endocrinology part 2 Flashcards
specific ACTH receptor to which ACTH can bind to are found on?
zona fasciculatata and zona reticularis
what happens when ACTH binds to its specific receptor?
Stimulation of adenylyl cyclase leading to increase production of cAMP.
what happens in G protein cascade caused by binding of ACTH to its receptor?
This activates the steroidogenic enzymes responsible for the synthesis and release of steroid hormones.
when are secretions of ACTH and cortisol max during the day?
morning
when are secretions of ACTH and cortisol min during the day?
evening
what factor is extremely important to circadian rhythms?
light
what may induce a significant increase in synthesis and release of CRH, ACTH, Cortisol?
stress stimulus
how can stress be advantageous when releasing cortisol?
it provides energy and amino acids through the breakdown of tissue proteins, especially under conditions where normal feeding is not feasible.
how can stress be disadvantageous when releasing cortisol?
it prevents wounds from healing
what can prolonged stress result in?
- elevated blood glucose
- adrenal diabetes
- decreased immune response
- loss of bone
what is addison’s disease a result of?
hypofunction of the adrenal glands
what is the main cause of addison’s disease?
- athrophy of adrenal gland due to TB
- may involve total destruction of the adrenal
what are the most severe symptoms of addison’s disease due to?
deficency of mineralocorticoids
what are some symptoms associated with addison’s disease?
- decreased ECF
- decreased plasma volume
- decreased cardiac output
- acidosis
- hyponatremia
what is hyponatremia?
low sodium levels in blood
what is cushing’s disease?
hyperfunction of the adrenal glands
what happens to the adrenal cortex in the case of cushing’s disease?
hyperplasia due to increased levels of ACTH
what happens in the case of cushing’s disease?
- excessive production of glucocorticoids
- increased production of mineralocorticoids
- uncontrolled sex hormone production leads to masculinization of female
what does an increased production of mineralocorticoids lead to?
alkalosis (increased blood pH)
where is the pancreas located?
behind the stomach
what part of the pancreas is endocrine?
islets of langerhans
what type of hormones are insulin and glucagon?
protein hormones
what is the main function of insulin?
reduces levels of glucose in the blood
what is the fasting glucose level?
80 mg/ 100 mL
how is glucose transported into cells?
through active transport
what is glucose converted to in the liver and muscles?
glycogen
what is glucose converted to in adipose tissue?
glucose is transformed to fat
what happens when B cells of the pancreas are destroyed?
leads to diabetes milletus where most tissues cannot take up glucose efficiently, thus it accumulates in circulation
can accumulation of glucose in circulation occur even without ingesting glucose?
yes, due to gluconeogenesis, proteins are broken down into aa and synthesis of glucose
under conditions of diabetes what happens to adipose tissue?
its broken down into FFA and used as the main source of energy, however not fully oxidized and leaves ketoacids and BHB which leads to ketosis
what are some symptoms associated with diabetes milletus?
- decreased blood pH (Acidosis)
- diabetic coma
- death
- glycosurea
- dehydration
- thirst
at what levels of blood glucose does it begin to spill in urine?
> 180mg/100mL
what is needed to restore levels of blood glucose to normal?
insulin injections
what is another name given to type 1 diabetes?
insulin dependent diabetes
what is another name given to type 2 diabetes?
insulin independent diabetes
what are possible causes for type 1 diabetes?
destruction of B cells or defective insulin release
treatments for type 1 diabetes?
insulin injections and proper diet
or
drugs which will stimulate release of insulin
is 20-30mg/100mL of glucose enough for the brain?
no
what type of diabetes is juvenile diabetes?
type 1 generally, however with increasing obesity, type 2 has become more prominent
how to detect type 2 diabetes?
insulin levels tend to be abnormally high
what causes for type 2 diabetes
hyperresponsiveness of target cells to insulin often due to decreased number of insulin receptors
how is type 2 diabetes related to obesity?
over eating causes for prolonged levels of high insulin down regulates the function of these receptors
how can a proper diet and exercise be a treatment for type 2 diabetes?
Decreased caloric intake = decreased insulin and thereby up regulation of receptors.
