Hormones that Affect Growth

1
Hormones that Affect Growth
2
(No Transcript)
3
Growth Hormone

• Somatotropin or growth hormone is a naturally
  occurring protein hormone.
• Release is controlled by hypothalmic factors
  known as growth hormone releasing factor.
• Growth hormone is released from the pituitary.
• Growth hormones affect on muscle is mediated
  through IGF-I and binding sites for the IGF-I.

4
Growth Hormone

• Growth hormone interacts with receptors on the
  cell membranes of the liver, kidney and muscle,
  causing the release of IGF-I into the
  circulation.
• IGF-I can stimulate proliferation and
  differentiation of myoblasts.

5
Hormonal Control of GH

• Higher brain centers activate the hypothalamus
• Hypothalamus releases either GNRH or somatostatin
  which affects the pituitary
• Pituitary releases somatotropin in response to
  GNRH
• Somatotropin acts on the Liver which releases
  IGF-I which in turn activates the target tissues
• IGF-I has a negative feedback on the pituitary
  and increases the release of somatostatin

6
Growth Hormone

• Direct effects of growth hormone
• Reduced glucose transport and metabolism
• Increased lipolysis
• Increased amino acid transport
• Increased protein synthesis
• Increased IGF-I production
• Increased fibroblast differentiation

7
Growth Hormone

• Indirect effects of growth hormone
• Promotion of growth and endocrine effects
• Reduction in insulin receptors in liver
• Localized decrease in adipose tissue free fatty
  acids released
• Increases in both transcription and translation
• Chondrocyte, osteobalst and adipocyte formation

8
Growth Hormone

• Bone Growth
• Growth hormone affect on bone is mediated through
  IGF-I.
• IGF-I increases chondrocyte proliferation and
  osteoblast activity.
• GH leads to increased bone length prior to
  epipyseal closure
• GH also increases periosteal growth contributing
  to increased bone mass

9
Growth Hormone

• Muscle Growth
• Increased rates of muscle protein synthesis
• Decreased protein degradation
• Increased RNA and DNA often accompanying the
  increased protein accretion.
• Increased DNA is likely a result of increased
  satellite cell activity.

10
Growth Hormone

• IGF-I increases uptake of glucose and amino acids
  into muscle.
• Various binding proteins are involved in
  transporting the IGF-I to the target tissues

11
(No Transcript)
12
Cellular Growth Factors
13
Androgens

• Two main androgens
• Testosterone male sex hormone
• Androstenone pheromone secreted from salivary
  gland. Compound responsible for boar taint.

14
Testosterone

• Increased body growth
• Adult levels stimulate epiphyseal plate closure
• Increased deposition of bone salts
• Increased testosterone postnatally contributes to
  larger fibers from induction of muscle protein
  accretion

15
Androgen Effect on Muscle

• Androgens bind to specific intracellular androgen
  receptors in muscle to increase protein synthesis
• Testosterone also may be aromatized to estradiol,
  so some effects of testosterone may be mediated
  through its estrogenic metabolites
• Androgens may interfere with the anti-anabolic
  effects of cortisol
• Androgen effects also may be mediated through
  growth hormone
• Androgens tend to increase both protein synthesis
  and protein degradation

16
Estrogens

• Estrone, Estriol, ?-Estradiol
• Adult levels stimulate epiphyseal closure via
  influences on chondrocyte proliferation and
  function and on bone formation
• Estrogens facilitate deposition of fat and
  stimulate muscle growth.
• Estrogens are most affective in castrated male
  ruminants in which they improve gain and feed
  conversion 10-20
• Estrogen decreases protein degradation

17
Insulin

• Increases storage of glucose, fatty acids, and
  amino acids as glycogen, triglycerides and
  proteins.
• Stimulation of cellular uptake of glucose, amino
  acids and lipids
• Stimulation of lipogenesis, glycogenesis, and
  protein synthesis

18
Glucagon

• Mobilization of glucose by increasing
  glycogenolysis and gluconeogenesis
• Mobilization of fatty acids by increasing
  lipolysis
• Increased amino acid catabolism

19
(No Transcript)
20
Leptin

• Leptin is a peptide hormone produced by adipose
  tissue.
• Leptin appears to provide signals to the
  hypothalamus that regulate multiple response
  mechanisms.
• An increase in adipose tissue mass results in
  concentrations of leptin that are sufficient to
  induce the hypothalmus to decrease food intake,
  increase energy expenditure and modulate other
  hormones that decrease lipogenesis and increase
  lipolysis.

