Endocrinology Flashcards
Describe endocrine signalling
Hormone secretion into the blood by an endocrine gland. Hormone is transported by the blood to a distant target site
What are the six steps of hormone communication?
1) synthesis by endocrine cells
2) release of hormone by endocrine cells
3) Transport of hormone to target site through bloodstream
4) DETECTION of hormone by a specific receptor
5) CHANGE in cellular metabolism triggered by the hormone-receptor interactions
6) removal of hormone, (typically terminates cellular response)
What are the classical endocrine organs?
Brain Thyroid & Parathyroid Heart Adrenal Glands Kidneys Pancreas Ovaries/Testis
How are the hypothalamus and anterior pituitary connected?
Via the blood vessels of the pituitary stalk
What are the 4 classes of hormones based on structure?
Peptides/proteins
Steroids
Amines
Ionic Calcium
True/False? Thyroid hormone receptors are in the same family as steroid receptors
True
What are 4 properties of hormone receptors?
Specificity
Affinity
Saturability
Measurable effect
3 mechanisms by which a hormone can exert effects on target cells?
1) direct effects on function at the cell membrane
2) intracellular effects mediated by second messenger systems
3) intracellular effects mediated by genomic/nuclear action
What are the 2 anatomically distinct tissues of the pituitary gland?
Anterior pituitary (endocrine tissue) Posterior pituitary (neural tissue)
Why are Oxytocin and Vasopressin structurally similar?
Common precursor hypothesis:
Both control smooth muscle tone (but in different ways)
What is the only non-peptidic pituitary hormone?
Dopamine (Prolactin Inhibiting Hormone)
What are the two hormones secreted by the posterior pituitary?
Oxytocin and Vasopressin
What are the effects of oxytocin in females?
Dilation of cervix during parturition
secretion of milk
pro-social behaviour
What are the effects of oxytocin in males?
Ejaculation of sperm
Prosocial behavior
What is the major component of the thyroid colloid?
Thyroglobulin, source of thyroid hormones
What are the thyroid hormones?
Thyroxine (T4) and triiodothyronine (T3)
True/False? Humans barely have a large enough Thyroid gland - removal of 3g is enough to cause hypofunction
False
What hormone controls synthesis of thyroglobulin?
TSH
What do thyroid hormones contain?
Iodine
What is the difference between T3 and rT3?
T3 has 2 Iodines on its first aromatic ring, rT3 has 2 iodines on its second aromatic ring (not endocrine)
How are thyroid hormones synthesized?
1) molecular iodine is used for iodination of tyrosine residues of TGB to form Monoiodotyrosine and diiodotyrosine
2) Oxidative coupling of two DIT forms T4, while one MIT and one DIT forms T3
(hormones stay linked to TGB)
Rate of all steps increased by TSH
What is the Hypothalamic-end organ axis for Thyroid hormones?
Hypothalamus: Thyrotropin releasing hormone
Anterior pituitary: Thyroid Stimulating Hormone
Thyroid: T3/T4
What happens when Iodine supply is low?
TRH/TSH levels increase, stimulating thyroid follicular cells to form a goiter
Since the thyroid cannot produce hormones without Iodine, it is a non-toxic goiter
What are the key effects of thyroid hormones? (5)
Stimulation of calorigenesis in most cells Increased carbohydrate storage Lipid change Protein synthesis Promote normal growth
True/False? T4/T3 increase BMR
True
How do Thyroid hormones work?
Like steroids, enter cell nucleus, bind receptor, and alter transcription of specific genes
Do thyroid hormones need to enter the cell to exert an effect?
No. Induces some effects just from binding membrane (there is a thyroid hormone specific receptor in the inner mitochondrial membrane)
Are thyroid hormones blocked by inhibitors of protein synthesis?
No
What is the effect of T4/T3 acting directly at plasma membrane?
Increase in uptake of amino acids (independent of protein synthesis)
Why do workers at nuclear power plants take iodine supplements?
Excess stable iodine (127I) can protect the gland by saturating the transport system and diluting the amount of radioactive iodine entering the thyroid gland
True/False? Radioactive iodine is used to treat thyroid cancer
True, and it’s real good at it
What happens if you don’t have enough thyroid hormone?
Hypothyroidism
What happens if you have too much thyroid hormone?
Hyperthyroidism
What are the 14 signs of hyperthyroidism?
Elevated thyroid hormone levels Elevated BMR Increased perspiration Rapid pulse Increased body temperature Heat intolerance Warm, moist palms Nervousness, anxiety, excitability, restlessness, insomnia Weight loss Muscle wasting Increased appetite Menstrual irregularities Exophthalmos Goiter
What are the 14 signs of hypothyroidism?
