C2006/F2402 '09 OUTLINE OF LECTURE #21

(c) 2009 Dr. Deborah Mowshowitz, Columbia University, New York, NY. Last update 04/12/2009 03:34 PM .

Handouts: 21A. Endocrine vs Exocrine Glands & catecholamines, 21B (Hormones Overall), 21C (Thyroid, catecholamines).
This topic is not covered in Becker. It is covered in Sadava/Purves. If you want a more detailed treatment, any physiology book will do. There are lots of good physiology books available; the one by Sherwood has been used here for the last few years. The texts by Vander or by Silverthorn are widely available and are also quite good. There is an endocrinology book on line through Pubmed. Go to books to see the list of books available or to search by topic. Also don't forget about Kimball's biology pages.

I. Wrap up of Homeostasis as needed

II. Introduction to Hormones (Endocrines) & Growth Factors

    A. How to describe or classify hormones?

1. Many Possible Classification Schemes -- Hormones can be classified by effect, chemical nature, source (which gland?), target cells, etc. etc. See Topic IV (for reference) for a extensive list.    

2. Today: We will look at (1) processes controlled by hormones,  (2) the major hormone producing glands, (3)  details for specific hormones.

    B.  Summary of typical hormone roles and examples.  See Becker Table 14-3 or Sadava fig. 41.5 (table 42.1) for a list of hormones by type of function (Becker) or by source (Sadava).

1. Stress response -- cortisol, epinephrine. Regulate heart rate, blood pressure, inflammation, etc.

2. Maintenance of Homeostasis -- insulin, glucagon. Regulate blood glucose/energy supplies and concentrations of substances in general. Maintain more or less constant conditions = homeostasis.

3. Regulation of episodic or cyclic events -- estrogen, insulin, oxytocin -- regulate lactation, pregnancy, effects of eating, etc.

4. Growth/overall regulation -- growth factors, tropic hormones  -- regulate production of other hormones. (Note: not all GF's are endocrines.)

    C. Overview of Major Glands & Hormones -- see handout 21B for overview. For a complete list see Sadava fig. 41.5 (Table 42.1)

1. Pancreas

a. endocrine gland -- secretes glucagon and insulin into blood -- These control blood sugar balance, as explained last time.

b. also exocrine gland -- secretes digestive enzymes through duct to GI tract.

What's the difference between endocrine & exocrine glands? See handout 21A.

(1). Exocrine Gland

  • When gland forms, epithelial layer leaves duct to outside.

  • Secretion from gland flows into duct outside or lumen.

  • Examples:

(i) sweat, mammary & tear glands secretion outside
(ii) stomach glands & pancreas → secretion lumen.

(2). Endocrine Gland

  • When gland forms, epithelial layer pinches off leaving no duct

  • Secretion (hormone) from gland enters blood.

  • Example: gonads, pancreas, adrenal.

(3) Both types get precursors for secretions from blood

c. Regulation -- secretion of glucagon/insulin controlled by blood sugar levels and by input from sympathetic (in response to stress).

2.  Adrenal Medulla & Cortex See Sadava fig. 41.11 (42.10).

a. Medulla (nervous)

(1). Stimulated by nerves

(2). Derived from neural tissue; part of autonomic NS.

(3). Secretes compounds that can act as transmitters (when signal cell to cell) but act as hormones (neuroendocrines) here -- are released into the blood.  Note same compound can act as a transmitter or a neuroendocrine.

(4). Major hormone = epinephrine (adrenaline); also secretes some norepinephrine (noradrenaline)For structures see handout 21A. More details in III below.

(5). Receptors. Receptors for these hormones/transmitters are same adrenergic receptors (α & β) discussed previously.

b. Cortex (epithelial)

(1). Stimulated by a hormone (ACTH)

(2). Derived from epithelial tissue

(3). Produces steroids  = corticosteroids. For structures see Sadava fig. 41.12 (42.11).

