CHAPTER 18 THE ENDOCRINE SYSTEM
I. Introduction to the endocrine system
A. Functions as a control system
B. Hormone secretion
1. molecules that influence the activities of other cells
2. secreted by endocrine (ductless) glands (exocrine)
C. Endocrine glands of the body:
locate
1. hypothalamus neuroendocrine organ
2. pineal gland
3. pituitary
4. thyroid
5. parathyroid
6. thymus
7. adrenal glands
8. pancreas
9. ovary/testes
10. other tissues secrete hormones:
heart
kidney
II. Hormones
A. chemical substances secreted by cells into the extracellular fluids (blood) that
regulate the metabolic function of other cells
B. derived from
1. amino acids
a. peptides
b. macromolecules ( proteins)
2. sterol (cholesterol)
a. steroids
C. target cells
1. only cells with receptor for the molecule
2. cells can determine # receptors
a.can UP-REGULATE or DOWN-REGULATE
# receptors seen on the membrane
b. If constantly stimulated by a high concentration of the hormone
the cell becomes desensitized by expressing less
receptors.(Remember it is a protein made by cell)
D. receptor binding
1.lock and key
E. receptor location
1. nuclear receptor
a. hormones that affect DNA activation
1. steroids
a)lipid soluble and dissolve through the plasma
membrane and nuclear membrane to the receptor
b) Once bound to receptor the complex binds to a
DNA receptor protein that turns on DNA transcription
of the mRNA to synthesize the appropriate protein
molecule as dictated by the specific hormone.
2. plasma membrane
a. binds to membrane receptor
integral protein
b. linked to an enzyme
c. When hormone binds to its receptor, the receptor changes
shape which initiates a chain of reactions or CASCADE OF EVENTS that leads to the desired response of the cell.
Includes a second messenger inside the cell (1st messenger is the hormone itself)
d. 2nd messengers
common : cyclic AMP also in NT
Adenylyl cyclase: enzyme associated with receptor may be linked with a G protein can release energy for the reaction to make cAMP by removing a P from GTP acts like ATPase to cleave off P
This makes cyclic AMP from ATP. This messenger
can do many things within a cell. In other words cAMP does not mediate a single response but is still dependent on the specific desired response of the hormone.
One response is protein kinase (PK) activation - many different types PK. The one that is activated is specific for a particular hormone. This enzyme will phosphorylate another protein or adds a phosphate group to it. If a phosphate group is added it can make that protein either functional or nonfunctional (activates or inactivates)
EX.
Epinephrine binds to fat cell - release energy for the fight or flight response - It binds to plasma membrane receptor and a cascade of enzymatic reactions take place with the final step being breaking down stored fat to be used to make ATP.
Other hormones may use inositol trihosphate (IP3) that triggers entry of CALCIUM as second messenger into cytoplasm - release from ER.
The response of the cell is dependent on the calcium levels.
Calcium levels in extracellular and intracellular fluids is under tight regulation because of its role as a signal - spikes can be seen if you label calcium with a fluorescent molecule and then measure calcium spikes in response to administration of a hormone.
F. Half-life
1. How long hormone is in circulation
a. seconds to 30min for peptide hormones
2. If steroid and the effect requires protein synthesis the cellular response may require hours to days
3. prohormone - secreted in inactive form must be cleaved by an enzyme to become active (may have preprohormone).
If enzyme is absent then functional hormone cannot be made.
