What is endocrinology?
the study of glands and the hormones they produce
What is endocrine?
hormones secreted internally
What is exocrine?
hormones secreted externally or into a lumen such as the GI tract
What is a hormone?
Greek for to set in motion, they elicit cellular responses and regulate physiologic processes through feedback mechanisms
What are the classic endocrine glands?
ppptag - pituitary, pancreatic islets, parathyroid, thyroid, adrenal, gonads
What produces a vast array of peptide hormones leading to neuroendocrinology such as dopamine and norepinephrine?
the brain
What through the production of hypothalmic releasing factors exerts a major regulatory influence over pituitary hormone secretion?
central nervous system
What stimulates the adrenal medulla?
the peripheral nervous system
The adrenal glucocorticoid (cortisol) is a powerful ________.
immunosuppressant (makes you feel sick, endocrine test = increased cortisol)
What glands do cytokines and interleukins have a profound effect on?
patg - pituitary, adrenal, thyroid and gonads
What play a role in the maintenance of blood pressure, intravascular volume and peripheral resistance in the cardiovascular system?
hormones (keep everything kosher)
What are examples of vasoactive substances that change vascular tone?
cane - catecholamines, angiotensin II, nitric oxide, endothelin
(catecholamines, angiotensin II and endothelin are vasoconstrictors and nitric oxide is a vasodilator)
What is the principle source of atrial natriuretic peptide?
the heart, it induces natriuresis at a distant organ (the kidney) aka gets you to excrete Na and pee off H2O
What produces erythropoietin by stimulating erythropoiesis in the bone marrow?
kidneys
Which hormones have kidneys as their primary target?
parathyroid hormone or PTH (sees how much Ca and Ph is in the body), mineralocorticoids (aldosterone regulates Na and K) and vasopressin (increases H2O retention)
What peptide hormones that aid in digestion does the gastrointestinal tract produce?
cholecystokinin, ghrelin, gastrin, secretin, vasoactive intestinal peptide
Which peptide hormones of the digestive tract tell the LES when to relax?
ghrelin, gastrin and secretin
Which peptide hormone of the GI tract stimulates the release of bile and pancreatic enzymes and is released from the antrum of the stomach?
ghrelin
What are the five major classes of hormones?
amino acid derivatives, small neuropeptides, large proteins, steroid hormones (synthesized from chol precursors) and Vit D derivatives
What are the different amino acid derivatives?
dct - dopamine, catecholamine, thyroid hormone
What are some small neuropeptides?
Gondadotropin-releasing hormone (GnRH), thyrotropin-releasing hormone (TRH), somatostatin, vasopressin
What are the large proteins?
insulin, luteinizing hormone (LH), parathyroid hormone (PTH)
What are the steroid hormones?
cortisol, estrogen
What are the vitamin derivatives?
retinoids (vitamin A) and vitamin D
What is the antagonist of PTH?
calcitonin (released from thyroid gland)
Amino acid derivatives and peptide hormones interact with ____.
cell-surface membrane receptors (the AP classes only make you smart on the surface)
Steroid, thyroid hormones, vitamin D and retinoids are lipid-soluble and interact with ____.
intracellular nuclear receptors
The circulating level of a hormone is determined by its ___ and its ____.
rate of secretion and its circulating half-life
After protein processing, ___ are stored in secretory granules.
peptide hormones (GnRH, insulin, GH)
As granules with peptide hormones mature they are under the plasma membrane for immediate release into the circulation. The stimulus for release is either a ___ or ___.
releasing factor or neural signal
Hormone transport and degradation dictate the ___.
rapidity with which a hormonal signal decays
Is somatostatin short-lived or long-lived? What does it effect?
short-lived, effects in virtually every body tissue with concentration and actions locally controlled (soma = body and we don't live forever)
Is TSH short lived or long-lived? What does it effect?
long-lived, specific for the thyroid gland, resulting in relatively constant serum levels
When can you measure TSH levels?
any time of day since they are secreted in discrete pulses and last fifty minutes
Are thyroids usually more deficient in T3 or T4?