(4). Part of HT/AP axis; more details below.

3. Hypothalamus (HT)

a. Inputs: Neuroendocrine cells in HT produce hormones -- in response to 3 inputs -- neuronal, hormonal, & local conditions. (HT has sensors for some variables such as temperature, osmolarity.)

b. Outputs: To pituitary (also called hypophysis)

    (1). To anterior pituitary (AP); also called adenohypophysis

    (2). To Posterior pituitary (PP); also called neurohypophysis

c. Details of structure and HT hormones below.

4. Post. Pit. (Sadava fig. 41.6 (42.5).

a. Hormones =  ADH = antidiuretic hormone (aka vasopressin) and oxytocin.

(1). ADH. Affects (primarily) water retention; has 2 names because discovered twice from different effects. Details of action to be described when we get to kidney. (Works through IP3 or cAMP.)

(2). Oxytocin. Affects milk ejection, uterine contractions -- works (at least in part) through IP3 to affect Ca++ and therefore contraction

b. Origin/action of hormones: Peptides are very similar in structure (homologous = share common evolutionary origin)  but bind to different (G protein linked) receptors dif. effects.

5.  Anterior Pit -- Hypothalamus (HT) / Pituitary Axis

a. HT/Ant. Pit -- 3 stages

(1). HT hormones (releasing factors) that signal the AP. Hormones go direct to AP through portal vessel (details below).

(2). AP (anterior pituitary) → tropic hormones (ACTH, LH, etc.) that signal to glands (endocrine tissue)

(3). Glands lipid soluble hormones (steroids & TH) which control their target organs. Overall:

 HT releasing hormone AP   tropic hormone   TARGET GLAND hormone TARGET TISSUE action.

b. Example: How HT controls adrenal cortex


(1).  HT secretes corticotropin releasing hormone (CRH)

(2.) Ant. Pit responds by secreting ACTH (adrenal cortex tropic hormone; also called adrenocorticotropin) into general circulation

(3). ACTH stimulates adrenal cortex to produces three major types of steroids  = corticosteroids. For structures see Sadava 42.12 (41.11) .

(a). Glucocorticoids. Ex: cortisol -- involved in long term stress response (after epinephrine wears off) -- has multiple effects/targets, for ex. suppresses immune system.

(b). Mineralocorticoids. Ex: aldosterone -- regulates salt balance (to be discussed when do kidney)

(c). Sex Steroids  -- cortex produces low levels of sex hormones (both androgens and estrogens) in both sexes post puberty. That's how females get 'male' hormones and vice versa.

c. AP also  → "other hormones" (GH, Prolactin, etc.) that signal to nonendocrine tissues

6. There are other glands/hormones -- the list so far is not exhaustive but covers most of the major players. See texts for complete lists.

It is worthwhile to memorize most of handout 21B in order to keep all the hormones and glands straight.

III. Details of HT/Ant. Pit. Axis

      A. Structure -- Two parts of pituitary (AP and PP) develop and function separately; connected differently to HT.   

1. Ant. Pit. (epithelial)

        a. HT connected by portal vessel to AP. See handout 21B and/or Sadava  fig. 41.7 (42.7).

        b. Hormones released from HT into the blood travel through portal vessel direct to AP.

2. Post. Pit. (nervous) 

a. Some cells of HT have bodies in HT and axons/terminals in posterior pituitary.  (Sadava fig. 41.6 (42.5).

b. Release hormones (neuroendocrines) from endings (terminals) in post. pit   blood supply.

    B. Hypothalamic Hormones

1. Outputs (to AP): Some cells in HT release hormones from HT itself. (As vs. cells that connect to post. pit.)

a. Release hormones into portal vessel (see above) that goes direct to anterior pituitary. See Sadava 41.7 (41.7) and handout 21B

b. Hormones are release factors. Hormones released by HT affect production/release of other hormones by ant. pit.

c. Affect on release -- 'release factors' can be stimulatory (RH's such as ACTH-releasing hormone) or inhibitory (IH's such as prolactin release-inhibiting hormone = PIH)

d. All HT hormones (except PIH = dopamine) are peptides/proteins.

