endocrine control 2 Flashcards
corticotropin releasing hormones
act on anterior pituitary to release adrenocorticotropic hormone
adrenocorticotropic hormone acts on the adrenal cortex mineralocorticoids (aldosterone) glucocorticoids (cortisol) androgens
cholesterol
has a large side chain preventing it from being transported into the mitochrondria
how to get cholesterol into the mitochdondria
cholesterol dose chain cleavage enzymes
cholesterol once into the mitcochodnira
pregnenolone
pregnenolone converted into
any steroids
depends on assembly of different enzymes available in the cell
2 main steps of steroidoegensi
- cholesterol changing to pregneolone
2. pregnenolone changing too all other steroids
cholesterol side chain cleavage
P450scc = cholesterol side chain cleavage (rate limiting step) enzyme
transported by AtAR = sterodssogenic acute regulatory protein - transports cholesterol into the mitochondria once the side chain has been cleaved off
changing pregnenlolone into other steroids
2 types of enzymes involved
- cytochrome P450s (CYPs) - redox changes
- hydroxysteroid dehydrogenase HSDs = interconversons
how to make testosterone
17bHSD turns androstendone to testosterone
hot to make progesterone
Sb-HSD turns pregnenolone not progesterone
adrenal cortex produces
androstenedione, cortisol and aldosterone
androstenedione - requires CYP17a1 and 3b-HSD
cortisol - requires CYP21 and CYP11b1
aldosterone - requires CYP11b2 (aldosterone synthase)
testes produced
testosterone - 17b-HSD to convert androstenedione to testosterone
ova produce
progesterone - 3b-HSD converts pregnenolone into progesterone
oestrogen - requires CYP19a1 converts testosterone into oestradiol
StAR
steroidogenic acute regulatory protein
stimulates steroid production (rate limiting transport step)
found in all tissues that can produce steroids
transports cholesterol molecules into the mitochondria
regulated by cAMP
P450scc
cholesterol side chain cleavage
rate limiting catalytic step
regulated by cAMP
receptors for trophic hormones
activate cyclic AMP to activate StAR and P450scc
corticosteroids
mineralocorticoids - cortex hormones regulating minerals
glucocorticoids - cortex hormones that regulate glucose
sex hormones
what produces corticosteroids
adrenal glands - adrenal cortex (outer)
zona fasciculata produces
cortisol
zona glomerulosa
produces aldosterone because it has aldosterone synthase
zona reticularis produces
androstenedione
mineralocorticoids
produced by the zone glomerulosa of the adrenal cortex
secretion is mediated by primary angiotensin 2, and increase in local potassium
dominant for of mineralocorticoids
aldosterone (although some others also have mineralocorticoid function)
mineralocorticoids binds
MC - mineralocorticoids receptor in the cytoplasm
expressed in kidney, distal colon, sweat glands
activates signal transduction via gene transcription and heat shock proteins
aldosterone action in kidney
binds MC receptor to stimulate activity and expression of sodium channels and Na/K ATPase
increases blood pressure and blood volume
glucocorticoids
produce in the zona vessiculata of the adrenal cortex
regulated by ACTH (corticotrophin releasing hormone)
dominent form of glucocorticoids
cortisol
glucocorticoids bind
GR - glucocorticoid receptor
ubiquitous - in almost every cell
a receptor transcription factor to activate gene transcription
also represses the function of NK-kappaB and AP-1
what do glucocorticoids do
helps the body deal with stressful situations
- trauma, surgery, exercise, anxiety, depression, crowding, fasting, hypoglycaemia, fever, infection
regulated cardiovascular, metabolic and immune system function
keeps blood glucose high
breaks down protein for fuel source
in large quantitiess of glucocorticoids
depresses immune and inflammatory response
also redirects circulating lymphocytes to lymphoid/peripheral tissues
glucocorticoids on CHO metabolism
elevates blood glucose
- stimulate gluconeogenesis (mobilises AAs, increase conversion enzymes)
decrease cellular glucose uptake (mostly by muscle and adipose tissue)
glucocorticoids on lipid metabolism
elevates blood fat
mobilises FAs from adipose tissue
also stimulates beta oxidation for energy
glucocorticoids on protein metabolism
elevates blood [protein, AA]
mobilises AA from non hepatic tissues - enhances liver protein synthesis
