endocrinology lecture 3+4 Flashcards
Where is calcium important for bio processes?
essential in skeleton
-important in blood clotting
-imp. for muscle contraction
-imp. for hormone and neurotrasmitter release
-excitbility of nervous tissue and to maintain TM potential of cells
What is concentration of Ca2+ in bone, and extracellular+ cellular fluid
-bone-99% of body calcium is here
-in circulation 50% is free and 50% is bound to albumin
What hormones increases Ca2+, and decreases it
Where are these hormones produced?
- PTH (parathyroid hormone)-produced by parathyroid hormones (increases level of Ca++)
- vitamin D-increases Ca++ levels
3.calcitonin produced by parafollicular cells of thyroid-lowers Ca++ levels
Where is calcium obtained in terms of food and absorbed in body.
what is absorption increased by
-obtained in diet from milk, cheese, eggs,, butter, etc
-absorbed in the digestive tract in the duodenum and upper jejunum
-by vitamin D and PTH
Where is some calcium deposited and where does it go through?
-calcium is deposited in bones (calcitonin increase Ca++ depositionin bone)
-some wil go through kidney and into the urine (Ca++ increases this loss)
-if levels are too low in plasma PTH will stimulate reabsorption of Ca++ from kidney and removal from bone
Where is parathyroid secreted from, how many glands are there?
what does parathyroid removal cause?
secreted by parathyroid chief cells
-4 parathyroid glands located on back side of tyroid gland
-severe drop in plasma Ca++ levels causing tetanic convulsions and death
What is halflife of PTH and what amino acid section is crucial?
-3-18 min halflife
-only N terminal 34 amino acids imp for full activity since that binds to PTH receptor
What are the 4 main functions of PTH release?
Increase the concentration of plasma calcium :
1. Bone Resorption: increases bone demineralization -increases Ca++in body fluids.
2. Kidney: increase the reabsorption of Ca++ in proximal convoluted tubule.
3. Vitamin D synthesis
primarily in kidney.
4.Gut: PTH and 1,25D3, facilitate the absorption of Ca++ from the gut.
What does vitamin D synthesis do for PTH?
stimulates the conversion of 25-hydroxyvitamin D3 to
1,25-dihydroxyvitamin D3 (1,25D3; biologically active form of vitamin D)
What controls PTH release?
What is PTH mechanism of activity?
What type of feedback controls calcium levels?
-controlled directly by the circulating concentration of calcium
-binds to cognate receptor on target cells
-negative feedback
What does hypofunction of parathyroid cause?
What are the treatments for each?
-hypofunction: causes low PTH levels in circulation, hypocalcemia, decrease in vitamin D, convulsions
treatment-1,25 vitamin D and calcium supplement
What does hyperfunction of parathyroid cause?
What are the treatments?
hyperfunction:parathyroid producing too much PTH, high in vitamin D, elevated Ca++ levels, more bone resoprtion and ca++ resorption in kidney, can cause cardiac arrthymia, calcium deposition on blood vessel walls
-treatment is removal of parathyroid and replacement therapy of 1,25D3 and Ca++
Where can vitamin D be found in diet?
where can it be synthesized?
-available from limited dietary sources (cod liver oil, fatty fish).
-can be synthesized from a cholesterol metabolite, so strictly speaking, it is not a vitamin.
1. UVB light + 7-dehydrocholesterol in skin.
2. 25-hydroxylation in liver followed by…
3. 1-hydroxylation in kidney and several peripheral tissues-> 1,25-dihydroxyvitamin D3
What are the 3 physiological functions of vitamin D?
What can low vitamin D lead to in adults and in kids?
- primary function: increase calcium absorption from the intestine.
- also regulates the immune system -> protects against infection, anti-inflammatory.
- anticancer properties.
-can lead to soft bone (osteomalacia) in adults and rickets in kids
what is main cause of rickets?
-inactivating mutation in the vitamin D receptor, they lack a functional vitamin D receptor
Where is calcitonin manufactured/by what?
How many amino acids are required?
What does calcitonin do?
What happens when Ca++ rises?
-manufactured by parafollicular C cells of thyroid gland
-32 amino acids
-it loweres plasma calcium by promoting Ca++transfer from bone to blood and increasing urinary excretion of calcium
–rise in plasma Ca++ increases release of calcitonin.
-decrease in plasma calcium concentration decreases the release of calcitonin
Where are adrenal glands located, where are they heavier, and what are they types of tissue?
-located adjacent to upper surface of kidneys.
-heavier in the male than in the female.
-two distinct types of tissue - cortex and medulla.
What is the comparison between medulla and cortex, where are they developed from
what do they produce
(b) Origin: Cortex: derived from mesoderm; Medulla derived from neural crest.
(c) Function: Cortex produces steroid hormones; glucocorticoids (major one being cortisol in human, corticosterone in rodents) and mineralocorticoids (e.g.aldosterone), and progestins.
-Medulla produces catecholamines epinephrine and norepinephrine & some peptide hormones (enkephalins,dynorphins and atrial natriuretic peptides).
