The Endocrine System

The endocrine system controls processes throughout the body - growth, reproduction, blood solute concentration, blood glucose and temperature - through the regulated production and secretion of hormones (chemical messengers). It consists of a group of ductless glands that release hormones directly into the blood, which carries them to every part of the body. Each hormone, however, acts only on target cells that carry its matching receptor.

Two further properties of hormones should be noted. First, a hormone does not act on the gland that produces it. Second, endocrine responses are slow to begin - the hormone must travel through the body, and in some cases must be synthesised before a response can occur - but they last far longer than a nervous response.

GLANDS AND THEIR HORMONES

FOUR CHEMICAL CLASSES OF HORMONE

Hormones are amino acid derivatives, peptides, proteins or steroids. The chemistry of a hormone determines where its receptor is located:

• Protein hormones (e.g. FSH, insulin) - bind specific receptors on the outside of the cell membrane. Binding causes a conformational change in the receptor, which signals through a cascade pathway (transduction) of messenger molecules to the nucleus, resulting in gene expression.
• Peptide hormones (e.g. TSH, growth hormone, oxytocin) - short chains of amino acids, made via transcription and translation. They cannot cross the membrane, so they also bind surface receptors and trigger a messenger cascade.
• Steroid hormones (e.g. testosterone, oestrogen, progesterone) - lipophilic (lipid-soluble), so they diffuse freely across the membrane and bind receptors in the cytoplasm or nucleus, directly controlling gene expression.
• Amino acid derivatives - often synthesised from tyrosine or tryptophan; they bind surface receptors and act in the same way as protein and peptide hormones.

Water-soluble hormones bind a surface receptor and signal inward through a messenger cascade; lipophilic steroid hormones pass through the membrane to a receptor inside the cell. Both routes end in gene expression.

BLOOD GLUCOSE: INSULIN AND GLUCAGON

Blood glucose that is too high or too low damages cells, tissues and organs, so it must be held within tolerance limits. Two hormones produced by specialised cells of the pancreas act as an antagonistic pair (their effects oppose each other) under negative feedback:

• Insulin - released by beta cells when high blood glucose is detected. It triggers cells to take up glucose from the blood, triggers liver cells to convert glucose into glycogen for storage, promotes glucose uptake by adipose tissue, and promotes cellular respiration (ATP production) so that cells break glucose down faster. Net effect: blood glucose falls.
• Glucagon - released by alpha cells when low blood glucose is detected. It stimulates glycogen breakdown in the liver, promotes the release of stored energy from adipose tissue, and can slow cellular respiration to spare glucose. Net effect: blood glucose rises.

Blood glucose control drawn in the same loop form as thermoregulation: a rise in glucose drives the insulin loop (top); a fall drives the glucagon loop (bottom). Each response is negative feedback (N) returning glucose to normal.

DIABETES MELLITUS

If insulin is missing or ineffective, blood glucose remains high. This condition is diabetes mellitus, a disease of hormonal imbalance. The two types have different causes:

TSH AND THYROXINE: SETTING THE METABOLIC RATE

The hypothalamus, pituitary and thyroid operate a negative feedback loop that links body temperature to metabolism:

1. Stimulus (S): body temperature falls below 37 °C.
2. The thermoregulatory centre of the hypothalamus (R1) detects the fall and stimulates the pituitary gland to release thyroid-stimulating hormone (TSH).
3. TSH travels in the blood (T) to the thyroid gland, where it is detected by a specific receptor on thyroid cells; a relay of messages to the nucleus results in the release of thyroxine.
4. Thyroxine raises the base-level metabolism of most body cells - any cell with thyroxine receptors (E) - producing more reactions, more ATP turnover and more heat (R2).
5. Once the body has returned to 37 °C the stimulus is removed, and negative feedback (N) inhibits the release of TSH and thyroxine.

In summary: fall in body temperature (S) → hypothalamus (R1) → TSH, then thyroxine (T) → body cells (E) → increased metabolic rate and heat (R2) → negative feedback (N).

Cold → hypothalamus → TSH → thyroxine → heat. Rising thyroxine and temperature switch the loop off again (dashed arrow).

ADH AND OSMOREGULATION

Osmoregulation is the maintenance of the proper solute concentrations in all of the body's fluids - blood plasma, tissue fluid and the cytoplasm inside cells - as water constantly enters and leaves through digestion, excretion and sweating. The controlling hormone is antidiuretic hormone (ADH), which is synthesised in the hypothalamus and stored in the pituitary gland.

• Blood too concentrated (high osmolarity, low blood volume) → the osmoregulatory centre in the hypothalamus detects the change → the pituitary releases more ADH → ADH is recognised by receptors on the cells lining the kidney tubules and collecting ducts → these cells insert more aquaporins (water-channel proteins), increasing their permeability → water is reabsorbed into the blood → urine volume decreases and blood volume increases.
• Blood too dilute (low osmolarity, high blood volume) → the hypothalamus inhibits ADH release → aquaporins are reduced and the tubules are no longer permeable → water remains in the filtrate → a large volume of dilute urine is produced, and blood volume falls.

Because blood pressure is set largely by blood volume, the two move together: more ADH → more water reabsorbed → blood volume and blood pressure rise (and solute concentration falls - negative feedback). Everyday factors that alter the water–solute balance include the amount of water drunk, salty foods, heavy exercise and sweating, and blood loss from bleeding.

The ADH loop: concentrated blood → more ADH → aquaporins reabsorb water → blood volume and pressure rise → stimulus removed.