T3
Understanding of the circulating hormone half-life is important for achieving _____.
physiologic hormone replacement
How long is the half life of T4? How many doses do you need to give per day?
7 days, single daily dose of Synthroid (levothyroxine) to regulate daily and for a constant hormone level
How long is the half life of T3? How many doses do you need to give per day?
1 day, given 2-3 times a day (rarely given, more dynamic serum levels)
Synthetic glucocorticoids vary in their _____.
half-lives
Does dexamethasone have a short or long half life?
long half life resulting in greater suppression of the hypothalamic-pituitary-adrenal axis (dexter lives for a long time due to his lab experiments)
Do ACTH, GH, prolactin, PTH and LH have short or long half lives?
short half-lives (<20 minutes) but profound effects when they are active
What are problems with synthetic glucocorticoids that have short half-lives?
leads to sharp peaks of secretion and decay with peak around 7 am, and only accurate way to measure is to take blood sample every 10 min or less
Why is information about short half-lives good to know?
when removing adenomas that secrete hormones in such cases such as MEN or multiple endocrine neoplasia (1, 2 and 2b)
What are hormones that circulate in association with serum-binding proteins?
T4, T3, cortisol, androgen, estrogen, IGF-I, IGF-II, GH, activin
T4 and T3 bind to ____.
thyroxine-binding globulin (TBG), then carried through body and released to receptor site
Cortisol binds to ____.
cortisol-binding globulin
Androgen and estrogen binds to ____.
sex hormone-binding globulin (SHBG)
IGF-I and -II bind to multiple ____.
IGF-binding proteins (IGFPs)
GH binds to ___.
GH-binding protein (GHBP)
Activin binds to ___.
follistatin
The binding of hormones to serum-binding proteins allows for a ___ and prevents ___ as well as restricts ____ and modulates ___.
hormone reservoir, the rapid degradation of unbound hormones, hormone access to certain sites, unbound hormone conc
______ can reduce total TH levels but free T4 and T3 concentrations remain normal.
TBG deficiency
(binding protein abnormalities exist but with little clinical consequence)
Does T3 or T4 stay in circulation longer?
T4
True or False. A bound hormone elicits a biological response.
False. Only unbound hormone can interact with receptors. A bound hormone does not interact and must be released for a biological response.
Liver disease and certain meds can influence binding protein levels or cause _____.
displacement of hormones from binding proteins
Salsalate displaces ___ from ___.
T4 from TBG (salsalate means an NSAID)
Estrogen increases ___.
TBG
What are the two major classes for hormone receptors?
membrane and nuclear
What two things do membrane receptors primarily bind to?
peptide hormones and catecholamines
What do nuclear receptors bind to?
small molecules that can diffuse across the cell membrane such as TH, steroids and vitamin D
Hormones bind to receptors with ____ and an affinity that coincides with circulating hormone levels.
specificity
____ vary greatly in different target tissues, providing one of the major determinants of specific cellular responses to circulating hormones.
receptor numbers
ACTH receptors are in the ___, FSH receptors are in the ___. Insulin and TRs are in the ___.
adrenal cortex, gonads, widely distributed and reflect the need for metabolic responses in all tissues
What are the 3 general areas that functions of hormones can be divided into?
growth and differentiation, maintenance of homeostasis and reproduction
What are some things that can cause short stature?
GH deficiency, hypothyroidism, Cushing's syndrome (too much cortisol), malnutrition, chronic illness or genetic abnormalities affecting the epiphyseal growth plates
What factors stimulate growth? Lead to epiphyseal closure?
GH, IGF-1 and TH stimulate while sex hormones (sex steroids) cause epiphyseal closure
What are the most important hormones that affect homeostasis?
TH, cortisol, PTH, Vasopressin, Mineralocorticoids and Insulin
What is the function of TH?
