endocrinology lectures 1 and 2

Intro to Endocrinology
Today we will cover the basics. Covering only some hormones and glands. Know only level we cover in class for the ones he just barely mentions; read book sections or chapters on those he emphasizes.
What are endocrine glands and what are hormones?
endocrine glands are part of 3 regulatory systems in body:
1. nervous- communication with direct wiring (nerves). Generally operate 1:1 (or 1:100) with direct connections.
2. endocrine involves chemical transfer through bloodstream and diffusion to interact with tissues.
In some cases systems merge to form neuroendocrine glands. Nerve cells secrete a product to bloodstream. Operate by dumping into bloodstream. Hormones affect only the tissues with appropriate receptors.
3. maybe immune as well.
List of hormones we will cover is under A2. Endocrinology- know acronyms.
What is a hormone?
chemical substance which is released in small quantities from certain glands (endocrine glands). These substances travel through the circulatory system to elicit response in certain tissues(target tissues or cells)
include neurohormones, but not CO2 or intracellular messengers like cAMP.
A chart here in my notes did not copy properly.
Major glands:
hypothalamus affects anterior pituitary through circulatory system.
Posterior pituitary
thyroid gland in neck –regulates metabolism
4 glands on surface are parathyroid- secrete PTH
abdomen- kidneys have some endocrine function. top each is adrenal gland. The adrenal gland has 2 distinct endocrine tissues- medulla in center part is neuroendocrine- secretes epinephrine (epi) and norepinephrine(NE). outside is cortex, secreting cortisol and aldosterone.
Pancreas- GI related with islets for insulin and glucagon. Has exocrine tissue and endocrine tissue. GI tract also secretes GI hormones. Affect digestive processing, motility, secretion pancreatic hormones.
reproductive tissues: ovaries, placenta during pregnancy, testes in male.
Neuroendocrine hormones:Nervous systems affecting hormones
Epinephrine controlled directly by nervous systems. So are vasopressin and oxytocin.
Hypothalamic releasing hormones
Hormones affecting nervous systems:
epinephrine- causes anxiety and fear.
regulation by sex hormones of sex activity- (no testes- males lose interest in sex)
3 categories of hormones: listed under B
Why categories- listed below the categories.
Liver disease can foul up endocrine systems by not producing enough plasma proteins to bind hormones in blood.
Renal disease- lose plasma proteins in leaky kidney.
Metabolism also malfunctions in renal/liver diease.
2 pages tables in handout- glands and hormones. fill in as we go.
See chart
tropic=growth.
FSH is active in males and females. So is LH.
T4- 4 iodines. T3-3 iodines. Body converts T4 to T3.
Gland makes mostly T4.
calcitonin also called thyrocalcitonin.
On table- know acronyms and other names, major functions, details of regulatory functions
adrenal medulla- regulation organic metabolism- stimulates glycogen and fat breakdown
chemical nature of epi and NE- catecholamines
major stimuli to increase or decrease secretion:
increase- stress (fear), hypoglycemia, fight or flight response.
what hormone down in hypoglycemia- insulin
opposite inhibits secretion.
4 categories in Table 2: chemical nature of hormones:
see table 2. progesterone promotes gestation.
steroids, amino acid derivatives, proteins, peptides are the categories.
Catecholamines have catechol (benzine ring with 2 adjacent OHs on the ring) R-NH2 is an amine.
Proteins arbitrarily have molecular weight more than 8000-9000 . About 70 amino acids. Proteins made in anterior pituitary, kidney, placenta.
Dopamine is not a peptide- it is a catecholamine.
GHRH- growth hormone releasing hormone.
GHIH- growth hormone release inhibiting hormone (somatostatin) statin- means hold steady.
There may be a prolactin releasing hormone. PRL suppressed most of the time by dopamine. Dopamine relased almost continuously and keeps PRL suppressed. PRL is stimulated by suckling- stop dopamine secretion. PRL goes to mammary glands for milk production. Oxytocin causes milk release. Keep these straight. Oxytocin is also stimulated by suckling.
Will not ask which are proteins and which are peptrides.
Smallest one is TRH.
