Hormonal Regulation of Growth

Now we're onto our last topic for PHYL3003: Nutrients for Growth and Activity!

Outline how the endocrine system regulates growth and development

The main hormones involved in growth are growth hormone (GH) and insulin-like growth factors, like IGF-1. GH is stimulated by GHRH, thyroid hormones and sex steroids and inhibited by somatostatin. GH can directly stimulate growth, or stimulate IGF-1. IGF-1, which can also be stimulated by insulin, can also stimulate growth.

Describe the physiological functions of growth-regulating hormones

In this section, I'm going to focus on GH, since there's a section on IGFs coming up next. GH is the most abundant hormone in the anterior pituitary, and its secretion is stimulated by GHRH (growth-hormone releasing hormone), which in turn can be stimulated by stress, exercise and deep sleep. GH release is pulsatile and follows a circadian rhythm, peaking in the first few hours of sleep. GH is controlled by a negative feedback loop- high levels of GH inhibit further GHRH secretion.

GH has a wide variety of actions. It can increase amino acid transport and protein synthesis, stimulating growth. It can also increase lipolysis and reduce glucose transport and metabolism, which is thought to ensure that there is enough glucose to supply the brain. GH can also increase fibroblast differentiation and increase the production of IGF in the liver and fibroblasts. Time to talk about IGF in some more detail...

Describe the function and regulation of Insulin-like growth factors (IGFs)

IGF can be produced by various tissues of the body. The liver can produce and secrete it, whereas other tissues (such as skeletal muscle, heart and bone) make tissue-specific IGF-1 which they cannot secrete into the circulation (though they do have autocrine and paracrine effects). IGF-1 is the adult form of IGF, whereas IGF-II is the fetal form.

Just like GH, IGF has a range of functions. It regulates carbohydrate metabolism and stimulates amino acid uptake and protein synthesis. It also has profound effects on growth and acts as a mitogen (something that can stimulate proliferation of target cells). IGF can potentiate the effects of GH, making it more effective.

Throughout puberty, GH and IGF levels increase simultaneously. IGF peaks at adolescence- teenagers have around three times as much IGF as adults!

As I mentioned earlier, both GH and insulin can stimulate IGF release. This can be used to explain why amino acids and glucose can stimulate growth. High amino acid levels stimulate growth hormone release, increasing IGF levels. High glucose levels stimulate insulin, which also increases IGF levels. Therefore, growth occurs when nutrients are plentiful. On the other hand, if glucose is low, IGF production can decrease, impairing growth even if GH levels are high.

Just like with GH, IGF levels are also controlled by negative feedback. High IGF1 decreases GH secretion by increasing somatostatin release from the hypothalamus, suppressing release of GH from the anterior pituitary.

Other important growth factors

Steroid hormones, such as androgens, can be important in growth. Androgens can stimulate protein synthesis. Furthermore, testosterone and oestrogen can act synergistically with GH in order to stimulate growth of more GH. In turn, GH can potentiate some of the effects of the sex steroids.

Thyroid hormones, particularly T3, are also important in growth. They do not cause growth on their own, but stimulate GH synthesis and secretion. T3 may also increase the responsiveness of target cells to GH.

Outline abnormal control of growth – implications and disease states

Over-secretion of GH

Over-secretion of GH can cause gigantism if it occurs before puberty (as epiphyseal plates haven't closed yet), or acromegaly (thickening of bones) if it occurs after puberty. In acromegaly, growth of bone and cartilage can compress nerves. Therefore, symptoms of acromegaly include visual field losses due to pressure on optic nerves, Bell's palsy (facial paralysis on one side) due to pressure on the facial nerve, and carpal tunnel syndrome due to pressure on the median nerve in the wrist. Acromegaly may also increase the risk of malignant tumours.

Under-secretion of GH

Under-secretion of GH can be caused by tumours that over-secrete somatostatin, infections and irradiation. Under-secretion of GH, or some other defect in the GH signalling pathway, results in dwarfism. Not everyone with dwarfism has the same defect: Laron Dwarfs have a genetic defect in GH receptor expression, and African pygmies have normal GH levels but impaired IGF production.

Hormonal growth promoters

Synthetic hormones are being used for various processes. In food production, they are used to promote growth and productivity. (There is some controversy surrounding this, but I'm not going to go into it.) Growth hormones can also be used therapeutically in the treatment of GH deficiencies as well as muscle-wasting disorders. Such synthetic growth hormones are banned in competitive sports, but that hasn't stopped people from producing GHRH peptides, which act on the pituitary gland to stimulate GH secretion. Hormone replacement therapy has also been suggested in reducing bone and muscle loss in ageing, but there is a risk of serious side-effects since you are essentially inducing acromegaly.