4. response to the hormone may linger for 20 min to hours
5. blood levels under tight regulation
negative feedback responses
III. Hormone Release
A. Endocrine gland stimulation:
1. hormonal
hypothalamus - pituitary - hormone itself or stimulate another endocrine gland
blood levels of hormones regulate release of stimulating hormones from pituitary if high inhibits if low releases
2. humoral
substances in blood calcium levels with calcitonin PTH
3. neural
nerve fibers stimulate release
adrenal medulla - epi sympathetic nervous system
4. hypothalamus - autonomic control center of homeostasis of many body functions - rhythyms, thirst, temp therefore connection between body stimuli and response to regulate is apparent via neuroendocrine adjustments
IV. ENDOCRINE ORGANS
A. Pituitary gland HYPOPHYSIS - to grow under
1. attached to brain via INFUNDIBULUM stalk
2. Lobes
a. Anterior adenohypophysis glandular tissue
b. posterior - neurohypophysis - storage
3. hypothalamus brain connection - sensory input
regulates secretion of ant pituitary by
secretion of RH and IH
post pit neural signals to release stored hormones
that were made by specific neurosecretory cells of hypothalamus
4. Anterior pituitary hormones
a. separate class: prohormone must be activated by specific enzymes pro-opiomelanocortin
melanocyte stimulating hormone
and opiate derivatives: endorphin, enkephalin
b. 6 hormones secreted by cells of ant pit
4 TROPIC HORMONES regulate hormonal functions of other endocrine glands
HYPOTHALAMUS
TRH, GHIH 1. TSH -- thyroid
CRH 2. ACTH - adrenal adrenocorticotropic
GnRH gonadotropins 3. FSH
GnRH 4. LH ovaries, testes -- estrogen, testost
GHRH,
GHIH-Somatostatin 5. GH all cells
PRH,PIH 6. PRL lactation
c. function of ant pit hormones
1. GH
a. secreted by somatotropic cells of ant pit
b. anabolic hormone: growth, cell division
1. particularly on bone- epiphyseal plate growth
2. Sk M - increase mass
3. protein synthesis: increase uptake of a.a. by cell
mobilizes fat increase f.a. in blood
decrease glucose uptake helps control
blood glucose levels
c. somatomedins - growth effect of GH promoted by these proteins made by liver
d. diurnal cycle of secretion
highest levels during evening sleep
e. secretion normally decreases with age
f. hypersecretion of GH
tumor of ant pit
child- gigantism 8 ft
adult - acromegaly, affects bones of hands, feet, face
g. hyposecretion of GH
adult tissue atropy, premature aging
child- pituitary dwarf 4 ft proportion
diagnose early - give GH supplement
GH studies to decrease aging
if low levels of GH may also have other low ant pit hormones
2. TSH also called thyrotropin
a. normal development and activity of thyroid hormone
b. secreted by thyrotropic cells of ant pit
c. stim by TRH of hypothalamus
d. regulated by blood levels of thyroid hormones
negative feedback
3. ACTH adrenocorticotropic hormone
a. stim the adrenal cortex to release corticosteroids
glucocorticoids, mineralocorticoids
stressors
b. secreted by corticotropic cells of ant pit
c. stim by CRH corticotropic of hypothalamus
d. diurnal release highest a.m. after getting up
e. inhibited by corticosteroid blood conc
4. Gonadotropins 2
a. secreted by gonadotropic cells of ant pit
b. onset puberty, GnRH of hypothalamus stim gonadotropin
FSH gamete production - egg, sperm
LH hormonal production, ovulation
stim interstitial cells of testes to secret
testosterone also called Interstitial cell-
stimulation hormone ICSH
c. E, T regulate FSH LH levels neg feedback mechanism
5. PRL prolactin
a. human function in production of milk in mammary gland
b. secreted by lactotropic cells in ant pit
c. release regulated by
PRH PIH- dopamine
low estrogen stim PIH
high est stim PRH Stim Prl
d. hyposecretion - no lactation
e. hypersecretion - inappropriate lactation
sigh of adenohypophysis (ant pit)
D. Posterior Pituitary neurohypophysis
neurons of hypothalamus produce and stored here
1. oxytocin
a. stim uterin contraction
up-regulation of oxytocin receptors on sm muscle of uterus
at end of pregnancy
b. let-down reflex - release of milk
c. + feedback mechanism
Pitocin to induce labor
also to help stop uterind bleeding and induce
lactation
2. ADH
antidiuretic hormone ( vasopressin )
a. diuretic - increases urine
antidiuretic - decreases urine
acts to conserve water, prevent dehydration
b. target cells - kidney tubules makes cells here more
permeable to water so water is reabsorbed by osmosis
c. blood levels of solutes monitored by osmoreceptors
in hypothalamus
d. increase secretion in response to ohter stim
low BP increase BV, increase BP
e. ETOH - inh ADH as well as would excessive drinking
of water or diuretics which have action at site of ADH in kidney
f. hyposecretion of ADH
diabetes insipidus - high urine output-polyuria
(vs. diabetes mellitus - glucose in urine)
from damage to hypothalamus, trt by prevention
of dehydration
g. hypersecretion- rare, water retention, wt gain
increase osmolarity of blood
B. THYROID GLAND
1. location
a. anterior to trachea with 2 lateral lobes
b. lobes connected at isthmus
c. has highest blood flow per gram of tissue
2. follicle
a. cells filled with colloid (thyroglobulin)
b. draw:
3. parafollicular cells
a. secrete CALCITONIN
1. sitmulated by high calcium in the blood
2. acts to decrease blood calcium levels
3. inhibits bone resorption
4. stimulates calcium uptake
4. Thyroid hormone TH(a peptide)
a. thyroxine
1. T4 - 4 iodines
2. major hormone secreted
3. at target converted to T3
b. triiodothyronine
1. T3 - 3 iodines
c. action
a. has major affect on metabolic rate
b. utilization of glucose
c. more hormone higher basal metabolic rate
d. mobilizes fat
e. tissue growth and development
f. effect on BP
g. needed for normal nervous system function
d. Regulation of release of TH
1. hypothalamus
a. thyrotropin releasing hormone TRH
b. stimulates TSH release from ant. pit.
