Enrico Tiepolo
Growth and development GHRH, SRIF, GH
Somatic development is under control by growth hormone (GH, somatotropin, HGH).
• Growth hormone is a polypeptide folded on itself by two cys-cys bonds.
• It is released by the pituitary gland in response to GHRH
• It is inhibited by somatostatin (SST) and IGF-1
• Its aim is to promote growth at any cost: synthesis of proteins, mobilization of FAs for anabolism,
promote gluconeogenesis, and insulin resistance. It tends to increase glycemia, but glucose
uptake especially by muscles as well.
• Ghrelin also induces GH release, by acting directly on the pituitary, inducing GHRH release
and antagonizing SST.
• Average levels of GH are quite high at birth and gradually decline during the first 20 years,
stabilizing thereafter at about 1/10 of the initial levels. In adult life, GH levels tend to be lower
and undergo more frequent and larger oscillations in females. Anyway, GH never switches
off.
GH effects on the various organs can be summarized. Growth hormone directly activates hepatocytes,
skeletal muscle and adipose tissue (possibly the kidney as well):
a. Liver and its hepatocytes, in response to GH, release insulin-like growth factor 1 (IGF-1). In
addition to producing release of IGF-1, GH directly activates glycogen lysis in the hepatocyte
and therefore release of glucose into the circulation and hyperglycaemia.
b. Skeletal muscle (and also possibly kidneys and adipose tissue), in response to GH, also produce
IGF-1 with an autocrine function.
Exercise intensity may play a key role in triggering serum
GH concentration increase.
A threshold concept has been proposed, which may
correspond to the lactate threshold (LT). Although the
lactate threshold is defined as the point when lactic acid starts to
accumulate (curvilinear shift in Lactate vs. intensity), some
testers approximate this by using the point at which lactate
reaches a concentration of 4 mM (at rest it is around 1
mM).
= intense (anaerobic) exercise is needed to produce
muscular hypertrophy
Anaerobic activity, especially eccentric contraction, is what produces muscular trophism, while aerobic
activity is more important for consuming energy and burning fat. Release of NO, activating guanylyl
cyclase, also contributes to trophism by activating some pathways and downstream transcriptional
activity.
c. GH has a direct effect on adipose tissue by inhibiting lipogenesis and promoting a
metabolic shift towards beta oxidation of FA, to preserve glucose for other functions in
all cell types in general. In particular, this metabolic shift would allow us to use fats as energy
and leave glucose for anabolic destinies such as protein synthesis and others.
o Inhibition of lipogenesis = promotion of lipolysis à release of FFA.
o Glycogen lysis in hepatocytes for the release of glucose in the blood.
o Glucose is implied in anabolism, especially protein synthesis.
The effects of GH on adipose tissue, muscle and kidneys are direct (GH directly acts on them), but can
be considered partially indirect since they involve the production of IGF-1.
d. Long bones (their epiphyseal plate), under IGF-1 stimulation (produced by the liver when GH
is released), grow; this is why dwarfism develops in GH-lacking subjects; the interaction of
13 Body At Work II
Growth and development GHRH, SRIF, GH
Somatic development is under control by growth hormone (GH, somatotropin, HGH).
• Growth hormone is a polypeptide folded on itself by two cys-cys bonds.
• It is released by the pituitary gland in response to GHRH
• It is inhibited by somatostatin (SST) and IGF-1
• Its aim is to promote growth at any cost: synthesis of proteins, mobilization of FAs for anabolism,
promote gluconeogenesis, and insulin resistance. It tends to increase glycemia, but glucose
uptake especially by muscles as well.
• Ghrelin also induces GH release, by acting directly on the pituitary, inducing GHRH release
and antagonizing SST.
• Average levels of GH are quite high at birth and gradually decline during the first 20 years,
stabilizing thereafter at about 1/10 of the initial levels. In adult life, GH levels tend to be lower
and undergo more frequent and larger oscillations in females. Anyway, GH never switches
off.
GH effects on the various organs can be summarized. Growth hormone directly activates hepatocytes,
skeletal muscle and adipose tissue (possibly the kidney as well):
a. Liver and its hepatocytes, in response to GH, release insulin-like growth factor 1 (IGF-1). In
addition to producing release of IGF-1, GH directly activates glycogen lysis in the hepatocyte
and therefore release of glucose into the circulation and hyperglycaemia.
b. Skeletal muscle (and also possibly kidneys and adipose tissue), in response to GH, also produce
IGF-1 with an autocrine function.
Exercise intensity may play a key role in triggering serum
GH concentration increase.
A threshold concept has been proposed, which may
correspond to the lactate threshold (LT). Although the
lactate threshold is defined as the point when lactic acid starts to
accumulate (curvilinear shift in Lactate vs. intensity), some
testers approximate this by using the point at which lactate
reaches a concentration of 4 mM (at rest it is around 1
mM).
= intense (anaerobic) exercise is needed to produce
muscular hypertrophy
Anaerobic activity, especially eccentric contraction, is what produces muscular trophism, while aerobic
activity is more important for consuming energy and burning fat. Release of NO, activating guanylyl
cyclase, also contributes to trophism by activating some pathways and downstream transcriptional
activity.
c. GH has a direct effect on adipose tissue by inhibiting lipogenesis and promoting a
metabolic shift towards beta oxidation of FA, to preserve glucose for other functions in
all cell types in general. In particular, this metabolic shift would allow us to use fats as energy
and leave glucose for anabolic destinies such as protein synthesis and others.
o Inhibition of lipogenesis = promotion of lipolysis à release of FFA.
o Glycogen lysis in hepatocytes for the release of glucose in the blood.
o Glucose is implied in anabolism, especially protein synthesis.
The effects of GH on adipose tissue, muscle and kidneys are direct (GH directly acts on them), but can
be considered partially indirect since they involve the production of IGF-1.
d. Long bones (their epiphyseal plate), under IGF-1 stimulation (produced by the liver when GH
is released), grow; this is why dwarfism develops in GH-lacking subjects; the interaction of
13 Body At Work II