anti inflammatory processes of glucocorticoids
inhibits cytokine release
block early stage inflammatory inception
increases healing of inflammation
surpasses cellular immune response, stabilises lysosomes, reduces vessel permeability
ACTH
adrenocorticotrophic hormone
acts on adrenal cortex
ACTH stimulate secretion af adrenal glucocorticoids
binds cell surface melanocortin type 2 receptors MC2R
ACTH binds melanocortin type 2 receptors
activate cAMP
MC2R most abundant in
zona fasciculata
ACTH regulates
steroid hormone secretion
stimulates lipoprotein uptake into cortical cells (increase cholesterol) plus mitochondria ox-phos genes (steroid synthesis requires lottos energy)
activates StAR and P450scc
stimulates transcription of the steroidogenic enzyme genes
ACTH
produced from POMC
pre-pro-opiomelanocortin
concurrently produces endorphin, lipotrophin and melanocyte stimulating hormone
b-endorphin binds opiate receptor
y-lipotropin stimulates lipolysis
a/b/y-MSH stimulates melanocytes and can darken skin
stimulation of ACTH release
CRH and ADH (hypothalamus)
stress
hypoglycaemia
circadian pattern of release
highest levels early AM
sleep-wake cycle
short term stress response
adrenaline and noradrenaline
increase blood glucose, increase blood pressure, increase breathing rate, increase metabolic rate, change in blood flow patterns
long-term stress response
mineralocorticoids sodium ions and water by kidneys
increase blood volume and blood pressure
glucocorticoids conversion of proteins and fats to glucose and immune system suppressed
Addisons disease
adrenal insufficiency
not enough cortisol or aldosterone
low blood pressure
low blood glucose
patients lack cortisol so there is no negative feedback fro ACTH
overproduction of ACTH
skin colour darkens (overproduction of melanocyte stimulating hormone)
Cushing’s syndrome
too much cortisol
may be because of too much CRH (hypothalamus tumour) or too much ACTH (anterior pituitary tumour)
rapid weight gain
central obesity
hypertension, muscle wasting, poor wound healing
hypercholesterolaemia, diabetes melllitus
sex hormones synthesised in
synthesised in the zona reticularis
DHEA (dehydroepiandrosterone) and androstenedione
converted in peripheral tissues to testosterone, oestrogen
testosterone is secreted by
leydig cells in the testis in response to LH
DHT
testosterone is converted to dihydrotestosterone by 5-alpha reductase which is only present in some target cells
amplifies action of testosterone in some target tissues
DHT-R complexes required for development of male external genitalia
testosterone feedback control
systemic testosterone powerfully inhibits GnRH and LH secretion
sertoli barrier
blood testes barrier
sertoli cells create locally high concentration of testosterone keeping it trapped in the testes to drive sperm production
concentrated testosterone without negative feedback
IV testosterone
does not arise testes androgen level
exerts negative feedback and stops production of testosterone
oestrogen potency
beta-oestradiol>oestrone>oestriol
oestrogen produced by
granulosa cells (also corpus luteum)
require aromatase activity
regulated by LH and FSH (via cAMP)
progesterone
corpus luteum (tiny amount from follicular theca cells) regulated by LH (via cAMP)
2 cells producing oestrogen
theca cells and granuloma cells
oestrogen from granuloma cells
release oestrogen but can’t make them from scratch themselves - must be supplied with androgens which may come from the adrenal cortex or from nearly theca cells
granuloma cells are responsive to
LH and FSH
process of making oestrogens
cholesterol - pregnenolone - progesterone - androgens - oestrogen’s
FSH catalises in the production of oestrogen
catalyses production of aromatase which converted androgens to oestrogen
theca cells are responsive to
LH
LH catalyses
cholesterol > pregnenolone
effects of oestrogen
- facilitate growth of ovarian follicles and uterine tube motility
cyclical changes in endometrium
increases blood flow and smooth muscle contractility of uterus
oestrogen-dominatedd uterus is more sensitive to oxytocin
increases breast duct growth
effects of progesterone
uterus - progestational changes in endometrium, cervix and vagina
antioestrogenic effects - prevents uterine contraction
breast - stimulates lobule and alveoli development, supports lactation
brain- stimulates thermogenesis and respiration