What are the 3 different layers in the adrenal cortex?
GMA-zona glomerulosa, mostly mineralocorticoids (aldosterone).
FGC-zona fasciculata, produces mainly glucocorticoids (cortisol).
RGPA-zona reticularis, glucocorticoids, progestins, androgens & estrogens
What controsl synthesis of adrenal steroids?
What is only expressed in glomerulus, what is it specific for?
What is specific for glucocorticoids?
Synthesis of adrenal steroids controlled by pituitary hormone adrenocorticotropin (ACTH).
18-hydroxylase present only in zona glomerulosa -zona glomerulosa specific for mineralocorticoids (GMA)
17a-hydroxylase is absent in zona glomerulosa -zona glomerulosa does not produce glucocorticoids (only for FGC and RGPA)
What do steroid hormones do?
-they regulate the transcription of hormone/receptor specific target genes
Where is aldosterone produced and what does it control?
-produced in glomerulus (GMA)
-controls ion levels of Na+ by the kidney, affects K+ and H+ plasma concentration and BP
Where are glucocorticoids produced and what they do produce?
What does it control?
How does it affect the metabolism, what can this lead to?
-produced by fasciculata, produces cortisol
-it controls salt rentention,
-protein and carbohydrate metabolism by decreasing glucose uptake by muscle and adipose tissue and decrease glycolysis, and increases glucose levels (increases insulin), can lead to adrenal diabetes and eventually diabetes mellitus
-lipid metabolism-increase levels of lipolytic enzymes, leading to hyperlipidemia and hypercholesterolemia
What are the anti inflammatory/immunosupressive actions of glucocorticoids and the effct it has on bones/
-anti inflammatory/immunosupressive actions- reduce inflammation at sites of injury, cause atrophy of the lymphatic system, so reduced antibody formation and they decrease histamine (thus allergic reaction decrease)
-decrease protein bone matrix, increased loss of Ca++ from bone leading to osteoporosis
what is glucocortcoid secretion caused by?
What is feedback controlled by?
What corrects ACTH deficiency to reinstate negative feedback?
-controlled by pituitary adrenocorticotropin (ACTH) synthezied by POMC
-hypothalamus and anterior pituitary
-cortisol correct defiency of ACTH/cortisol
What does ACTH bind to?
What does it increase and activate?
What is the rhytm of ACTH, what messes up rhytm?
binds to zona fasciculata and zona reticularis
-increases cyclic AMP production
-activates steroid enzymes increasing synthsis of steroid hormones
-diurnal=min at night and max in morn, cishings and stress messes up rhythm
What does stress increase?
What does cortisol help and inhibit?
-increases release of CRH, ACTH, and cortisol
-cortisol provides energy, but it inhibits wound healing and immune disease more susceptible
What does hypofunction of adrenal cortex cause?
what does it involve?
addison’s disease (failure of adrenal cortex to produce adrenal hormones)
-due to atrophy of adrenal glands due to tb and involves meduallas and cortex
what causes cushings disease?
hyperfunction of adrenal cortex
-increases levels of ACTH usually due to pituitary tumor
-leads to excessive glucocortcoids and mineralcorticoids
Where is the pancreas?
how much of function is exocrine?
What does the endocrine function have?
-Located behind stomach
-99% of pancreas is exocrine and secretes digestive enzymes
-islet of langerhans which syntheize glucagon (25% alpha cells) and insulin (60% of cells beta cells)
What stores/is good at making glucose?
What does insulin do?
What is glucose fasting level?
-liver is good at making and storing glucose
-insulin is the only hormone that acts primarly to decrease blood glucose
-80mg/100ml
What is glucose converted in the liver+muscle cells, in the adipose tissue, and in other cells?
a)in the liver and muscle cells is converted to glycogen.
(b)in the adipose tissue is converted to fat and stored for later use.
(c)in many cells of the body is oxidized to produce energy
What causes insulin defiency, what does it lead to?
what happens to fatty free acids (FFA), and pH?
-when beta cells are destroyed, leading to diabetes mellitus, glucose accumulates in circulation
-incomplete FFA oxidation, leading to decreased blood pH and diabetic coma and even death
What does diabetes mellitus cause?
What restores individual back to normal?
-glucose spilling into urine glycosurea (urine has sweet smell), and loss of water in urine, polyurea (excess urination leading to water loss)
-insulin
What is type 1 diabetes characterized by (insulin dependence)?
What can too much insulin injection cause?
-destruction of Beta cells in pancreas (insulin is not made)
-can cause insufficient brain function, causing insulin shock/coma
What is type 2 diabetes characterized by (insulin independence)?
What is it associated with
-insulin levels are abnormally high (insulin resistance due to decrased number of insulin receptors)
-obesity due to overeating-prolonger insulin levels decrease number of receptors
What is the type of diabetes that is typically juvenile?
-type 1 usually making kids insulin dependent, beta cells dont produce insulin
How do you measure glucose tolerance?
how long does it take for blood to return to normal in working person?