Decreased Thyroid hormone levels Low BMR Decreased perspiration Slow pulse Lowered Body temperature Cold Intolerance Coarse, Dry skin, subdermal thickening Lethargy, decreased mentation, depression, paranoia, sleeplessness, tiredness Weight gain Loss of hair, dry and brittle texture Edema of face and eyelids Menstrual irregularities Carotenemia Goiter
What are the Different types of hypothyroidism?
Primary Hypothyroidism (myxedema) - Atrophy of thyroid - Autoimmune thyroiditis (Hashimoto's) - Non-toxic Goitre Secondary Hypothyroidism - Not enough TSH (pituitary-level) Tertiary Hypothyroidism - Not enough TRH (hypothalamus-level) Infantile Hypothyroidism - Causes cretinism/retardation
What is the treatment for all types of hypothyroidism?
Thyroid supplements
What are the different types of hyperthyroidism?
Primary Hyperthyroidism - Graves disease (LATS acts like TSH) - Thyroid adenoma (produces T3/T4 regardless of TSH) Secondary Hyperthyroidism - Pituitary tumor, unregulated TSH Tertiary Hyperthyroidism - Hypothalamic tumor, unregulated TRH
What are the treatments for the different types of hyperthyroidism?
Surgery/replacement therapy
Administration of radioactive iodide to kill cancerous follicles
Antithyroid drugs (propylthiouracil) which blocks addition of iodine to TGB
True/False? 100% of Calcium in circulation is bound to albumin
False, 50% bound 50% free
Where is most of the body’s calcium stored?
Bone
What are the three main hormones involved in Calcium homeostasis and what do they do?
Parathyroid hormone - Increases circulating levels of Ca Calcitonin (C cells of Thyroid) - Lowers circulating Ca Vitamin D - Increases circulating Ca
How can [Ca] be decreased?
Deposited in bone
Excreted in urine
How can [Ca] be increased?
Absorbed from food
Resorbed from bone
Reabsorbed from kidneys
True/False? You can live without Parathyroid Glands
FALSE
What does PTH do?
Increases [Ca] in blood
- increases bone demineralization
- Increases reabsorption of Ca from kidneys
- Stimulates synthesis of Vitamin D
- Facilitates absorption of Ca from gut
How is PTH release controlled?
Direct [Ca]
What are symptoms and treatment of hypoparathyroidism?
Low [Vitamin D]
Tetany, convulsions, spasms (asphyxiation)
Treatment: administration of Vitamin D and Ca supplements
What are symptoms and treatment of hyperparathyroidism?
Caused by parathyroid adenoma High [Vitamin D] High PTH stimulates bone resorption/calcium reabsorption from kidney high [Ca] Kidney Stones Calcification of vessels Arrhythmia
Treatment: removal of affected parathyroid/replacement therapy of Ca/Vit D
True/False? Vitamin D is actually a vitamin
False
How is Vitamin D synthesized?
Dehydrocholesterol in skin + UVB
Hydroxylation in liver
Hydroxylation in kidney/peripheral tissues
1,25-dihydroxyvitamin D3
What is Vitamin D’s physiological function?
Increase calcium absorption from intestine (mainly)
Regulates immune system
Anticancer properties
How is Vitamin D synthesis controlled?
Increased when [Ca] is low (or when PTH high)
Decreased when [Ca] high
What happens when you don’t have enough Vitamin D?
Rickets
How does Calcitonin work?
Promoting transfer of Ca from blood to bone, and increasing urinary excretion of Ca
End result: decreased [Ca]
Where do the two types of adrenal tissue originate from?
Cortex: mesoderm
Medulla: neural crest
Which hormones do each of the adrenal tissues produce?
Cortex: glucocorticoids (cortisol), mineralocorticoids (aldosterone), and progestins
Medulla: Catecholamines, (nor)epinephrine
(and some peptide hormones)
What are the three zones of the adrenal cortex and which hormones do they produce?
Zona glomerulosa, mineralocorticoids
Zona Fasciculata, produces glucocorticoids
Zona reticularis, glucocorticoids, progestins, androgens, estrogens
How is synthesis of adrenal steroids controlled?
Pituitary Adrenocorticotropin (ACTH)
Why is aldosterone only produced by zona glomerulosa?
Only layer that contains 18-Hydroxylase
Why doesn’t the zona glomerulosa produce glucocorticoids?
17a-hydroxylase is absent
What is the mechanism of action of steroid hormones?