Structure of steroids- all synthesized from cholesterol. All retain 4 rings ABCD. Some of side chain lopped off and you get steroids with 21 or 19 carbons. Cortisol has 21 carbons .
Estradiol- 18 Cs. There is one OH in the 17 beta position of estradiol, hence the name. Estradiol has aromatic ring. Aldosterone is different because aldehyde group on C-18. Specific enzymes make modifications. These hormones operate on specific tissues.
Synthetic pathway- see handout. Do not have to learn enzymes that make conversions. Specific tissues have specific enzymes. The point is that if a person has a genetic deficiency of enzyme, his or her ability to synthesize the final product is not there. Drugs can also block enzymes. The body senses the lack of final product and tries to make more. The first processes are driven until the blocked step. Intermediates build up and may be weakly active. Some effects may happen, but they will be weak. Some substances have different action altogether.
Mineralocorticoid- aldosterone.
Catecholamine chart- another example of hormone synthesis
4 enzymes in sequence. Dopamine is produced in hypothalamus and adrenal glands- medulla. Most converted to NE,then to Epi by PNMT. PNMT enzyme requires cortisol or corticosterone for activity. Only tissue with high enough concentration of corticoids is adrenal gland. Drainage from cortex passes through medulla before entering veins, sees high cortisol.
Do not have to draw. Know precursor and organs and what it takes to get to epi.
Hormones in blood:
Biologically important form of any hormone is unbound. Bound can’t get out of capillaries. Little peptides need to be bound to prevent filtering out in kidneys.
thyroid hormone is small.
TeBG is also called sex hormone binding globulin, or testosterone-estrogen binding globulin.
There is always equilibrium between free and bound hormone. For many hormones, the equilibrium is shifted toward bound form. Some free leaves, more jumps off proteins. Keeps free level where it should be. If you lose proteins, you’ll have problems.
3. Total concentration of hormone in plasma= free+ bound (most bound)
4. Active hormone
a. on target cells-free
b. on feedback sensors controlling secretion- free.
Biologically active form is sensed by cells regulating and producing hormone secretions.
C. Steps in Life of Hormone-
Regulators stimulate, inhibit, or have both competing. Other hormones also influence processes in endocrine cells themselves. Hormione is secreted, diffuses to plasma, bound, free or combination. Most assays measure both bound and free protein. In plasma- some excreted, inactivated, further activated,
Target cells have receptors. Receptors give specificity. How do they act(genes, transcription, 2nd messengers). Action of hormone may be feedback. Ex: insulin lowers glucose. Takes away stimulation for secretion insulin. Reaction of target tissue is also influenced by other factors. Any step shown can get messed up.
Given a scenario- think of places with potential problem or places for intervention.
Cellular mechanism of action-
receptors. High affinity receptors, mostly.
changing number of receptors will influence reactivity of target tissue. More receptors, more response.
If insulin is high for a while, body tissues react by reducing number of insulin receptors. Means bigger doses of insulin.
Receptors can change sensitivity and response capacity of tissue. Same maximum response when sensitivity changes.
Changing response capacity (see graphs of dose-response curves, page 567, text):
increase capacity- same concentration gives same half maximum response. Total response changes.
increase sensitivity-response shifts to left, meaning a lower concentration is needed for the same response.
Lots of tissues have spare receptors- hardly ever are all used.
Some hormones diffuse across the cell membrane and get to nucleus to receptor in nucleus- interact with genetic material to give response. These tend to be steroid and thyroid hormones. All other hormones act at surface to generate 2nd messengers. These
1. amplify signal of hormone-receptor complex at surface (signal cascade)
2. disperse hormone signal to variety of places in cell.
Secretory pattern of hormones- most not steady. See paper.
May be diurnal, circadian, ultraradian.
Measuring hormone does not necessarily measure activity. If data on hormone concentration does not match activity, something may be odd.
Most hormones are secreted episodically.
Cortisol stimulated by ACTH appears to be secreted once a day. See graphs. More sensitive assays- peaks early in morning, but also present at other times. Really ultradian rhythm, but it may be characterized as diurnal rhythm.
Other hormones not affected. Other patterns of secretion- testosterone in adult man does not change a lot, but has a rhythm.