c. acts on thyroid to secrete
d. thyroxine
e. most cells are targets
5. Disorders
a. Hyposecretion (Hypothyroidism)
1. decrease BMR
2. wt gain
3. decrease HR, BP
4. goiter- thyroid tries to make thyroxine
but cannot- may be deficiency of iodine
and gland enlarges
5. myxedema
6. cretinism - childhood hyposecretion
mental retardation, short, give hormone
b. Hypersecretion (Hyperthyroidism)
1. increase BMR
2. wt loss
3. nervousness, irritability
4. increase HR, BP
5. thyroid gland autonomously producing hormone
not regulated by TSH
6. Grave's - exopthalmic goiter - pertrusion of eyeball
c. growths of thyroid gland (nodules)
can be hypo or hypersecretion
C. PARATHYROID
1. location
a. posterior to thyroid
b. pairs on both sides
2. secrete Parathyroid hormone (PTH)
a. release stimulated by low blood calcium
b. acts to increase blood calcium
1. release at bones
2. increas absorption at GI via Vit D
activation at kidney
3. increase reabsorption via kidney
3. disorders
a. hyperparathyroidism
1. releases calcium from bone
2. hypercalcemia
3. can result in calcium deposits in
soft tissues : kidney stones
calcification of arteries
b. hypoparathyroidism
1. may be removed with thyroidectomy
2. low blood calcium
3. tetany
D. ADRENAL GLANDS
1. Location
a. above kidneys
b. covered with CT capsule
2. portions
a. medulla
1. secretes catecholamines (EPI, NEPI) by
sympathetic stimulation
b. cortex
1. secretes corticosteroids
2. have affect on protein synthesis
3. adrenal cortex regions:
a. zona glomerulosa
1. mineralcorticoids
2. mineral/water balance function
b. zona fasciculata
1. glucocorticoids
2. function with metabolism
c. zona reticularis
1. glucocorticoids
2. gonadocorticoids
4. mineralocorticoids
a. aldosterone
1. major hormone
2. regulates Na ion balance
3. water goew with sodium to increase
BV and BP
4. stimulates kidney tubule cells to
reabsorb sodium
5. probably acts to produce protein carrier
6. release influenced by humoral factors
a. high potassium
b. low sodium
7. Renin/angiotensin system stimulates
aldosteronen
8. atrial natriuretic factor
ANF
a. inhibits aldosteronism
9. disorders
a. hypersecretion
1. aldosteronism
a. hypertension
b. hyposecretion
2. Addison's Disease
a. also hyposec. of glucocorticoids 5. glucocorticoids
a. reponse to stressors as well as everyday change
b. cortisol - major hormone
c. cyclic secretion
1. peak in a.m.
d. affect on gluconeogenesis
e. increases blood glucose
f. increases fatty acid in blood
g. also anti-inflammatory
h. disorders
1. hypersecretion
Cushing's syndrome
hyperglycemia, hypertension, edema, easily bruise
redistribution of fat: moon face, buffalo hump
2. hyposecretion
Addison's Disease
weight loss, low blood glucose and sodium
high potassium, dehydration, hypotension
6. Gonadotropins
a. most are androgens
1. male sex hormones - testosterone
b. small amount of progesterone, estrogen
c. most sex hormones from gonads
d. unclear function
e. female sex drive role
f. hypersecretion
1. virilization
a. masculinization of female or
prepuberty male
E. PANCREAS
1.Exocrine function
a. in digestion
b. secretion from acini
2. endocrine function
a. Islets of Langerhans
1. alpha cells - glucagon
2. beta cells - insulin
3. glucagon and insulin opposite action
a. insulin functions to lower blood glucose
hypoglycemic hormone
b. glucagon - increases blood glucose
hyperglycemic action
4. Insulin
a. 51 a.a. protein
b. secreted as pro-insulin
1. enzyme in Islets breaks to insulin
c. secretion stimulated by high blood glucose
d. results in cellular uptake of glucose
e. disorder
1. Diabetes Mellitus
a. hyposecretion of insulin
b. sugar spills over into urine
c. cannot use glucose convert to fat
d. ketones by-product of fat metabolism
e. polyuria
f. polydipsia
g. polyphagia
h. Type I - insulin dependent
i. Type II
2. hyperinsulinism
a. high insulin
b. hypoglycemia
c. can result from insulin overdose
F. GONADS
1. Ovaries/testes
2. Hormone secretion
a. ovary
1. estrogen
2. progesterone
b. testes
1. testosterone
3. Discuss further in reproductive system
G. PINEAL GLAND
1. secrets melatonin
2. inhibits onset of puberty
3. secretion responds to light
4. associated with
a. rhythmic processes
b. body temperature
c. sleep
H. THYMUS
1. size decreases with age
2. secretes
a. thymosin
b. thymopoietin
3. involved in immune development