The # of insulin receptors is also increased in response to frequent endurance exercise
how is glucose tolerance in diabetes?
decreased
how is glucose tolerance in hyperinsulinismn
increased
how to conduct a glucose tolerance test?
- fasted levels are tested
- given 0.7-1.5g/KG BW of glucose
- test after 1h, 2-3H
how will the graph of a normal patient look like when testing glucose tolerance?
fasted around 80mg/100mL
after 1h: Spikes up to around 130 mg/100mL
after 2-3H: returns back to normal
how does the graph for glucose tolerance differ in a diabetic patient?
fasted glucose is more elevated, blood glucose will spike more and will take much longer to return to normal
what other test can be done to measure glucose tolerance?
AIC hemoglobin concentration, levels of A1C in blood indicate glucose levels
what do high A1C levels indicate?
shows that over past few week glucose levels have been elevated; may show a sign of lack of control
regulation of insulin secretion?
B cells respond to levels of blood glucose; low= decreased insulin secretion, high; increase insulin secretion
why does insulin begin to leave the pancreas even before the blood glucose levels increase
◦ The release of gastrin and vagal impulses in response to food stimulate the beta-cellsto induce insulin release.
what cell is responsible for the synthesis of glucagon?
a cells of the pancreas
what is the function of glucagon?
Raises blood sugar by promoting glycogenolysis (breakdown of glycogen) and gluconeogenesis (synthesis
of glucose) in the liver (it mimics glucocorticoids).
◦ Increases the rate of lipolysis in adipose tissue leading to increased concentration of FFA in the circulation.
what controls release of glucagon?
levels of blood glucose
high= decreased glucagon synthesis and release
low-= increased synthesis and release
why is glucagon not as important as insulin?
because blood glucose levels can be increased by other hormones such as cortisol and epinephrine
what type of hormone is GH?
polypetide
where is GH produced?
anterior pituitary
what is GH responsible for?
responsible for growth; increases protein synthesis, enhancing AA uptake and accelerates transcription and translation of mRNA, increases rate of lipoylsis
where are somatomedins produced?
in the liver under stimulation of GH
which one between GH can somatomedins can increase protein synthesis?
both
which one between GH can somatomedins can increase lipolysis?
GH only
which one between GH can somatomedins cans timulate growth?
only IGF-1 and IGF-2
what hormones are stucturally similar to insulin and are named IGF 1-2
Somatomedins
under what conditions may somatomedins bin to insulin receptors and vice versa?
under high concentrations
how is GH release controled?
through a complex feedback mechanism involving GRH and somatostatins
what are somatostatin?
they inhibit GH release
what happens if person is GH deficient?
decreased physical growth
what happens if person has excess GH ?
in youth: gigantism
adults: acromegaly
what are the primary reproductive organs?
testes and ovaries
what type of reproductive organ are breasts considered to be?
accessory reproductive organs
what are the 2 mains functions of gonads?
- gametogensis
2. secretion of sex hormones
what is estrogen in males required for?
- bone maturation and density
- decreased body fat
- contributes to sexual desires
where is estrogen produced in males?
locally produced by the conversion of testosterone by aromatase
what type of hormone is GnRH?
hypothalamic
neurohormone.
what is the function of GnRH
stimulates the release of pituitary gonadotropins: Follicle- stimulating hormone (FSH) and luteinizing hormone (LH).
what do FSH and LH stimulate?
the development of spermatozoa and ova, as well
as the secretion of sex steroids.
what hormone other than sex hormones is also produced by gonads?
inhibin
where does spermatogenesis take place?
within the coiled seminiferous tubules of the testes.
how long does the maturation process of the spermatogonia take?
~60 days
what are the cells that are critical to the maturation of the sperm?
leydig cells
sertoli cells
what do sertoli cells do?
they are involved in sperm maturation, they envelop the germ throughout maturation
where are sertoli cells located?
within the semiferous tubules
what do leydig cells do?
synthesize androgens in response to LH
where are leydig cells located?
outside the seminiferous tubules
what do sertoli cells synthesize in response to FSH?