LH=pulsatile secretion- changes about 50-60%.
Stimulation- induced secretion – PRL stimulated by suckling.
E and F are summary tables.
Remember there are lots of places hormone secretion, synthesis, action can be affected. Essay questions abound.

Lecture 2:
Hormonal Pathways
2. PTH goes to kidneys and stimulates activation of vitamin D to target in bone and small intestine.
examples of 3 glands and 3 hormones will be covered in lecture. Here is one:
RH to pituitary trophic hormone to peripheral glands to secrete their hormones.
Fig. 2 in handout on G. Hormonal Pathways page:
Endocrine gland inputs can be stimulatory(+) or inhibitory(-).
fig 3
2 nd gland can influence how well 1st gland stimulates to release or inhibit hormone.
One other concept:
"permissiveness"-permissive effect of hormone. Hormone allows another hormone or other signals to work much better. Ex: lipolysis. Put a fat cell in a flask. Add thyroid hormones such as T3- see nothing obvious- no release. Take next bunch and add Epi and NE- lipolytic- small amounts fatty acids released. .3rd group add T3, then epi, get large amount fatty acids released. T3 allows epi to be more potent in stimulating lipolysis.
Can’t add both hormones to flask at same time – thyroid hormone has to go to nucleus and modify gene expression. Modifying gene expression takes time. We have some T3 around all the time- makes other hormones more effective.
2 important concepts:
feedback regulation
2types: +/- feedback.
1. positive feedback- during labor and delivery. Oxytocin does not usually stimulate initial contraction. Contraction begins, then oxytocin does its task. Signal ends up in post pituitary. Baby delivered-stimulus gone. Note diagram(like on page 769, text-not in handout)- loop will have all +s.
Other + stimulus- suckling. impulse to nervous system- post pituitary- oxytocin- mammary gland- let down- suckling continues until baby is full. Other stimuli may start process. Process may begin with baby crying or if mom knows it is scheduled time to feed and begins to prepare.
2. negative feedback is far more common. End response negates stimulus that started it. 2 examples: blood glucose regulation by insulin and glucagon.
insulin and glucose-A. glucose uptake lowers blood glucose until it goes back to normal. glucagon stimulated by drop in glucose. See paper. Each is separate negative feedback system because regulation leads to negation of stimulus that started it. Counterregulatory systems like insulin and glucagon give smooth control.
Glucose tolerance test is done because it is hard to see something unless you push the system.
Initial conditions: fasting and minimally stressed. (Adapt animal to procedure). Normal animal- fasting glucose 90 mg/dL. Challenge at t=0. Plasma insulin starts at 10 microunits per mL. Goes up 5 fold. Removal of glucose removes stimulus. Insulin also turns off body’s release of glucose from glycogen stores. Insulin is rapidly cleared. Total time course is 5 hours. No insulin- blood sugar starts a lot higher, goes up. comes back to a high level because it is excreted. Be able to sit down and explain this on the test. We drew this on paper-check with somebody.
hypothalamus and pituitary:
see paper.
Above pituitary is hypothalamus.
Look at figures one and two, pages 574-575, and 4 on page 580 (All references are to the Johnson text).
neurohypophysis- is the bottom of hypothalamus. Know anterior and posterior.
Bottom of hypothalamus has capillary bed- where RH are released into "long" portal veins- probably less than 1 cm long. Short portal vessels go front to back of pituitary. 2 capillary beds separated by a blood vessel make what is known as a portal system. RH are not used up in pituitary- go to heart, and get diluted too much to be effective. Must be high concentration to regulate. Blood goes in through superior and inferior arteries. Blood leaves into venous sinuses. If you need to measure RH levels- neurosurgerons can sample venous sinuses for the anterior lobe of the pituitary.
median eminence- axon terminals release RH carried by LPV to anterior pituitary(see figures 1 and 2, pp574-575).
Anterior lobe figure 2- arterial blood picks up RH- through long portal vein- stimulates release of anterior pituitary hormone- picked up in second capillary bed- out to distribution.
