31. Hormones

Page created on March 14, 2018. Last updated on December 18, 2024 at 16:55

Learning objectives

• Which are the most important peptide hormones in biochemistry?
• Describe the structure of peptide hormones
• What are catecholamines, and where are they synthesised?
• Describe the synthesis of catecholamines
• What are eicosanoids?
• How are eicosanoids synthesised?
• Which drugs act on eicosanoid synthesis?
• What are steroid hormones?
• Describe the synthesis of steroid hormones
• Describe the receptors steroid hormones act on
• What is the function of vitamin D, and what receptor does it act on?
• What is the function of vitamin A, and what receptor does it act on?
• What is the function of thyroid hormones, and what receptors do they act on?

Hormones

Hormones are signal molecules produced by the body. The job of the hormone is to “transmit” the signal of this stimulus to other cells in the body, which allows many cells to act in a coordinated fashion.

We can classify hormones according to which cells they act on, generally speaking:

• Endocrine hormones are released into the bloodstream by the endocrine cells
  • Endocrine hormones travel with the blood and can therefore act on cells throughout the whole body
  • Most important hormones are endocrine
• Paracrine hormones are produced by endocrine cells, and they will reach neighbouring cells by diffusion
  • Paracrine hormones are not released into the bloodstream
  • They only act on cells very close to the endocrine cells
• Autocrine hormones are produced by endocrine cells and act on the same endocrine cell
  • These are not super-important for us right now

We can also classify hormones according to their structure:

• Peptide hormones are peptide chains made up of many amino acid
• Amine hormones are derived from a single amino acid
• Steroid hormones have a special steroid structure

Most hormones are synthesised ahead of time, so that they’re ready to be released when needed. This is because most hormones take some time to be synthesised. Eicosanoids are an exception.

Hormone receptors

Hormones act on target cells by binding to a certain protein on or in the target cell. These proteins are called receptors. Each hormone has a unique receptor (with a few exceptions). After the hormone has bound to its receptor on the target cell, it will trigger a cascade of intracellular processes which ultimately change the behaviour of the target cell, which is the whole point of hormones.

Most hormone receptors are located on the surface of the cells, but some hormone receptors are located inside the cells or even inside the nuclei. The former are called cell surface receptors of plasma membrane receptors, while the latter two are called intracellular receptors.

More about hormone receptors and their pathways in topic 32.

Peptide hormones

• Insulin
• Glucagon
• Anterior pituitary hormones
  • Growth hormone (GH)
  • Thyroid-stimulating hormone (TSH)
  • Adrenocorticotropic hormone (ACTH)
  • Follicle-stimulating hormone (FSH)
  • Luteinizing hormone (LH)
  • Prolactin
• Posterior pituitary hormones
  • Oxytocin
  • Vasopressin/Anti-diuretic hormone (ADH)
• Hypothalamic hormones
  • Corticotrophin-releasing hormone (CRH)
  • Dopamine
  • Growth hormone-releasing hormone (GHRH)
  • Somatostatin
  • Gonadotrophin-releasing hormone (GnRH)
  • Thyrotrophin-releasing hormone (TRH)

Peptide hormones are simple peptide chains with very different length; they can be anything from 3 – 200 amino acids long. Peptide hormones can be very similar to one another, but still have very different effects. Oxytocin and vasopressin, for example, differ only by two amino acids, but have very different effects. All hormones synthesized from the pituitary and hypothalamus are peptide hormones.

These hormones are synthesised by proteolytically cleaving hormone precursors. We’ll see an example of this in the insulin topic.

They bind to cell surface receptors.

Catecholamines

• Dopamine
• Epinephrine/adrenaline
• Norepinephrine/noradrenaline

Catecholamines are synthesized in the brain and in the medulla of the adrenal glands. They are amine hormones.

Norepinephrine and epinephrine bind to so-called α-adrenergic and β-adrenergic receptors on the cell surface. These hormones are released in periods of stress, and they increase the heart rate, blood pressure, and metabolism.

Synthesis

All catecholamines are synthesised from tyrosine. The pathway goes like this:

Tyrosine -> L-DOPA -> Dopamine -> Norepinephrine -> Epinephrine

The conversion of dopamine to norepinephrine requires vitamin C (ascorbate). Other cofactors involved in this synthesis are adoMet, THB, and PLP.

Eicosanoids

• Prostanoids
  • Prostaglandins
  • Thromboxanes
• Leukotrienes

Eicosanoids are hormones that are derived from arachidonic acid, a polyunsaturated fatty acid. They act on neighbouring cells, or in other words they’re paracrine hormones. They bind to cell surface receptors and intracellular receptors.

Synthesis

Membrane phospholipids are converted into arachidonic acid by the enzyme phospholipase A2.

A group of enzymes called cyclooxygenases (COX) can convert arachidonic acid to prostaglandins and thromboxanes. Prostaglandins and thromboxanes are pro-inflammatory. Lipoxygenase converts arachidonic acid to leukotrienes.

Characteristics

Eicosanoids are not stored in cells; they’re rather synthesised from phospholipids when needed. This process takes nothing more than a few seconds.

Clinical relevance

So-called non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin and ibuprofen inhibit the COX enzymes, thereby preventing formation of prostaglandins and thromboxanes, reducing inflammation.

Corticosteroids, discussed below, inhibit phospholipase A2, thereby preventing arachidonic acid release, reducing inflammation.

