Dr. A

undergo transcription and translation, shuttled to rough er and golgi apparatus for post translational processing. Can be stored in secretory granules and accumulate before being released by exocytosis. Hydrophilic, free in solution, but must undergo transport to cross capillary walls and cell membranes.

produced by editing of a steroid backbone by an enzyme protein, cholesterol based. little to no storage for steroids, immedietly released from cell. Hydrophobic, so often need carrier protein in solution, but able to freely cross target cell membrane and capillary walls.

The cell producing the hormone is the target of the hormone. Cell is self regulating.

Cells near the producing cell is the target of the hormone.

Hormone travels through blood to distant target cell.

Pharyngeal epithelial cells, needs connection to hypothalamus provided by portal system

the embryonic brain, outgrowth of the hypothalamus that stays directly connected to it.

nuclei

antidiuretic hormone, ADH, vasopressin

oxytocin

supraoptic and paraventricular neurones

median eminence

blood vessel smooth muscle

contract blood vessels, which increase blood pressure

kidney tubule cells

water recovery

It is produced in the hypothalamus, delivered directly to the posterior pituitary through the supraoptic nuclei, and then delivered systemically. It acts on V1 and V2 receptors to contract blood vessels and increase water reabsorption respectively. Small protein based hormone.

Produced in the hypothalamus, delivered directly to the posterior pituitary through the paraventricular nuclei, and then delivered systemically. It increases uterine muscle contration to promote labor late in preganancy, and causes contraction of myoepithelial cells in the breast to promote milk secrection. Small protein based hormone, also produced by placenta late in pregnancy.

It is produced in the hypothalamus, and then released to the portal system by the median eminence. It then reaches the anterior pituitary and stimulates gonadatrope cells, which then causes production of LH and FSH, the gonadatrope hormones.

In a pulsatile fashion, with amount released going up an down over time. Released for about 15 minutes every 90 minutes.

receptor attenuation, where the GnRH receptors become less responsive to the same amount of hormone.

If there are high constant levels of GnRH, then the receptors will become attenuated and decrease their production of FSH and LH. This will cause a downstream effect of decreasing testosterone production. Testosterone can increase the growth of cancerous cells, so this pathway is used to decrease testosterone levels. However, when therapy is initiated there is a time before attenuation occurs, where the patient will have high levels of FSH and LH, and therefore high levels of testosterone.

Females: ovarian follicle growth and synthesis of estrogen
Males: sperm development by supporting sertoli cell function

Sertoli cells support sperm development and are located in the testes, however they are NOT the precursor to sperm cells.

Females: ovulation and synthesis of progesterone (and continued estrogen) within corpus luteum
Males: testosterone synthesis in Leydig cells

FSH and LH share the same alpha chain, however their beta chains are different and determine whether they bind of FSH receptors or LH receptors.

Produced by the median eminence of the hypothalamus, it is released to the portal system and then delivered to the anterior pituitary. This causes the synthesis and release of growth hormone, also known as somatotropin

Produced by the median eminence of the hypothalamus, it is released to the portal system and then delivered to the anterior pituitary. This causes inhibition of the synthesis and release of growth hormone, also known as somatotropin. GHIH is also known as somatostatin, or somatotropin release inhibiting factor, SRIF

A synthetic analogue of GHIH, so it has a better half life and is more stable.

GH binds to a JAK receptor on the cell. These receptors phosphorylate themselves an another protein. The other protein is STAT, signal transducer and activator of transcription. So GH binds to the JAK receptor, which phosphorylates itself and the STAT protein. This STAT protein then goes into the nucleus and activates the IGF1 gene, insulin like growth factor 1. This is also known as somatomedins, which are then released by the liver to promote growth.

It becomes a producer of somatomedins

1. It has anabolic effects, increasing metabolism, growth, and mass.
2. Lypolytic effects, breakdown of lipids and fatty acids, helps to meet energy needs for anabolic effects, reduces breakdown of proteins for energy use, protein sparing.

3. Under higher than normal levels of IGF-1 (somatotropin) or GH, you start to see diabetogenic effects. This is a 2 stage response. More glucose will be removed from the blood, causing glycogen deposition in liver and muscles and reducing blood sugar. However, this is a temporary initial response, after some more time and longer term, the second response will occur. This secondary response causes less glucose to be transported into the cells, and results in an increased blood sugar level that is NOT responsive to insulin.

Giantism

acromegaly, an increase in soft tissue mass and organ size
cariomegaly, specifically an increase in heart size
causes an increase in bone thickness, not length.

Produced in the hypothalamus, delivered to the anterior pituitary through the median eminence and portal system, in order to stimulate the release of adrenocorticotropic hormone, ACTH, corticotropin from corticotrope cells. ACTH then acts downstream to activate adrenals in order to produce corticosteroids.

Once the corticotrope cells in the anterior pituitary are stimulated by CRH, they produce pro-opiomelanocortin, POMC, which is cleaved to produce ACTH. There are other derivatives of POMC, which means that as ACTH production is increased, so is the production of these other derivatives.