Posterior gland- cell bodies synthesize and pack post-pituitary hormones. Vesicles travel down axon to post pituitary. Go by axoplasmic flow through nerve axon. Stored in post pituitary gland at nerve terminals. Cell body fires action potentials fast- axoplasmic flow is slow. Vesicles stored are released like neurotransmitters are released. Stimuli summate to give a string of action potentials- just like release of neurotransmitter at neuromuscular junction or between 2 nerves.
Vasopressin is ADH. Both nuclei make both hormones. What if you cut infundibular stalk and sealed with wax? No secretion of vasopressin and oxytocin. see p585 Johnson. After a while, excessive drinking slows. Blood vessels and capillaries grow around wound and pick up hormone at a higher anatomical place. Produces diabetes insipidus.
2 terms to know:
diabetes mellitus- type I or II – sweet urine. May have large volume due to sugar drawing water out for excretion.
diabetes insipidus- urine is very dilute. Low urea and salt. Large volume, dilute.
nonapeptide- 9AAs. Both have a disulfide bridge. ADH and oxytocin have overlapping biological activity- do similar things. ADH has some weak oxytocin-like activity. Tiny moelcules are synthesized as larger molecules. Stored, cut out. Neurophysin is other cut part. Secreted at post- pituitary nerve terminals. Neurophysins have no function as hormones as far as we know (see 583 Johnson for putative function).
Oxytocin increases contractility of myoepithelial cells in mammary glands. Also stimulates uterine muscle. Myoepithelial cells surround alveoli containing milk. Oxytocin comes from blood and stimulates cells to contract to force milk out to capillaries and ducts. Epithelial cells make milk. Myoepithelial cells move it.
PVN and SON of hypothalamus send action potentials down for milk ejection or letdown. Also effects utierine smooth muscle.
ADH increases contractility of arterial smooth muscle (pressor effect to increase blood pressure).
ADH also effects kidneys to increase water reabsorption in collecting duct and distal tubule. Antidiuretic action.
E. control of secretion
ADH 2 main stimuli- decreased plasma volume or increased plasma osmolarity. osmolarity receptors in hypothalamus.
See fig 4 on extra sheet.. X on bottle- not enough water. Without water, water concentration decreases. Osmolarity increases.ADH increases. ADH increases water permeability and increases water reabsorption in kidney. Decreases water excretion.
Fig 5 more water in –see arrows.
Fig 6- baroreceptor mediate pathway.
Note sensible relations of stimuli to cause increase or decrease in secretion. intermediate lobe- not discussing.
Anterior pituitary gland
see sheet.
Most are tropic hormones- cause growth. Somatotropin causes body to grow. TSH increases size of thyroid. LH and FSH male and female gonads.
ACTH is peptide.
POMC is synthesized as a larger molecule and cut down. ACTH activity- cut from C to N terminal end and measure activity- only need 20 of 39 amino acids.N terminal region is biological activity. C terminal end is where immunologic activity is (antibodies will be toward C end). If abnormality is at the N end, immunoassay will say the protein is normal.
alpha MSH structure is within ACTH- melanocyte stimulating hormone in 1st 13 AAs ACTH. Take frog, put in aquarium with a little water, bright room- frog skin is light. inject with ACTH- turns dark. Just like if frog goes from sand to leafy background. In nature the change happens via MSH. Possible human applications. Humans with high ACTH have complexion changes.
Cell types producing ACTH can be determined by staining. It varies. May be acidophilic 50% (GH. PRL from somatotrophs, lactotrophs), basophilic 20-25% (TSH, LH, FSH- thyrotrophs, gonadotrophs) chromophobes(10-15%- corticotrophs).
Histology:
see paper.
hCG produced during the 1st trimester of pregnancy. human chorionic gonadotropin.
Tests need to measure beta subunit.
EPT tests do this for B subunit hCG.
Actions and secretion- see chart.
See fig 7 and fig 8.
ACTH provokes actions of cortisol.
Remove adrenals- no cortisol. Treat with cortisone- adrenal glands decrease in size. Glands do not synthesize as much cortisol due to atrophy- later, when it is needed. it can’t be made. To get around this problem, you taper the dosage or give ACTH. Drawback to a protein like ACTH-must be given by injection.
Lots of notes were taken on paper by drawing up and down arrows on charts. You need to get those from someone who was there.