, 40.3, & 40.4).
a. Made of (different kinds of) tissues.
b. Example: lining of GI tract. Has layers -- epithelial, connective, muscle, and nervous tissue; these serve primarily for absorption (of material from lumen), support, contraction, and regulation respectively. (See handout 15B or Purves fig. 41.2 (40.2)) The blood (a type of connective) doesn't really fit in this classification -- serves for transport of materials in and out.
3. Systems -- Group of Organs --> body or organ system. Work together to maintain homeostasis for some component. See Purves 41.1 (40.1). Number of systems depends on who's counting. Usual # is 8-12; see Purves Table 41.1 (40.1) for a list.
III. How is a component of the internal milieu regulated?
A. Let's look at a specific example, namely blood glucose. The see-saw view. See handout 15B or Purves 50.19 (50.20).
1. Have a regulated variable -- glucose level in blood
2. Need a sensor (or receptor) -- to measure levels of regulated variable (glucose)
3. Need effector(s) -- to control levels of regulated variable (glucose) -- usually have two effectors that act in opposing ways.
Note: The term "effector" is used differently in molecular biology and in physiology. In physiology, it is usually used to mean "a tissue or organ (like muscle or liver) that carries out an action and thus produces an effect." In this example, the effectors = structures that act to raise or lower the blood glucose. In molecular biology, the term "effector" is usually used to mean "a modulator of protein function." A modulator = a small molecule (like an inducer, enzyme activator etc.) that binds to a protein, alters the shape and/or function of the protein, and thus triggers an effect.
4. Have a set point -- the level the regulated variable (blood glucose) should be. Set point is also some times used to mean the level at which corrections (to raise or lower the value) kick in.
In most cases, there is no difference between these two definitions of set point. In some cases, the desired value (first definition) and the value at which corrections occur (second definition) may be different. For example, there may be two cut-off points-- upper and lower, that bracket the desired level of a regulated variable. At levels above or below the respective cut-off points, messages are sent to the appropriate effectors to take corrective action. The term "critical values" is sometimes used instead of "set points" to describe the cut-off point(s).
5. Negative Feedback -- system responds to negate changes from set point. (In positive f.b., system responds to change by making it bigger and bigger until --> boom!)
6. Value of regulated variable does not remain exactly constant, but stays within narrow limits.
See problem 5-1 & 5-2 a & b.
Next Time: Another example and a more detailed look at the glucose circuit.