2. Outputs (to PP):  Some cells in HT release hormones (ADH & oxytocin) from nerve endings in PP. Hormones are peptides; made in cell body, packaged in vesicles, vesicles travel down MT's to end of neurons, hormones released by exocytosis.

3. Additional info on dopamine (DA) & related compounds  = catecholamines

a. Structures: See handout 21A 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.)

b. Receptors: There are multiple receptors for all of the catecholamines. Receptors are classified by their ligands and response to drugs.

    (1). Dopamine has its own receptors, separate from the adrenergic receptors (for epi and norepi).

    (2). 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.

c. 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 Previous lectures & problem 6-21 and 6-22 for examples of different responses to epi due to diff. receptors. For an example of the effects of dopamine, see problem 6-24.

   C. Hormones of Anterior Pituitary

1. Table of Major Hormones of AP -- details below -- see handout 21B

Tropic (or Pseudo-Tropic) Hormone(s)
All are Peptides

Target Organ

Hormones/Secretions Made by Target Organ

ACTH (adrenal cortex tropic H.) or adrenocorticotropin

Adrenal Cortex

Glucocorticoids, Mineralocorticoids & sex steroids*

Gonadotropins -- LH (Luteinizing H.) and FSH (follicle stimulating H.)#


Estrogens, androgens & progesterone*

TSH (thyroid stimulating H.) or Thyrotropin



GH (Growth H.) = somatotropin

Liver (& others)

Insulin-Like Growth Factors
(ILGF 1 & 2) = somatomedins


Mammary Gland


* All lipid soluble hormones travel through the blood attached to plasma proteins.

#FSH stimulates Sertoli & Granulosa cells; LH stimulates Leydig & Thecal cells.

2. Tropic Hormones

a. Made by ant. pit and influence other endocrine glands. All peptides

b. Release:  controlled by hormones from HT

c. Effect on target tissue

(1). Effect: Usually cause release of another hormone

(2). What is released? Hormones released by targets are steroids or act like them (thyroxine)

(3). Mechanism: All tropic hormones work through G protein linked receptors and cAMP.

(4). Question: Where are the receptors (for the appropriate hormone) on the AP? Endocrine glands? Target cells?

d. Three major tropic hormone types -- each type named after its target -- see handout 21B & table above.

See problem 7-4. (Skip choice 5 for now.)

3. 'Other Hormones 'of ant. pit.

a. GH and prolactin -- "pseudo tropic" hormones -- both peptides.

(1). Structure & mechanism: Similar in structure to each other (homologous) and use a special type of TK receptor

(2). Release: Release regulated by release/inhibitory factors from HT.

(3). What is released from target cells? Stimulate production of secretions, but not from endocrine glands.

(a). 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.)

(b). Prolactin stimulates mammary (exocrine) gland to produce milk. (Need oxytocin to eject the milk.)

Hormone (from AP)   Receptor & 1st Target   Secretion by 1st Target   Final Target
Tropic Hormone GPCR in endocrine gland endocrine (steroid or TH.) blood
Pseudo Tropic Hormones            
    GH (somatotropin) TKR in Liver* ILGFs blood
    Prolactin TKR in exocrine gland milk outside

* GH also effects other tissues -- some respond directly and some make ILGFs that affect other tissues/cells. ILGFs make by tissues other than liver are paracrines.
TKR = Tyrosine kinase receptor; GPCR = G protein coupled receptor

Try problems 7-1 & 7-13.

b. MSH (melanocytye stimulating H) etc.

(1). 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.

(2). 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.

(3). Function: Function of these hormones is relatively obscure. MSH may be involved in control of body weight as well as pigmentation.

