normal Growth and Clinical Aspects

Question 1

how is growth regulated?

Answer 1

Growth hormone release from anterior pituitary – which in turn is regulated by the balance of GHRH vs GHIH release from the hypothalamus
Thyroid hormones
Insulin
Sex steroids (esp. at puberty)
Availability of nutrients
Stress
Genetics

Question 2

what is a growth hormone?

Answer 2

a peptide hormone released from the anterior pituitary. Aka somatotropin (“trop” relating to growth).

Question 3

how is growth hormones controlled?

Answer 3

via the release of two hypothalamic neurohormones with opposing action:
Growth Hormone Inhibiting Hormone (GHIH) (aka Somatostatin (“statin” relating to stasis = static/stopped))
and
Growth Hormone Releasing Hormone (GHRH)

Question 4

what determines the balance of growth hormone inhibiting hormone and growth hormone releasing hormone?

Answer 4

by the myriad of factors that impinge on the hypothalamus.

Question 5

what are the actions of growth hormone?

Answer 5

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)

Question 6

what does GH require?

Answer 6

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.

Question 7

true or false:

Growth-promoting effect of GH is mediated through stimulation of both cell size (hypertrophy) and cell division (hyperplasia) in its many target tissues.

Answer 7

true

Question 8

how does the growth hormone work?

Answer 8

The effect of GH on growth is almost entirely indirect, being achieved through the action of an intermediate known as insulin-like growth factor-I (IGF-1) aka somatomedin C as it mediates the action of GH.

Question 9

what secretes IGF-1?

Answer 9

liver, in response to GH release, and IGF-1 controls GH release through a negative feedback loop

Question 10

how does IGF exhibit negative feedback on GH release?

Answer 10

via inhibiting GHRH and stimulating GHIH

Question 11

what are the GH/IGF-1 effects on bone growth

Answer 11

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 to become responsive to IGF-I

IGF-I then acts as an autocrine or paracrine agent to stimulate the differentiating chondrocytes to undergo cell division and produce cartilage, the foundation for bone growth.

Question 12

what are the direct effects of GH?

Answer 12

Increases gluconeogenesis by the liver.

2. Reduces the ability of insulin to stimulate glucose uptake by muscle and adipose tissue.
3. 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).

Question 13

what is the control of GH secretion heavily influenced by?

Answer 13

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.

Question 14

whatare stimuli that increase GHRH secretion?

Answer 14

Actual or potential in energy supply to cells. As well as growth and development GH needed for maintenance of tissues and their energy supply. In fasting and hypoglycaemia  in substrate supply. In exercise and in the cold  demand for energy. All stimulate  GH.

2. Increased amounts of amino acids in the plasma, eg protein meal. GH promotes amino acid transport and protein synthesis by muscle and liver.
3. Stressful stimuli eg infection, psychological stress
4. Delta sleep in GH in delta sleep may be related to growth spurts in children and adolescents and tissue repair in adults.
5. Oestrogen and testosterone stimulate GH release from the pituitary directly as well as decreasing IGF mediated negative feedback. Responsible for growth spurt in puberty.

Question 15

what are stimuli that increase GHIH (decrease in GH)

Answer 15

Glucose

2. FFA
3. REM sleep (Subjects deprived of REM sleep have  GH secretion)
4. Cortisol (although inhibitory effect on growth may be more to do with  protein catabolism than stimulating GHIH release)

Question 16

what are the 3 factors that effect the physiology of growth?

Answer 16

Hormones
Nutrition
Genetics

Question 17

what are the two periods of rapid growth?

Answer 17

Infancy: amazing growth spurts 2.5cm in a few days and then nothing i.e. episodic, mechanism not known.

2. Puberty: due to androgens and oestrogens, produce spikes in GH secretion that IGF-I  growth. The same sex steroids also terminate growth by causing the epiphyses of the long bones to fuse.
   So, in normal puberty, before the epiphyseal plates fuse, GH/IGF-I promote bone elongation and increased height, weight and body mass.
   Sex hormones in the later stages of puberty act to close the epiphyses and hence stop bone elongation.

Question 18

what is the common cause of hypersecretion of GH

Answer 18

endocrine tumours

Question 19

what is gigantism?

Answer 19

XS GH due to a pituitary tumour before epiphyseal plates of long bones close excessive growth, may be more than 7ft tall (210cm), called pituitary giants

Question 20

what is acromegaly?

Answer 20

XS GH due to a pituitary tumour after epiphyseal plates have sealed. Long bones cannot increase so there is no longitudinal growth and no increase in height. However, can still grow in other directions and the characteristic features are enlarged hands and feet.

Question 21

what is a classic sign of acromegaly?

Answer 21

adults feed get bigger