ABP and inhibin
what is spermatogenesis critically dependent on?
androgen concentration in seminiferous tubules,
should be 10x greater than in circulation
what ensures there are sufficent androgens in the seminiferous tubules?
ABP
Testicular androgen synthesis is regulated by what?
2 negative feed back loops
what is the Hypothalamic-pituitary-leydig cell axis.
its the first feedback loop for testicular androgen synthesis where
GnRH stimulates release of FSH and LH.
Lh stimulates androgen synthesis in leydig cells
androgen will inhibit GnRH and LH
what is the Hypothalamic-pituitary-seminiferous-tubules axis?
its the second feedback loop for testicular androgen synthesis where the non steroidal inhibin secreted by sertoli cells inhibit FSH release
is there positive feedback in males?
no
how many non proliferating germ cells do females have at birth vs at puberty?
2 million to about 400 000
what is the primordial follicle composed of?
granulosa cells and basement membrane
what are primary follicles?
oocytes that have become bigger
what is the term used to express degeneration of oocyte?
atresia
how many mature follicles are produced per cycle?
only 1
Why are mature follicles important for the endocrine system?
they release hormones that influence the menstrual cycle
when the oocyte grows and develops, what does it elaborate?
zona pellucida (an acellular layer rich in glycoproteins)
what happens to the granulosa cells when the primordial follicle becomes the primary follicle?
the cells divide and increase to become 2+ layers
what controls the process converting the primordial follicle into the primary follicle?
FSH and estrogen
why is estrogen important in the conversion to primary follicle?
Estrogen is important for the expression of LH receptors on granulosa cells.
under what does the primary follicle develope into the secondary follicle?
FSH and LH
What receptors are expressed on the secondary follicle?
FSH, LH, estrogen
what does the follicular antrum contain
secretions from the granulosa cells
what does the mature follicle produce alot of?
estrogen
what are theca cells?
cells from ovarian stroma surrounding the follicle differentiate and become steroid producing cells
what does follicular development lead to?
- follicular atresia
2. ovulation
what is ovulation?
Rupture of follicle that leads to the expulsion of the mature oocyte into the fallopian tubes.
when does luteinization occur?
after ovulation
what does the rupture follicle transform into and what does it secrete?
becomes the corpus luteum and secretes progesterone
what cells contribute to the formation of the corpus luteum?
theca and granulosa cells
what if produced by the corpus luteum for a few days following ovulation?
progesterone and estrogen levels
under what circumstances will the levels of progesterone and estrogen not drop after a few day past ovulation?
if it has been fertilized
what is the life span of the corpus luteum determined by?
implantation or not
what happens to the corpus luteum is implantation occurs?
becomes corpus luteum of pregnancy
what is the corpus luteum of pregnancy responsible for?
The synthesis of progesterone and estrogens.
The creation of a proper endocrine environment for the
maintenance of pregnancy until progesterone and estrogen synthesis by the placenta is established.
what is the role of estrogen during pregnancy?
t works on the lining of the endometrium (lining of the uterus) to make it thicker.
what is the role of progesterone during pregnancy?
Progesterone puts in the details into the endometrium and makes it into a liveable space.
what happens if no implantation occurs?
Luteolysis
what induced luteloysis
prostaglandins which decreas LH binding
what effect does estrogen have prior to menses?
thicken the endometrium
what effect does progesterone have prior to menses?
induces the appearance of specialized
glycogen-secreting glands on the endometrium
what is day 1 considered to be?
first day of menses
how do menses begin?
when the blood vessels supplying the endometrium constrict due to low levels of circulating estradiol and progesterone.
are the ovaries active or inactive during menses?
rather inactive
what is the result of low estradiol and progesterone?
increase of FSH
decrease of non steroidal inhibin which may also lead to rise in FSH
cohort of ovarian follicles develop under the influence of what?
FSH
FSH induces the proliferation of what cells?
granulosa cells
what do granulosa cells produce?
estrogen
what happens on day 8 of the cycle?
one follicle becomes dominant and committed to further development, the rest undergo atresia
what happens on day 13?
endometrium is vert thick as the rising levels of estrogen prepare for the appearence of the corpus luteum
what do moderate levels of estradiol lead to?