(4). Protein Precursors: 'pro-hormones' & 'pre-pro-hormones':

(a). Many hormones are made as inactive precursors = pro-hormones. Example: pro-insulin. 

(b). 'pre-pro-hormone' = pro-hormone with its signal peptide still attached = sequence that gene codes for.

(c). Some enzymes are also made in an inactive forms (called zymogens) -- for example, trypsinogen, fibrinogen. Zymogen or pro-hormone has amino acids that must be removed to give fully active product (insulin,  typsin, fibrin, etc.).

Try Problem 7-2 & 7-4 if not yet done, but skip choice 5 (of 7-4) for now.

    D. Regulation of HT/AP Axis

1. General case:  See Sadava fig. 41.8 (42.8)

a. The cascade: 

 HT RH AP   tropic hormone   TARGET GLAND hormone TARGET TISSUE action.

b. Regulation: Hormone from target gland (thyroxine, sex steroids, etc.) has negative feedback effect on  AP (& also in some cases on HT).

2. Specific case: thyroxine production (See handout 21C)

a. The cascade:


b. Regulation

(1). Negative Feedback: TH inhibits production of both TSH and TRH. (Where are the receptors? On cell surface or intracellular??) Primary effect is at AP -- reduces response to 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. See Sadava fig. 41.9  (8th ed)

(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

c. What does thyroxine do? Raises BMR and is needed  for normal alertness and reflexes. Needed during childhood for brain development.

d. How is thyroxine made & stored? By modification and rearrangement of tyrosines in thyroglobulin (TG) -- see handout 21C or Sadava 41.9 (8th ed). How is TG made & TH released from it ?

  • 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.

e. 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.)

Try problem 7-5 & 7-9. (If you have time, there are additional problems on this topic -- most of problem set 7. )

IV. How to Keep Track of Hormones --  How to Classify Hormones & Growth Factors (or Signal Molecules in General). The following is meant as a check list to help you keep track of the various signal molecules. It is for reference & study purposes; it will not be discussed in class.
    Some of these questions/categories overlap, and you can't answer all the questions for all the hormones, growth factors, etc., but the list helps to organize the information you do have.

1. Type of Action -- Is it paracrine, endocrine (hormone), growth factor, neurotransmitter, etc.? (See handout 12B

2. Chemical nature -- Is it a peptide, amino acid or derivative, fatty acid or derivative, or steroid? See Becker table 14-4.

3. Where is it made? In what gland or tissue? (HT? pancreas?) See Sadava fig. 41.5 (Table 42.1)

4. Target Cells -- where does it act? (Muscle and liver? Just liver?)

5. Mechanism of signal transduction

A. Location/type of receptor on target cells -- Is receptor on surface or intracellular? TK* or G protein linked?

B. Type of signal transduction -- Is there a second messenger? Which one? If none, what links receptor to intracellular events?

C. Intracellular mode of action --  what mechanism is used to get the end result? Is there a change in enzyme activity? change in transcription? both? change in state of ion channel?

6. What actually gets done? What happens?

A. Biochemically speaking: Which target enzymes, proteins or genes are affected (glycogen phosphorylase activated? Gene for enzyme X transcribed?)

B. Physiological End Result: Another hormone secreted? Glycogen broken down, & Glucose in blood up? Note the "result" may have several steps, and more than one can sometimes be considered "the end."

C. What's the (teleological) point? What overall function is served by the signal molecule's action?

1. One list of possibilities: Homeostasis, response to stress, growth*, maintenance of some cycle;

2. An alternative version of the list: Regulation of rates of processes, growth & specialization, Conc. of substances, and response to stress.

3. The 2 lists are really the same = homeostasis (control of rates & concentrations), response to stress, & regulation of  growth (unidirectional and cyclic).

* Details of TK linked receptors have not been discussed (yet) in 2009. The point so far is that they are not GPCRs, and work differently.

Next Time: Wrap up of TH, and then how salt and water homeostasis is maintained (kidney function).