Function to regulate (increase/decrease) transcription of hormone/receptor-specific target genes
What is the physiological role of aldosterone?
Sodium metabolism - increases reabsorption of Na by the kidney
(loss of [K] and [H] in urine to balance)
What is the mechanism of action of glucocorticoids?
(cortisol) Salt retention (less than aldosterone)
Effects on protein/carbohydrate metabolism
- Synthesis of gluconeogenic enzymes in hepatocytes
Increased blood glucose levels (increased insulin secretion)
How is glucocorticoid secretion controlled?
Adrenocorticotropin (ACTH) (prohormone, POMC)
What is the mechanism of action of ACTH?
Binds to specific receptor oon zona fasciculata and zona reticularis
increase of cAMP
activation of steroidogenic enzymes leading to increased steroid release
ACTH follows a circadian cycle (lowest ad midnight, highest in morning)
What causes CRH/ACTH release?
Many stress stimuli
What is Addison’s disease and what does it do?
Hypofunction of adrenal cortex
Not enough adrenocortical hormones (due to atrophy of glands)
decreased blood sugar, lipolysis, gluconeogenesis
decreased CO
Lethal if untreated for 7 days
What is Cushing’s disease and what does it do?
Hyperfunction of adrenals
hyperplasia of adrenal cortex due to high [ACTH]
negative feedback is bypassed
Increased [glucose], [insulin], proteolysis, osteoporosis, blood pressure
What % of pancreas is endocrine?
1%, islets of Langerhans
What % of endocrine pancreatic cells are beta cells? What do beta cells produce?
60%, synthesize insulin
What % of endocrine pancreatic cells are alpha cells? what do alpha cells produce?
25%, synthesize glucagon
What are the actions of insulin?
Increases glucose uptake into cells
- in liver/muscles to produce glycogen
- in adipose tissue to produce fat (storage)
- in somatic cells for energy
What causes insulin deficiency and what happens when there is no insulin?
Destruction of beta cells leads to Diabetes Mellitus - cells cannot take up glucose efficiently and [glucose] goes way up
Occurs independently of glucose in diet because of gluconeogenesis
Fat is inefficiently used as the principle source of energy, and by products include acetone which can acidify blood and send patients into diabetic coma
What happens when you are hyperglycemic?
Glucose spills into blood, leads to loss of water (polyurea), dehydration and polydipsia
What are the two types of insulin deficiency?
Type 1: insulin dependent (not enough insulin)
Type 2: insulin independent (hyporesponsiveness to insulin)
What happens if you take too much insulin as a Type 1 diabetic?
Massive drop in blood glucose - insulin shock
What is a possible treatment for type 2 diabetes?
Proper diet and exercise
How do you measure glucose tolerance?
Glucose tolerance test
Fasting patient is given a dose of glucose and blood glucose is measured over time
What controls insulin secretion?
Several feedback mechanisms, MOST important is beta cells response to [glucose], secreting little/no insulin when low, much more when high
Gastrin/vagal impulses to beta cells can also induce insulin release
(because of this insulin rises before [glucose] rises during meals
What are the mechanisms of action of Glucagon?
Promotes glycogenolysis and gluconeogenesis
-> raises blood sugar
What controls glucagon release?
[glucose]
low, increased release
high, decreased release
True/False? Glucagon is more important than insulin
False, other hormones increase [glucose], only insulin decreases
What is another name for Growth Hormone?
Somatotropin (STH)
What does GH do?
Increases protein synthesis in many tissues, enhances aa reuptake in cells by accelerating actions of mRNA
What are somatomedins?
Produced by liver under stimulation of GH
Similar to insulin (IGF I and IGF II) stimulates growth
What does somatostatin do?
Inhibits GH release
What happens when you have GH deficiency?
Proportional dwarfism
What happens when you have excess of GH?
Gigantism (young individuals)
Acromegaly (adults)
What are the male/female sex hormones?
male: testosterone (androgen)
female: estrogen and progesterone
What is the effect of estrogen in males?
Maintains bone density, contributes to increased body fat, contributes to sexual desire/erectile function (maybe)
How is estrogen produced in males?
Locally, through aromatase-mediated conversion of testosterone to estradiol
What is the reproductive hypothalamic-pituitary-end organ axis? How is it mediated?
GnRH - > LH + FSH - > steroids, estrogens, androgens
Mediated by Inhibins produced by gonads
Where does spermatogenesis take place?
In the seminiferous tubules of the testes
How long does it take to make a mature sperm?
60 days
Which hormone do Leydig cells respond to? What do they do?