25% of basal metabolism in most tissues
What is the function of cortisol in regards to homeostasis?
exerts a permissive action for many hormones in addition to its own direct effects
What is the function of PTH?
regulates calcium and phosphorus levels and indirectly affects bone density and serum Ca levels
What is the function of vasopressin?
regulates serum osmolality by controlling renal free-water clearance
What is the function of mineralocorticoids?
control vascular volume and serum electrolyte (Na, K) concentrations
What is the function of insulin?
maintains euglycemia in the fed and fasted states (has to be maintained or else high or low sugar can make you diabetic or hypoglycemic)
Vasopressin (ADH) is secreted by the ____ gland primarily in response to an ____.
posterior pituitary, increase in plasma osmolality
What is a defect in vasopresssin release or response?
diabetes insipidus
What are the stages of reproduction?
sex determination during fetal development, sexual maturation during puberty, contraception, pregnancy, lactation and child-rearing, and cessation of reproductive capability at menopause
In early ___ phase, pulsatile secretion of LH and FSH stimulates the maturation of the ovarian follicle.
follicular
Maturation of the ovarian follicle leads to...
gradually increasing estrogen and progesterone > enhanced pituitary sensitivity to GnRH and when this combines with accelerated GnRH secretion triggers LH surge and rupture of mature follicle
___ is produced by granulosa cells and enhances follicular growth and feeds back to pituitary to selectively suppress FSH without affecting LH.
Inhibin
___ modulate follicular responsiveness to gonadotropins.
Growth factors (EGF and IGF-1)
Vascular endothelial growth factors and prostaglandins play a role in ___.
follicle vascularization and rupture
What type of hormone feedback regulatory systems are fundamental for the endocrine system?
negative and positive (negative feedback used most of the time)
Each major hypothalamic-pituitary-hormone axis is governed by ___ feedback.
negative feedback (Ex. thyroid hormones on TRH-TSH axis, cortisol on CRH-ACTH axis, gonadal steroids on the GnRH-LH/FSH axis and IGF-1 on the (GHRH)-GH axis)
What is the example of negative feedback using thyroid hormones?
decreased TH > increased TRH from hypothalamus > increased TSH from pituitary > increased T4 and T3 from thyroid gland
What is the primary example of positive feedback control?
estrogen-mediated stimulation of the mid-cycle LH surge since chronic low levels of estrogen inhibit while rising levels stimulate LH secretion
Most hormone deficiency is attributed to ____ caused by autoimmunity, surgery, infection, hemorrhage or tumor infiltration.
glandular destruction (Ex. take out parathyroids by accident in thyroid surgery)
Mutations in a number of horomones, hormone receptors, transcription factors, enzymes and channels can also lead to ___.
hormone deficiencies
How many parathyroid glands are there? Where are they located? What do they produce?
4, posterior to the thyroid gland, produce parathyroid hormone (PTH)
PTH is the primary regulator of ____. What does it do when it acts on the bone? on the kidney?
calcium physiology, induces calcium resorption, stimulates calcium resorption and synthesis of 1,25(OH)2D (which stimulates Ca absorption in the GI)
How does increased calcium acting through the calcium-sensing receptor and increased vitamin D acting through a nuclear receptor affect PTH?
inhibits its release and synthesis, an example of negative feedback
What is the primary function of PTH?
maintain ECF Ca conc within normal range
PTH acts directly on bone and kidney and indirectly on intestine through its effects on synthesis of ___ to increase serum calcium conc.
1,25-dihydroxyvitamin D
PTH production is closely regulated by the concentration of ___.
serum ionized Ca
Any tendency towards hypocalcemia is counteracted by an increased PTH secretion. This in turn does 2 things...
1. increases rate of dissolution of bone mineral, increasing the flow of Ca from bone into blood 2. reduces renal clearance of Ca retaining more filtered at glomerulus in ECF 3. increases efficiency of Ca absorption in intestine by stimulating production
Immediate control of blood Ca is due to PTH effects on ___, and to a lesser extent on ____.
bone (500 mg btwn ECF and bone each day), renal calcium clearance
PTH preserves Ca concentration in the blood at the cost of ____.
bone destruction