Somatotropic Axis Flashcards
Outline the pathway of the somatotropic axis
Hypothalamis hormone is GHRH
Anterior Pituitary hormone is GH
>inhibited by GHIH
Endocrine target is the liver which secretes IGFs
Non-Endocrine target is many tissues
Overview of Somatotropic Axis
GHRH
Hypothalamus & Paraventricular Nucleus secrete GHRH (Somatostatin)
Anterior Pituitary secretes GH (Somatotropin) which acts on the liver
Liver creates IGF-1,2 (Somatomedians) which acts on cartilage
Background on GH
Protein
Half-life: 6-20 min
Most abundant anterior pituitary hormone (10x more)
Plays an important role in growth
191AA polypeptide, synthesized, stored and secreted by somatotropic cells in the lateral wings of the anterior pituitary gland
GH secretion patterns
GH secretion occurs as several large pulses or peaks each day, 10-30 minutes in duration
The largest GH peak occurs about 1 hour after onset of sleep (Circadian Pattern)
Lifetime : basal levels highest early in life; the amplitude and frequency of peaks are greatest during the pubertal growth spurt and then decline throughout adult life
What keeps growing throughout your whole life ?
Cartilage
ie/ nose and ears
GH : transport in blood
GH may be transported as free hormone but much of GH is bound to binding protein (GHBP)
Which regulators of GH INCREASE secretion ?
hint : 6
- Sleep
- Exercise
- Hypoglycemia
- High dietary protein
- Steroids
- Ghrelin
Which regulators of GH DECREASE secretion ?
- Hyperglycemia
- Glucocorticoids
- Endocrine disruptors
How are IGF-1 transported in blood
IGF-1 is almost entirely bound to transport proteins (IGF-BP’s)
Some IGF-1 transport/binding proteins have an endocrine function (ie/ there are receptors for these proteins)
The physiological roles of GH and IGF-1
GH stimulates the synthesis and release of IGF-1 in many tissues, not just the liver
> therefore, it is very difficult to differentiate between the direct actions of GH and those of IGF-1
HOWEVER, GH and IGF-1 appear to exert opposite actions in some tissues which suggests that they do have independent roles
what does GH do to liver glucose release ?
Increases release
What does IGF-1 do to liver glucose release ?
Decrease
What does GH do to plasma glucose concentration ?
Increase
What does IGF-1 do to plasma glucose concentration ?
Decrease
What does GH do to the sensitivity of tissue to insulin ?
Decrease
What does IGF-1 do to sensitivity of tissue to insulin ?
Increase
What does GH do to lipolysis in adipocytes ?
Increase
What does IGF-1 do to lipolysis in adipocytes ?
Decrease
What does GH do to muscle amino acid uptake & protein synthesis
Increase
What does IGF-1 do to muscle amino acid uptake & protein synthesis
Increase ? **unproven
What are the metabolic effects of GH
Acts on liver, adipose tissue and most tissue
Liver creates IGF-1 which works stimulates cartilage and bone growth and stimulates protein synthesis growth in muscle and other organs
In adipose tissue it encourages lipolysis release of fatty acids and it decreases glucose utilization in most tissues
How do children grow ?
Children have 2 periods of rapid growth: postnatal & puberty
Children grow unproportionate
Will children grow normally without GH ?
GH (somatotropin) is made in the anterior pituitary
It is released throughout life, though its biggest role is in children, and peaks during teenage years.
GH stimulates growth of:
1) bone & cartilage growth
2) soft tissue growth
- hypertrophy (increased cell size)
- hyperplasia (increased cell number)
How is bone formed ?
Bone contains calcified ECM formed when calcium phosphate crystals precipitate and attach to a lattice support.
The most common form of calcium phosphate is HYDROXYAPATITE
Bone forming cells are called OSTEOBLASTS
How does bone grow ?
Bone DIAMETER increases; when growth occurs around the bone. Matrix deposits on the outer surface of bone
Bone LENGTH increases; when growth occurs at EPIPHYSEAL PLATES
How does linear bone growth from epiphyseal plates work ?
The epiphyseal plates are near the end of the bone contains CHONDROCYTES; columns of collagen-producing cells
As the collagen layer thickens, the old cartilage calcifies
CHONDROCYTES then degenerate
Osteoblasts invade and lay bone matrix on top of the cartilage base
Overall affect of GH on bone growth
GH directly stimulates chondrocytes
GH stimulates production of IGF-1 in liver
IGF-1 helps stimulate chondrocyte & osteoblast activity, to promote bone
GH-related disorders: underproduction or decreased sensitivity in growing animals
Result is :
pituitary dwarfism;
- small size, juvenile proportions
- normal shape at maturity but stunted
pygmies (laron-type dwarfism);
- decreased responsiveness to GH (receptor deficieny)
GH-related disorders:
Overproduction of GH in growing animals
Pituitary Gigantism
GH-related disorders:
underproduction or decreased sensitivity in adults
Alopecia
Thin skin, hair loss
Cushing’s syndrome
increase in cortisol inhibits GH synthesis
GH-related disorders:
over production in adults
Acromegaly
> thickening of bones/joints and skin
> enlargement of internal organs (tongue, liver, spleen)
Progression of GH deficiencies in children vs adults
Severe GH (or GHR) deficiency in childhood - dwarfism
Oversecretion of GH in children- gigantism
Oversecretion in adults - acromegaly