Negative feedback on FSH release.
Stimulate the synthesis of LH by the pituitary and increases the
anterior pituitary’s sensitivity to GnRH (more receptors).
why is LH not released under moderate levels of estradiol?
because GnRH inhibits LH release but stimulates its synthesis, LH
accumulates in the pituitary gland.
what do high levels of estradiol lead to?
Elevated estrogen levels stimulate LH release.
Estrogen positive feedback control mechanism.
what happens during positive feedback of estrogen?
‣ Stimulation of LH synthesis by estradiol.
‣ Increased sensitivity of the anterior pituitary to GnRH leading to
increased LH synthesis.
at what day dos the LH surge occur?
day 14
how does estrogen exert negative feedback?
by decreasing GnRH and LH release.
how does estrogen exert positive feedback?
by increasing anterior pituitary sensitivity to GnRH
and LH synthesis.
how do oral contraceptive work?
maintain moderate levels of estradiol and progesterone thus supressing release of FSH and LH
under the influence of what does the follicle become the corpus luteum?
influence of LH
what happens to the endometrium under the influence of progesterone?
becomes glandular
what happens in the absence of progesterone and estrogen?
the endometrium will not fully develop and any egg that is fertilized will be lost.
what is the luteal phase of a cycle?
the 14 days during which steroids produced by the corpus luteum dominate.
after 14 days in the absence of fertilization what happens?
- The corpus luteum degenerates (luteolysis) - Steroid levels drop.
- The uterine endometrium degenerates and menstruation begins.
- The anterior pituitary increases its secretion of FSH, and we are back to the beginning of the cycle.
what happens to egg by the time its transported down to the oviduct into the uterine lumen?
becomes blastocysts
what does the blastocyst differentiate into?
placentra and inner cell mass; embryo
what does the trophoblast begin to synthesize after implantation?
HCG
what is HCG the basis for?
pregnancy tests
what is the function of HCG?
it has LH-like properties and stimulates the corpus luteum’s gonadal steroid production.
after what week does the placenta take over endocrine functions?
12th week
The fetal liver acquires an important function in the synthesis of what?
estradiol
what stimulates the growth of the alveoli?
progesterone
what is breast enlargement due to?
fat deposition under the glandular tissue
Milk production during pregnancy is controlled by?
prolactin
what do high levels of estrogen do to milk production?
stops it
after pariturition what happens to estrogen and prolactin levels?
estrogen decreases, prolactin remains high
what can be transmitted through milk?
Infectious agents such as viruses and drugs may be transmitted
from the mother to the infant through milk.
what does maintained prolactin production do to FSH and LH secretions?
inhibits it
can lactation serve as a natural contraception method?
yes, but needs to be done constantly and sufficently
what causes menopause?
Depletion of follicles results in loss of steroid (estrogen and progesterone) production in the ovary.
what are some symptoms associated with the lack of estrogen?
Hot flashes, dry vagina, restlessness, bone loss (osteoporosis - long term).
constant high levels of FSH are an indicator of?
menopause due to elimation of negative feedback loop
can fertility be restored by homonal remplacement therapy?
no
what is vitamin D3 produced from
choesterol
what bond is split by UVB to created active vitamin D?
bond 6-7
where is 1-hydroxylaze is then added?
at the kidneys
where is 25-hydroxylaze is then added?
at the liver
what are diseases that have shown vitamin D north south gradients?
Certain types of cancer (in particular digestive cancers and leukemia). ◦ Autoimmune diseases (multiple sclerosis).
◦ Infectious diseases (TB)
does altitude also impacts exposure to vitamin D?
higher altitude= greater exposure to UVB
sensor on cell wall of macrophages increased the synthesis of what?
1-hydroxylase.
what happens when an infection comes into you body>
the macrophages will begin to produce 1-
hydroxylaze, this will bind to the circulating 25-hydroxylase and create the biologically active form of vitamin D3.
is it true that D3 helps to produce own antibodies?
yes, immune response is dependent on D3 concentrations (25-hydroxylase
