Endo Exam 4: Glucocorticoids

Adrenal gland development: ___ origin. Contains ___ secreting cortex cells.

Mesodermal, steroid

Adrenal gland development: ___ cells of ___ origin. Contains ___ secreting tissue.

Neural, ectodermal, catecholamine

Adrenal gland development: in higher vertebrates ___ cells give rise to adrenal cortex

Mesenchymal cells

The adrenal medulla originates from ___

The neural crest. 

Zones of the adrenal cortex: zona glomerulosa generate ___

Aldonsterone (mineralcorticoid)

Zones of the adrenal cortex: zona fasiculata secrete ___

Glucocorticoids (cortisol)

Zones of the adrenal cortex: zona reticularis secretes ___

Sex steroid precursors (androgens, DHEA)

The type of steroid homronal produced by a particular adrenal cortex cell is dictated by ___

THe types of steroidogenic enzymes present at the cell

The zona glomerulosa lacks ___ (enzyme) and therefore makes ___, an aldosterone precursor

17 alpha hydroxylase, corticosterone

The glomerlosa cells DO contain the enzyme ___, which converts ___ to ___. 

Aldosterone synthase, corticosterone, aldosterone

Glucocorticoids promote ___ and antagonize ___ action to main plasma ___ levels and liver ___. They work with ___ to prevent basal plasma glucose levels from falling too low between meals.

Gluconeogenesis, insulin, glucose, glycogen, glucagon

___ is the principal glucocoritcoid but has some ___ activity at ___ doses

Cortisol, mineralocorticoid, high

___is the princial minderalcorticoid but has some ___ activity at ___ doses

Aldosterone, glucocorticoid, high

The stress system relies on two key hormone: ___ and ___ to increase available blood ___. ___ works short term, ___ has large momentuym and works long term. 

Adrenaline, cortisol, glucose, adrenaline, cortisol

___act slowly on the cell ___, changing patterns of ___, and leading to increased ___ and ___ breakdown, and increased ___.

Glucocorticoids, nucleus, gene expression, protein and lipid, gluconeogensis

Glucocorticoids have an overall anti-___, diabetogenic effect and have some ___ activity at ___ doses, promoting ___ retention and ___ loss.

Insulin, mineralcorticoid, high, sodium, potassium

___is a hypothalamic neurosecretory cell secretion, stimulating the relase of ___ from the ___.

Corticotropin-releasing hormone (CRH), adrenocorticotrophic hormone (ACTH), anterior pituitary

Cortisol release: ___ from hypothalamus stimulates ___ from the pituitary. ___ induces ___ synthesis and secretion. ___ exhibits ___ feedback on its own release at multiple levels. 

CRH, ACTH, ACTH, glucocorticoid (cortisol), cortisol, negative

Cortisol release: ACTH binds a ___ and activates ___ and ___ via ___. ___ is the effector for ACTH.

GPCR, cAMP, PKA, adenylate cyclase, cAMP

ACTH effects: effect of ACTH binding includes conversion of ___ into ___, ___ activity, and ___ expression. Increases ___ and ___ (rate limiting step of steroid adrenal production) result in ___ production and release.

Acetyl CoA, cholesterol, cholesterol ester hydrolase, StAR, free cholesterol, StAR, cortisol

Cholesterol homeostasis: acute ACTH stimulation- more ___ and ___ are converted to ___. ___ expression increases and more ___ are produced.

cholesterol esters, acetyl CoA, cholesterol, StAR, steroids

Cholesterol homeostasis: prolonged ACTH stimulation- not enough ___ or endogenous ___. ___ receptors increase to provide more extracellular sources of ___.

Esterfied cholesterol, cholesterol, LDL, cholesterol

Cortisol synthesis: 1.) start with ___ and convert to ___. 2.) Add ___ at carbon ___ to make ___. 3.) Add ___ to carbon ___ to make ___. 4.) Add ___ at carbon ___ to make ___. 

Cholesterol, pregnenolone, OH, 17, 17-OH-progesterone, OH, 21, 11-deoxycortisol, OH, 11, cortisol

Cortisol circulation: in plasma, the majority of cortisol circulates bound to ___. Binding to ___ is reversible and ___ cortisol is though to be the active form. 

Corticosteroid-binding globulin (CBG), CBG, free

Glucocorticoid receptors (GRs):___ induced transcription factors that stimulate ___, most often ___. GRs ___ and bind ___ in the enhancers of target genes. 

Ligand, gene expression, enzymes, dimerize, glucocorticoid response elements (GREs)

Cortisol effects: ___ increase the bodies tolerance to ___. They increase ___ function, preparing internal organs to deal with ___.