LH, They synthesize androgens
Which hormone do Sertoli cells respond to? What do they do?
FSH, Synthesize ABP and inhibin
What is ABP and what does it do?
Androgen Binding Protein, acts as a sink for androgens produced by Leydig Cells
Androgens in seminiferous tubules must be approximately __ times higher than androgen concentrations in the blood
10
Testicular androgen synthesis is regulated by two negative feedback loops. What are they?
Hypothalamic-pituitary-Leydig cell axis: GnRH stimulates release of LH and FSH - stimulates Leydig cells and Sertoli cells. Leydig cells produce androgen, which inhibit the release of GnRH, LH and FSH
Hypothalamic-Pituitary-seminiferous tubules axis: non-steroidal inhibin from sertoli cells (inhibits FSH release only)
What is the structure of the ooyte?
Primordial: oocyte surrounded by granulosa cells
Primary Follicle: oocyte grows zona pellucida
Preantral follicle: early theca cells begin to grow on outside, thicker granulosa cells
early antral follicle: antrum forms inside granulosa cells
Mature follicle: Thicc Theca cells, large granulosa cells, oocyte practically covered by antrum
What is atresia?
Degradation of unreleased follicle
What happens to the follicle after ovulation?
Becomes the corpus luteum, secretes progesterone, until it degrades (luteolysis) or becomes corpus luteum of pregnancy
What happens on the first day of menstruation?
The endometrium is sloughed off
FSH production resumes (was under -ve feedback from estrogen)
Low levels of estradiol and progesterone lead to increased secretion of what?
FSH (lack of -ve feedback loop)
What happens once FSH production resumes in the menstrual cycle?
Ovarian follicle cohort develops
FSH stimulates granulosa cells of follicles to proliferate - > estrogen production - >further stimulation of granulosa cell proliferation
What happens on day 8 of the menstrual cycle?
A dominant follicle is chosen, which produces more and more estradiol (which stimulates endometrium proliferation
Estradiol induces production of _______ in the endometrium by day 13`
Progesterone receptors
What happens to FSH and LH under moderate estradiol concentrations?
-ve feedback of FSH release
Stimulation of LH synthesis (not release) by pituitary
What happens to FSH and LH under high estradiol concentrations?
elevated estrogen concs. stimulate LH release (“Surge”)
What does are the effects of the LH surge on the follicle?
Causes the follicle to rupture and eject the ovum
What are the active ingredients of oral contraceptives?
estrogen and progesterone
How do oral contraceptive pills work?
They maintain moderate circulating levels of progesterone and estrogen to suppress the release of LH and FSH from the pituitary and prevent ovarian follicles from maturation/ovulation
What happens to the ovum after implantation?
It becomes a blastocyst which becomes aa trophoblast after implantation
What are the fates of the trophoblast and the inner cell mass of the blastocyst?
Trophoblast -> placenta
Inner cell mass -> embryo
What secretes HCG and what is it?
The trophoblast - Human chorionic Gonadotropin
What hormone does HCG act like? What are its effects on the corpus luteum?
LH, stimulates the corpus luteum to continue secreting gonadal steroids
What happens after the 12th week of pregnancy?
The placenta takes over all endocrine function
What do we measure for the immunological/biological pregnancy test?
HCG
What causes the development of breast alveoli?
Progesterone
True/False? The increased size of alveoli is the reason why breasts increase in size during puberty
False, due to fat deposition
Which hormones cause breast alveoli structures to develop?
Estrogen, progesterone, prolactin, human placental lactogen, and others
What controls milk production during pregnancy? What keeps it from being secreted?
Prolactin, high estrogen
Why does lactation become possible after parturition?
Estrogen levels decrease but prolactin remains high
True/False? Prolactin is responsible for milk ejection
False (it’s Oxytocin) Prolactin is responsible for milk secretion into the ducts
Why is the menstrual cycle inhibited while nursing is maintained?
Prolactin is continuously being produced, which inhibits the secretion of FSH and LH
How is menopause detectable hormonally?
constantly high levels of FSH
What hormonal changes occur during menopause?
Loss of estrogen/progesterone production by ovary -> elimination of LH -ve feedback loop
Which of the following is NOT a site for the production of Vitamin D? A) Skin B) Liver C) Kidneys D) Peripheral Tissues
Kidneys (C)
True/False? Caucasians produce more vitamin D than African Americans
True
How are colon cancer rates and summer surface UVB levels correlated?
Inversely
True/False? Immune cells become responsive to Vitamin D after sensing bacterial presence
True
True/False? Antimicrobial activity is linked to Vitamin D
True