ACTH stimulates the production of many different corticosteroids in the adrenal glands. Usually a patient will be deficient in one or more of these, but not all. If that patient is treated with ACTH, they will have increased levels of the corticosteroid they were not deficient in. So patients are usually treated with the specific corticosteroid they are deficient in.

when there is sufficient levels of ACTH in the blood, but the adrenal gland is still not producing the correct amount of corticosteroids. This is an issue with the adrenal gland itself.

When there is not sufficient levels of ACTH in the blood, but the adrenal gland does work properly, so if ACTH levels were increased there wouldn't be an issue. This is an issue with the anterior pituitary not producing enough ACTH, or the hypothalamus not producing enough CRH.

Externally, it can be slowed by the breakdown of ACTH. If less ACTH is produced, than the existing hormones will be broken down and stimulation will slow. Additionally, within the cell, there can be an internal breakdown of cAMP by PDE 11, phospodiesterace 11.

corticosteroid binding globulin (CBG) and albumin

albumin is much more common than CBG, but has much lower affinity for steroids.

CBG has a higher affinity for cortisol than aldosterone, so as cortisol levels rise they displace aldosterone from the protein. This causes it to enter cells at a higher rate and cause more aldosterone related effects.

Mineralcorticoids, gluccorticoids, and sex steroids

aldosterone

it causes the reabsorption of Na+, which increases the recovery of water. This increases blood volume, therefore blood pressure.

Since it is lipid based, it easily diffuses across the cell membrane. It binds to the cytoplasmic aldosterone receptor, which causes a conformational change and release of heat shock proteins (HSPs). Aldosterone and the receptor then relocate to the nucleus, and bind to DNA as a transcription factor. This causes an increased production of proteins that will cause reabsorption of Na+.

Most commonly would be the mineralcorticoids such as aldosterone. However, some glucocorticoids can also activate the receptor, such as cortisol (hyrdocortisone), which has high affinity for the McR. A more processed form of hydrocortisone, cortisone, has much lower affinity for the McR.

kidney tubule cells have an enzyme that converts hydrocortisone to cortisone, which then has a much lower affinity for McR.

cortisol, or hydrocortisone

regulated metabolism of multiple biopolymers.

increases rate of glucogenesis, the production of carbohydrates from non carbohydrates such as proteins. This increases blood sugar levels.

increases rate of protein breakdown in order to fuel glucogensesis. Protein synthesis also decreases.

increases oxidation of fatty acids as an energy source.

Adrenal overactivity of adrenal gland due to local tumor, which leads to excess corticosteroid production.

over stimulation of adrenal gland by an overproduction of ACTH, through a tumor in the anterior pituitary corticotrope cells.

cushings disease like symptoms caused by long term use of corticosteroids used for immunosuppression, more common than gland diseases.

it is a glucocorticoid receptor GcR antagonist, and has 18x more affinity than cortisol, with no release of heat shock proteins. However, it is also a progesterone receptor antagonist, which can cause side effects. Additionally, this will reduce the negative feedback response of corticosteroids, leading to an increased production of ACTH. While the glucocorticoid levels will remain ineffective due to the antagonism provided by mifepristone, there may be side effects from increased levels of other corticosteroids.

it blocks many early steps in the steroid synthesis pathway, preventing cholesterol from being converted into steroids. This will reduce the levels of many steroids in the body.

similarly to ketoconzaole, this works to block steps in the steroid synthesis pathway. However, this drug blocks the last step in the cortisol production pathway, 11-B oxidation, rather than early steps for all steroids, so it much more selectively inhibits glucocorticoids.

It binds to McR an agonizes it, increasing Na+ uptake and water retention, increasing blood pressure. There is some crossover effect that will agonize the glucorticoid receptor, so may change blood sugar levels.

It binds to McR and antagonizes it, causing no conformation change or release of HSPs. Less Na+ uptake, less water retention, diuretic effect, decreased blood pressure. However, also potentially causes an androgen receptor antagonistic effect, which can cause side effects.

Immediate: They enter cells that contain leaky lysosomes, which are causing inflammation, and work to stabilize the membranes to prevent their leakage.

Delayed: Part 1: binds to glucocorticoid receptors to shed heat shock protein and transport into the nucleus. In the nucelus, they promote the transcription of genes that are associated with wound and tissue repair.
Part 2: They prevent Jun and Fos from combining into AP-1, which would drive the transcription of collagenases which lead to the breakdown of connective tissue.

It is used topically to reduce inflammation, but not used systematically because it is not selective to the GcR and will activate the McR at too high of a level, leading to an increase in blood pressure. Short half life.

Used for systemic anti-inflammatory and immunosuppressive effects, does cause some activation of McR but relatively less than hydrocortisone. Intermediate acting.

Used for systemic inflammation or septic shock, have very little McR activation and strong activation of GcR. Long half life.