Normal Growth and Clinical Aspects Flashcards
Summarise schematically the routes involved in the secretion and target effects of GH.
a
Define the term ‘somatotropin’.
(“trop” relating to growth)
AKA Growth hormone is released from the anterior pituitary. It helps to regulate growth.
Define the term ‘somatostatin’.
(“statin” relating to stasis)
AKA Growth hormone inhibiting hormone is one of two hypothalamic neurohormones, which control the release of GH.
Define the term ‘somatomedin’ and how it is similar to insulin.
Somatomedin C AKA insulin-like growth factor-1 (IGF-I) is a hormone that mediates the action of GH.
- Has a similar structure to proinsulin
- Binds to receptors similar to the insulin receptor
- Has hypoglycaemic qualities (limited to glucose uptake in muscle, liver/adipose tissue have few IGF receptors)
State the factors that regulate growth.
Growth hormone;
- Released from anterior pituitary
- Is regulated by balance of GRGH vs GHIH released from hypothalamus
- Thyroid hormones
- Insulin
- Sex steroids (especially at puberty)
- Availability of nutrients
- Stress
- Genetics
Besides GHIH, what other hormone helps to control GH release?
Growth hormone releasing hormone (GHRH), a hypothalamic neurohormone.
Describe the actions of GH.
GH has a wide spectrum of biological activity that can be defined by two broad categories;
- Growth and development (indirect action)
- Regulation of metabolism (direct action)
Describe the action of GH on growth and development.
GH is necessary for growth and development of the child. Growth in the foetal period and the first 8-10 months of life is largely controlled by nutritional intake, but thereafter GH becomes the dominant influence on the rate at which children grow.
What does GH require to stimulate growth?
GH requires permissive action of thyroid hormones and insulin before it will stimulate growth. Children with untreated hypothyroidism, or poorly controlled diabetes, have stunted growth despite normal GH levels.
Does GH secretion continue throughout adult life?
Yes - GH secretion continues throughout adult life as it is continues to be essential in the maintenance and repair of tissue.
What two things mediate the growth-promoting effect of GH?
Through stimulation of both;
- Cell size (hypertrophy)
- Cell division (hyperplasia)
in its many target tissues.
Explain why the effect of GH on growth is almost entirely indirect.
As it is achieved through the action of an intermediate known as insulin-like growth factor-I (IGF-I), AKA somatomedin C, as it mediates the action of GH.
Describe the secretion of IGF-I and its control of GH.
- Secreted by the liver and may other cell types in response to GH release
- Control GH release through a negative feedback loop/
IGF-II exists. True or false?
True, however its functional importance appears to be limited to the foetus and neonates.
What type of hormones are GH and IGF-I?
Peptide hormones but like steroid and thyroid hormones, they are transported in the blood bound to carrier proteins.
Approx. 50% of GH is in the bound form. This helps to provide a “reservoir” of GH in the blood, which helps to smooth out the effects of the erratic pattern of secretion and extends half life by protecting it from excretion in the urine.
Describe the IGF-I negative feedback loop on GH release.
IGF-I exhibits negative feedback on GH release both via inhibiting GHRH and stimulating GHIH.
Additional negative feedback loop of GH on GH release from somatotrophs in pituitary.
Describe GH/IGF-I effects on bone growth.
- GH stimulates chondrocyte precursor cells (prechondrocytes) in the epiphyseal plates to differentiate into chondrocytes.
- During the differentiation, the cells begin to secrete IGF-I and become responsive to IGF-I.
- IGF-I then acts as an auto/paracrine agent to stimulate the differentiating chondrocytes to undergo cell division and produce cartilage, the foundation for bone growth.
Describe the action of GH on the regulation of metabolism.
- Increases gluconeogenesis by the liver.
- Reduces the ability of insulin to stimulate glucose uptake by muscle and adipose tissue.
- Makes adipocytes more sensitive to lipolytic stimuli.
However, unlike cortisol and just like insulin, GH:
4. Increases amino acid uptake and protein synthesis in almost all cells = anabolic effect (cortisol stimulates protein catabolism).
Describe the action of GH on the regulation of metabolism.
- Increases gluconeogenesis by the liver.
- Reduces the ability of insulin to stimulate glucose uptake by muscle and adipose tissue.
- Makes adipocytes more sensitive to lipolytic stimuli.
In all of these actions, GH is releasing energy stores to support growth. (Remember only fat and muscle require insulin for glucose uptake – bone does not). It is having an “anti-insulin” effect and synergises with cortisol in this respect.
GH is therefore said to be diabetogenic (increases blood glucose) when present in XS.
However, unlike cortisol and just like insulin, GH:
4. Increases amino acid uptake and protein synthesis in almost all cells = anabolic effect (cortisol stimulates protein catabolism).
Insulin and GH are anabolic hormones. Describe their effect on aa uptake, protein synthesis and glucose uptake.
Insulin;
- Increased aa uptake
- Increased protein synthesis
- Increased glucose uptake
GH;
- Increased aa uptake
- Increased protein synthesis
- NO EFFECT ON glucose uptake
Describe the daily changes in GH secretion.
- Majority of GH released during first 2 hours of sleep (deep delta sleep)
- 20x increase in GH secretion in children during this period
- General energy requirements low so energy diverted to growth
- GHRH may have sleep inducing qualities
- GH release during waking hours is low
- Despite GH spikes, [IGF-I] in plasma remain relatively constant suggesting IGF-I buffers the pulsatile variance in GH levels.
Describe the control of GH secretion.
Control of GH secretion is heavily influenced by nutritional status, as expected given the role of GH in regulating metabolism. Nutritional control of GH release is mainly mediated via modulation of control of GHRH/GHIH release from the hypothalamus.
Describe how GH is diabetogenic.
During its regulation of metabolism, GH is releasing energy stores to support growth. (Remember only fat and muscle require insulin for glucose uptake – bone does not). It is having an “anti-insulin” effect and synergises with cortisol in this respect.
GH is therefore said to be diabetogenic (increases blood glucose) when present in XS.
Explain how an actual or potential decrease in energy supply to cells increases GHRH secretion.
As well as growth and development, GH is needed for maintenance of tissues and their energy supply.
Fasting and hypoglycaemia = decrease in substrate supply.
In exercise and in the cold = increase demand for energy. All stimulate increase in GH.
