Adrenal gland and steroid hormones

Types of peptide hormones (6)

TRH

ADH

insulin

GH

FSH

TSH

hormones - amine derived from tyrosine/tryptophan

thyroxine

catecholamines - adrenaline, noradrenaline, dopamine

Lipid derived hormones

eicosanoids - prostaglandins, thromboxanes, leukotrienes

testosterone

cortisol

calcitrol

aldosterone

Embryological origin of the outer cortex of adrenal gland

developed from mesoderm (coelomic mesoderm)

• produce steroid hormones

• controlled by pituitary

Embryological origin or the inner medulla of the adrenal gland

derived from neural crest (neuroectoderm)

• consists of cells secreting catecholamines (chromaffin)

• under nervous control

Adrenals in the foetal cortex - wk 20

adrenals (mostly cortex) larger than kidney

• responsive to ACTH

• adrenal hormones involved with maturation of lung and other systems

• e.g. gut closure (IgG transport) under influence of corticosteroids

What does the neural crest cell form? (11)

• adrenal medulla

• ganglia - sensory, autonomic

• melanocytes

• Schwann cells

• meninges - pia, arachnoid

• pharyngeal arch cartilage

• odontoblasts

• parafollicular C cells

• aorticopulmonary system

• endocardial cushions

• facial skeleton

Blood supply of the adrenal gland

IVC, aorta, left renal artery

left renal vein

Adrenal cortex and medulla histology

Zona glomerulosa – mineralocorticoids, eg, aldosterone

• columnar/ovoid cells

Zona fasciculata -  glucocortocoids, eg, cortisol

• sinusoids between columns of cells

Zona reticularis  - gonadocorticoids, eg, androgens

• cells arranged in cords seperated by sinusoids

Medulla – adrenaline, noradrenaline (chromaffin cells)

• pale staining, cells arranged in groups - rich blood supply

Ultrastructure - steroid secreting cell from cortex

Cholesterol stored in lipid droplets until used

Ultrastructure - peptide secreting cell from medulla

Innervation of the adrenal medulla

Preganglionic fibres cause the suprarenal medulla to pour forth adrenalin

Vasomotor supply to suprarenal gland reaches it by postganglionic fibres

How is cholesterol turned into adrenal steroid hormones? (steroidogenesis)

1. cholesterol obtained from blood as LDL or synthesised from acetyl- CoA

2. rate limiting step: transport of cholesterol from outer to inner mitochondrial membrane

3. cleavage of cholesterol side chain → pregnenolone

4. pregnenolone converted to:

   • aldosterone (zona glomerulosa)

   • cortisol (zona fasciculata)

   • testosterone, oestrone, oestradiol, oestriol (zona reticulaire)

Mineralocorticoid pathway (zona glomerulosa)

1. pregnenolone

2. progesterone

3. 1,1 deoxycorticosterone

4. corticosterone

5. aldosterone

Glucocorticoid pathway (zona fasciulata)

1. pregnenolone

2. 17-a-hydroxypregnenolone

3. 17-a-hydroxyprogesterone

4. 11-deoxycortisol

5. cortisol

Sex hormone pathway (zona reticularis)

1. dehydroepiandrosterone

2. androstenedione

3. testosterone, oestrone, oestradiol, oestriol

What is the HPA axis and what does it consist of?

Hypothalamus-pituitary-adrenal axis

Includes:

• corticotropin-releasing hormone (CRH)

• adrenocorticotropic hormone (ACTH)

• cortisol

What stimulates aldosterone secretion and what does it do?

Secretion stimulated by raised [K+], Ang II, and ACTH

helps your body retain salt and water and get rid of potassium. This helps control blood pressure and fluid balance.

What happens when there is a stress stimuli? (steroid feedback)

1. Stress stimulus activates hypothalamus.

2. Hypothalamus releases CRH (Corticotropin-Releasing Hormone).

3. CRH stimulates the anterior pituitary to release ACTH (Adrenocorticotropic Hormone).

4. ACTH travels via the bloodstream to the adrenal glands, triggering the release of cortisol.

5. High cortisol levels provide negative feedback:

   • Suppress further release of CRH from the hypothalamus.

   • Suppress further release of ACTH from the anterior pituitary.

What is diurnal rhythm?

Biological clock, controlled by suprachiasmatic nucleus (SCN)

• e.g. cortisol levels peak in morning then decreases, low body temp in morning then increases

Where are steroid hormones synthesised and how are they transported?

Produced in endocrine, released by simple diffusion

Transported in the circulation bound to plasma proteins (carriers)

How do steroid hormones act at target cells?

1. Steroid hormones diffuse though cell membrane

2. Hormone binds to intracellular receptors in cell

3. Hormone-receptor complex becomes active and binds to DNA sequence

4. Gene expression is modulated

5. New proteins/biological effects

Actions of cortisol

• metabolic

  • muscle and adipose - catabolic

  • liver - stimulate gluconeogenesis and glycogen storage

  • overall - elevate plasma glucose levels

• anti inflammatory/ immunosuppressive effects

• role in adaptation to stress

What are the anti-inflammatory/immunosuppressive effects of cortisol? (5)

• stimulate production of lipocortin 1 (annexin1) - inhibits PLA₂ (generates arachidonic acid), precursor for prostanoids & leukotrienes

• Decrease number and activation of T-lymphocytes

• Decrease production of cytokines (interleukins, TNF-a that recruit other inflammatory cells)

• Stabilises lysosomes (reduces neutrophil bacterial killing processes)

• Decrease NO production (reduce vasodilation)

Anti-inflammatory examples of use of glucocorticoid analogues

• Asthma, COPD

• Ulcerative colitis, Crohn’s disease

• Rheumatoid arthritis

• Skin conditions, e.g. eczema, psoriasis

• Others, inc. rhinitis, conjunctivitis, local injections (joints/ soft tissue)….

• Dexamethasone in ARDS

immunosuppression/replacement therapy examples of use of glucocorticoid analogues

Immunosuppression - organ transplantation

Replacement - Addison’s disease