-with glucose tolerance test-doing and overnight fast and seeing how you respond to glucose
-2-3 hours, in a diabetic it can take longer
What makes glucagon?
What does it do?
What other hormones can also increase glucose level?
-alpha cells of pancreas
-raises blood sugar level by promoting break down of glycogen (glycogenolysis) and synthesis of glucose in the liver (gluconeogenesis)
-epinephrine and cortisol (glucocorticoids)
What produces growth hormone (GH)
What does it increase?
Where is production of somatomedins, what are they similar to and what do they increase?
-produced by anterior lobe of pituitary, responsible for growth
-increases protein synthesis in bones, muscle, liver, kidney, etc
-in the liver under stimulation of GH, similar to insulin like growth factors 1 and II
-increase protein synthesis+growth
What are the 2 hypothalamic neurohormone feedback mechanisms for GH release?
-GRH (GH releasing hormone) also called somatoliberin stimulate GH release
-somatostatin (GH inhibiting hormone) which inhibits GH release
-both are negative feedback loops
What does excess GH cauase in kids vs adults
-kids-gigantism
adults-acromeagly
What are the primary reproductive organs in maes and females?
-gonads and testes in males
-ovariesin females
What is the 2 function of gonads?
What type of hormones do they produce
-gametogenesis-production of reproductive gamete cells, spermatiza in men and ova in females
-secretion of sex hormones-testosterone (androgen) in men, and estrogen and progesterone in females
What does estrogen do in males for bones?
What is converted in men to produce it, what does a deficency lead to?
it maintains bone density, and for proper bone growth (prevent osteoporosis)
-produced by local tissues by the conversion by aromatase of testosterone to estrogen estradiol
-defiency leads to increased body fat and sexual desire/erectile function
What secretes Gonadotropin releasing hormone (GnRH), where does it travel?
What does GnRH stimulate?
-secreted by hypothalamus, travels to anterior pituitary via hypothalmo-pituitary portal vessels
-Stimulates release of pituitary gonadotropins: follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
What do FSH and LH stimulate?
What do gonads also produce?
FSH and LH stimulate development of spermatozoa or ova, and secretion of sex steroids
-also produce inhibin protein which also feeds back to anterior pituitary
What is main function of testes, what does it produce?
How often is sperm made, where does it take place/
How long does sperm maturization take?
production of mature germ cells (spermatogenesis), and steroid hormones (steroidogenesis)
-throughout life, and spermatogenesis takes place within the coiled seminiferous tubules of the testes
-60 days to go from spermatogonia to spermatozoon
What 2 cells are crucial for sperm maturation into spermatozoa?
Whre are each of them located and what do they produce?
1.Ledydig cells, located outside the seminiferous tubules. In response to LH, Leydig cells synthesize androgens.
2. Sertoli cells, located within the seminiferous tubules. They are intimately involved with the sperm maturation process - envelop the germ cells throughout their development
What do sertoli cells synthesize?
What is spermatogenis dependent on?
How much higher does the concentration of this hormone need to be to stimulate sperm making?
What ensures a high conc.
In response to FSH, Sertoli cells synthesize Androgen Binding Protein (ABP) and inhibin
-androgen concentrations in the seminiferois tubules
-needs to be 10x higher than androgen in circulaltion
-androgen binding proteins made by sertoli cells
What are the 2 negative feedback loops that regulate androgen synthesis, what does each one stimulate release of/inhibit?
WHat type of feedback mechanism is not in men?
Hypothlamic-pituitary-Leydig cell axis: GnRH stimulates release of LH and FSH -stimulate Leydig cells and Sertoli cells. Leydig cells produce androgen, which inhibit the release of GnRH (gonadotropin relasing hormone) , LH and FSH.
(b) Hypothalamic-pituitary-seminiferous-tubules axis: non steroidal inhibin secreted by the sertoli cells inhbits FSH release only
-positve feedback loops
wWhat is fucntion of ovary?
what are the germ cells at birth called?
-produce mature eggs, and steroid hormones
-oocytes which produce whole life supply of ova
What surrounds oocytes?
What does growth into primary follicles once initaited controlled by?
-granulosa cells and a BM which make up primordial follicles
-controlled by gonadotropins and steroid hormones until follicles ovulate
What is estrogen imp. for in females?
What does secondary follicle express?
What are the steroid producing cells called, what do they collborate with to produce?
-expression of LH receptors on granulosa cells
-expresses receptors for FSH, LH and estrogens
-theca cells, which work with granulosa cells to synthesize more estrogen
What are the 2 events that follicular development leads to?
What does estrogen do the lining of endometrium
-follicular atresia- the secondary follicle that isnt ovulating will degenerate
-ovulation
-thickens lining in prep for insertion event
What does a ruptured follicle turned into a corpus luteum secrete?
What helps the formation of corpus luteum, what do they synthesize, and how long are the hormones expressed for?
-progesterone
-theca and granulosa cells (synthesizes progesteron and estrogens
-progesterone and estrogens are expressed for a few days after ovulation