Glucocorticoids have ___ and ___ effects and reduce the ability to fight ___. ___, ___, and ___ are their most serious long-term side effecrs. 

Glucocorticoids, stress, sympathetic nervous system, stress.

immunosuppressive, anti-inflammatory, infections, osteoporosis, diabetes, muscle wasting

Effect of cortisol on glucose: Cortisol stimulates numerous process involved in increases and maintaining ___ levels. Cortisol counteracts ___ by increasing ___ and promotes breakdown of ___ and ___, mobiliazation of ___ and ___. 

Prolonged cortisol secreted causes ___. 

blood glucose, insulin, gluconeogenesis, protein, fat, amino acids, ketone bodies, hyperglycemia.

Cortisol effect overview:

-Corisol stimulates release of ___ from muscle. These are taken up by the ___  and converted to___.

-Increased circulating concentration of ___ stimulates ___ release. Cortisol inhibits ___stimulated uptake of ___ in muscle via ___.

-Cortisol has ___ effects on lipids

Amino acids, liver, glucose

Glucose, insulin, insulin, glucose, GLUT4

Lipolytic

Cortisol effects on muscle:

In the presense of cortisol, muscle ___ breaks down and ___ are realsed into circulation

Cortisol raises the ___ in the ___ by inhibiting ___ formation, decreasing ___ uptake by muscle and inhibiting ___ synthesis. 

The ___ utilizes these ___ to synthesize ___.

Cortisol conserves ___ by inihbiting ___ uptake in muscle

Protein, amino acids

Free amino acids, serum, collagen, amino acid, protein

Liver, amino acids, glucose

Glucose, glucose

Cortisol effects on adipose:

Coritol conserves ___ by inhibiting ___ uptake in adipose tissue

Glucose, glucose

Effect of cortisol on the liver:

There is an increase ___ breakdown in the liver. This leads to increased circulating ___ in the blood by increasing ___. 

Cortisol has ___ direct effect on insulin binding or signal transduction but counteracts the ___ of insulin, further aggravating the ___.

Glycogen, glucose, gluconeogenesis
No, effects, diabetic hyperglycemia

Cortisol decreases available immune response cells:

Activation of ___ branch of the immune response leads to ___/___ based inflammation.

Cortisol can weaken the activity of the immune system by decreasing ___ and ___ secretion. ___ proliferation and ___ differentiation both decrease. As a result the immune system shifts away from ___ and toward ___.

TH1, T cell, macrophage

IL-2, interferon-gamma, T cell, macrophage, TH1, TH2

Cortisol reduces inflammation:

Cortisol reduces ___ histamine secretion and stabilizes ___ membranes. The stabilization prevents their ___, preventing secretion of___.

Mast cells release ___ which acts on nearby ___. The ___ widen and become more ___. Fluid and phagocytic cells enter the tissue. 

Mast cell, macrophage lysosomal, rupture, inflammatory enzymes/chemical signals

Histamine, capillaries, capillaries, permeable

Effects of cortisol on bone:

Loss of bone ___. It lowers ___ formation, favoring developmet of ___ long term. 

Matrix, bone, osteoporosis

Effects of cortisol on kidney:

In addition to binding to the GR, because of its molecular similarity to ___, it can also bind to the ___ receptor. 

Cortisol and ___ have ___ affinity for the ___ receptor. 

Circulating concentration of coritsol are 100 times ___ than ___, but does not normally interact with the ___ receptor becasue cortisol is rapidly metabolised to inactive cortisone via ___.

___ in mineralcorticoid target tissues prevents overstimulation by ___ and allows selective mineralcoricoid action. This enzyme catalyzes ___ of glucocortioids to 11-dehydrometabolites. 

Aldosterone, mineralcorticoid

Aldosterone equal

Higher, aldosterone, aldosterone, 11B-OHSD type II

11B-OHSD, glucocorticoids, deactivation

Liquorice poisoning:

___acid in licorice inhibits ___, increasing ___ cortisol levels.

Cortisol accumlates and innaprropriately actives the ___ receptor and can mimic excess ___.

Glycyrrhetinic, 11B-OHSD

Mineralcorticoid, mineralcorticoids

Cushing’s:

Excess ___.

Symptoms:

• Osteoporosis due to ___

• Cardiac hypertrophy (mimic ___ effects)

• Buffalo hump (indirect fat deposition due to increased ___)

• Adrenal tumor/hyperplasia (ultimate cause)

• Muscle weakness due to ___

• Skin uclers due to ___

Cortisol

-protein degradation

-Aldosterone

-Insulin

-Proteolysis

-Decreased immune response