Adrenal Steroid Hormones

Question 1

What us the structure of a steroid?

Answer 1

They are all derived from cholesterol and they all have the same 4 ring structure with variable side groups.

Question 2

What are the production sites of steroids?

Answer 2

They are produced and released from a few types of ‘classic’ glands (and a few other sites).

1. Adrenal (=upon+kidney)
   aldosterone, glucocorticoids and a small amount of sex steroid hormones.
2. Gonad…testes and ovary produce ‘sex steroids’ androgens (T and DHT), estrogens, progestins (&some protein/peptides hormones)
3. Placenta and corpus luteum of pregnant women
4. Brain - produces small amount of steroids de novo… and converts T into E (via an enzymes aromatase)

*The female hormone E2 can cause some male behaviors.

Question 3

How are steroids transported?

Answer 3

Produced upon upstream signal -> activation of enzymes that converts cholesterol or inactive (or precursor) steroid -> diffuse out of cell.
Steroids are very hydrophobic (lipophilic), so they do not go into solution in plasma very well. As a result steroids often travel in blood, bound to carrier proteins (specific or nonspecific)

They may bind “nonspecifically” to albumin a very abundant plasma protein that:
1. binds various materials for transport
2. maintains plasma osmotic pressure, and
3. is made in the liver

In addition to facilitating transport, binding proteins can protect from degradation, therefore, increasing the half life of the steroid.

Question 4

How do steroids connect with receptors?

Answer 4

Steroid hormones will diffuse through the membrane and bind to receptors within target cells.

In some cases, the steroid/carrier protein complex will interact with the target cell membrane -> it will deliver the steroid to the ‘right’ type of cell (i.e. target tissue) (some take-in carrier protein-hormone complex)

Question 5

What is a cytosolic or nuclear receptor?

Answer 5

A hormone receptor complex binds DNA at specific sites -> leading to gene expression.

Question 6

What are steroid response elements (SREs)?

Answer 6

regions of promoter DNA sequence at which receptor-steroid complex binds (aided by response element binding proteins)

*Binding causes (and in some cases) inhibits gene expression

Question 7

What is the response time of steroid hormones?

Answer 7

Responses generally take longer than proteins and occur more in the time range of many minutes to hours. However, some steroids can act quickly through membrane bound receptors.

Question 8

What is steroid hormone action?

Answer 8

1. Most hydrophobic steroids are bound to plasma protein carriers. Only unbound hormones can diffuse into the target cell.
2. Steroid hormone receptors are typically in the cytoplasm or nucleus.
   2a. Some steroid hormones also bind to membrane receptors that use second messenger systems to create rapid cellular responses.
3. The receptor hormone complex binds to DNA and activates or represses one or more genes.
4. Activated genes create new mRNA that moves into the cytoplasm.
5. Translation produces new proteins for cell processes.

Question 9

What are the adrenal glands?

Answer 9

The are found attached to each kidney. The adrenals are comprised of two glands, the cortex and the medulla. The cortex surrounds the medulla, it also produces steroid hormones which are involved in blood ion and glucose regulation.

Question 10

What does the cortex produce?

Answer 10

It produces glucocorticoids and mineralcorticoids.

Question 11

What do glucocorticoids do?

Answer 11

They play a major role in the metabolism of carbohydrates, lipids and proteins.

Question 12

What does aldosterone do?

Answer 12

It is a mineralcorticoid that plays an important roles in the regulation of Na+ and K+ reabsorption and excretion by the kidney.

Question 13

How do the cortical hormone act?

Answer 13

All cortical hormones act via the pathway described for lipophilic hormones.

Question 14

How does AdrenoCorticoTropic Hormone (ACTH)?

Answer 14

It comes from the pituitary and stimulates the release of glucocorticoids from the adrenal cortex including cortisol, cortisone and corticosterone.

Question 15

How is is basal output regulated?

Answer 15

It is regulated by negative feedback of glucocorticoids on ACTH at the pituitary and on CRH at the hypothalamus.

Question 16

What is the circadian rhythm of glucocorticoids?

Answer 16

There is a daily peak of glucocorticoids is very important, this peak increases vascular tone and alertness it also mobilizes energy and has a priming effect on the immune system. (Essentially your morning dose of cortisol prepares you to face the potential challenges in your day)

Question 17

How does stress effect glucocorticoid levels?

Answer 17

It can drive additional pulses of glucocorticoids from the adrenal which drive sustained, elevate glucocorticoid levels, these produces the same physiological responses but with greater magnitude.

Question 18

What glucocorticoid produces the vast majority of activity in most mammals?

Answer 18

Cortisol.
About 10% of circulating cortisol is free, the remaining majoring circulates bound to plasma proteins, particularly corticosteroid-binding globulin (transcortin).
- There is a circadian rhythm of cortisol release with secretion being highest just before waking in the morning.

Question 19

What are physiological effects of glucocorticoids?

Answer 19

At the liver, glucocorticoids act to stimulate gluconeogenesis (synthesis of glucose form precursors other than carbohydrates) -> This newly synthesized glucose increases blood glucose levels and serves as energy for muscles and nervous tissue

• Mobilization of amino acids from extraheptic tissues: these serve as substrates for gluconeogenesis.
• Inhibition of glucose uptake in muscle and adipose tissue: A mechanism to conserve blood glucose.
• Stimulation of fat breakdown in adipose tissue: The fatty acids released by lipolysis are used for production of energy in tissues like muscle and the released glycerol provide another substrate for gluconeogenesis.
• The effects of GS on adipocytes will differ based on the location of fat stores. It will stimulate lipolysis in subcutaneous adipose tissue, whereas it stimulates differentiation and hypertrophy of adipocytes in visceral adipose tissue, such effects are consistent with the phenotype of patients with Cushing’s disease
• Increased cortisol levels can cause an increase in collagen degradation which results in disruption of the extracellular matrix in the dermis, resulting in stretch marks.

Question 20

How do glucocorticoids effect the immune system?

Answer 20

They inhibit the immune system and inhibit inflammation responses (cortisol is often used as an anti-inflammatory)

Not all actions on the immune system are inhibitory. It can increase the ability of the immune system to detect pathogens/injury and respond accordingly, and it facilitates resolution and repair, to restore balance.

In the context of chronic infection or disease, however the role of glucocorticoids changes, in order to prevent escalation and limit damage.