Steroid hormones

• Sex hormones
  • Progesterone
  • Testosterone
  • Oestrogen
• Mineralocorticoids
  • Aldosterone
• Glucocorticoids
  • Cortisol

Steroid hormones have the steroid structure which was described in topic 8.

Cortisol is a chronic stress hormone. It stimulates gluconeogenesis, suppresses the immune system, increases insulin resistance, and increases the blood pressure.

Aldosterone regulates the renal balance of sodium, water and potassium.

The sex hormones affect sexual development, sexual behaviour, muscle growth, and other stuff.

Synthesis

Different steroid hormones are synthesized in different cells of the body, but all are synthesized in mitochondria from cholesterol (which is synthesized in cytosol and ER). They’re all synthesised by the adrenal cortex. Testosterone is also synthesised in the testis, and oestrogen and progesteron are synthesised in the ovaries.

Receptors

These hormones don’t act on cell surface receptors. Instead, they freely diffuse across the cell membrane due to their lipophilicity and bind to intracellular receptors. The intracellular receptor of steroid hormones are so-called type I nuclear receptors.

Glucocorticoids act through the glucocorticoid receptor (GR), aldosterone acts through the mineralocorticoid receptor (MR), testosterone acts through the androgen receptor (AR), and oestrogens act through the oestrogen receptor (ER).

After binding to intracellular receptors these hormone, together with their receptors, act as transcription factors.

Clinical relevance

Drugs which have glucocorticoid functions are called corticosteroids, or often just steroids. These drugs are widely used in medicine as they’re powerful anti-inflammatory drugs.

Vitamin D derivatives

• Calcitriol

Calcitriol is the main vitamin D derivative hormone. It is a steroid-like hormone, and its synthesis is described in topic 8. The skin, kidney and liver are all involved in the synthesis of calcitriol.

Calcitriol is important in calcium homeostasis, the balance between Ca²⁺ in deposition and Ca²⁺ mobilization from bone.

Vitamin D derivatives bind to vitamin D receptor (VDR), a type of type II nuclear receptor.

Retinoids

• Retinoic acid

Retinoids are hormone derivatives of vitamin A, the most important of which is retinoid acid. It is synthesized in the liver from vitamin A.

Retinoids acts through type II nuclear receptors called retinoid acid receptors (RAR) and retinoid X receptors (RXR).

Retinoids are important in vision, regulating growth, survival and differentiation of cells.

Thyroid hormones

• Triiodothyronine (T3)
• Thyroxine (T4)

Thyroid hormones are produced in the thyroid gland. They’re synthesised from thyroglobulin (which is a derivative of tyrosine) and requires iodine.

They act through thyroid hormone receptor (TR), a type of type II nuclear receptors. These hormones stimulate energy metabolism in the liver and the muscle.

Summary

• Which are the most important peptide hormones in biochemistry?
  • Insulin and glucagon
• Describe the structure of peptide hormones
  • Peptide hormones are peptide chains 3 – 200 amino acids in length
• What are catecholamines, and where are they synthesised?
  • Dopamine, epinephrine, and norepinephrine are catecholamines
  • They’re synthesised in the brain and in the medulla of adrenal glands
  • These hormones are stress hormones
• Describe the synthesis of catecholamines
  • Tyrosine -> L-DOPA -> Dopamine -> Norepinephrine -> Epinephrine
  • The conversion of dopamine to norepinephrine requires vitamin C
• What are eicosanoids?
  • Eicosanoids are derivatives of arachidonic acid, a polyunsaturated fatty acid
• How are eicosanoids synthesised?
  • Arachidonic acid is cleaved from membrane phospholipids by phospholipase A2
  • Arachidonic is converted to thromboxanes and prostaglandins by COX or to leukotrienes by LOX
  • Eicosanoids are not stored, but rather synthesised when needed
• Which drugs act on eicosanoid synthesis?
  • NSAIDs like aspirin and ibuprofen inhibit COX
  • Corticosteroids inhibit phospholipase A2
• What are steroid hormones?
  • Steroid hormones are hormones with steroid structrue
• Describe the synthesis of steroid hormones
  • Cholesterol is synthesised in cytosol and ER
  • The hormone is synthesised from cholesterol in the mitochondria
  • All steroid hormones are synthesised by the adrenal cortex.
  • Testosterone is also synthesised in the testis
  • Oestrogen and progesteron are synthesised in the ovaries.
• Describe the receptors steroid hormones act on
  • Glucocorticoids act on glucocorticoid receptor (GR)
  • Mineralocorticoid act on mineralocorticoid receptor (MR)
  • Testosterone acts on androgen receptor (AR)
  • Oestrogens act on oestrogen receptor (ER)
  • All of these receptors are type I nuclear receptors
• What is the function of vitamin D, and what receptor does it act on?
  • Vitamin D is involved in calcium homeostasis
  • It acts on vitamin D receptor, a type II nuclear receptor
• What is the function of vitamin A, and what receptor does it act on?
  • Vitamin A is involved in differentiation, growth, and vision
  • It acts on retinoic acid receptors (RAR) and retinoid X receptors (RXR), both are type II nuclear receptors
• What is the function of thyroid hormones, and what receptors do they act on?
  • Thyroid hormones stimulate energy metabolism
  • They act in thyroid hormone receptor, a type of type II nuclear receptor