21
(No Transcript)
22
Progestins

• Steroid hormones that imporve growth and feed
  efficiency in heifers
• MGA (melengestrol acetate) 100x more poteint than
  progesterone in stimulating growth inn feedlot
  heifers
• Effect probably related to suppression of estrus
  and its related problems.

23
Glucocorticoids

• Cortisol
• Glucocorticoids decrease muscle protein synthesis
  and increase muscle protein degradation in an
  attempt to make amino acids available for glucose
  production.
• They also increase lipolysis, in part, by
  enhancing GH-and catecholamine stimulated
  lipolysis

24
Catecholamines

• Epinephrine and norepinephrine
• These hormones act through adrenergic receptors
  (alpha1, alpha2, beta1, beta2 and beta3)
• Increased gluconeogenesis in liver
• Increased glycogenolysis in liver and muscle
• Increased lipolyisis in adipose tissue
• Epinephrine induces muscle anaerobic glycolysis

25
Thyroid Hormone

• Increases the metabolic activities of all or
  almost all of the tissues of the body
• Stimulates almost all aspects of carbohydrate
  metabolism
• Increased uptake of glucose by cells
• Enhanced glycolysis
• Enhanced gluconeogeneisis
• Increased rate of absorption from GI tract
• Decreases the quantity of cholesterol,
  phospholipids and triglycerides in the plasma
• Increases free fatty acids
• Extreme levels cause high basal metabolic rates

26
Growth Hormone

• Regulation of Growth Hormone Secretion
• Rate of GH secretion affected by stress and
  nutrition
• Starvation
• Hypoglycemia or low FA in blood
• Exercise
• Excitement
• Trauma
• Acute hypoglycemia is a potent stimulator of GH
  release
• Severe chronic protein deprivation results in
  high levels of circulating GH

27
Growth Hormone

• Regulation
• Hypothlamus
• Growth hormone releasing hormone
• Growth homone inhibitory hormone or somatostatin
• Other hormones also increase GH release
• Catecholamines
• Dopamine
• Serotonin

28
(No Transcript)
29
Growth Promotants

• Two broad groups
• Agents that alter the digestive process
• Agents that modify the way the animal uses or
  partitions nutrients for growth
• Agents that alter the digestive process
• More efficient energy absorption
• Increased protein digestibility and absorption
• Rumen modifies such as Rumensin

30
Growth Promotants

• Hormone Growth Promotants (HGP)
• Increase the use of nutrients for growth
• Most HGP are based on the steroid structure of
  natural sex hormones
• HGP may contain natural or synthetic copies of
  estrogen, androgens (testosterone)
• Most are administered in slow release implants

31
Beef Implants
32
Other Growth Promotants

• rPST, rBST Recombinant Somatotropin
• Exogenous growth hormone
• Injected into pigs increases muscle while
  decreasing fat
• Increases IGF-I and other hormones that modify
  growth and metabolism
• Increases milk secretion in lactating cows

33
Other Growth Promotants

• ? - Agonists
• Ractopamine (Paylean)
• Approved in 2000 goes under the trade name of
  Paylean
• Increases muscle mass
• Decreases fat
• Decreases tenderness

34
Concentration of Estradiol (E2) and Estrone (E1)
in Tissues of Steers Following Estrogen
Implantation
35
Daily Human 17-? Estradiol (E2) and Estrone (E1)
Production
36
Genetic Anomalies Affecting Growth

• Myostatin Gene Alterations
• Deletions causing reading frame shifts cause
  increased muscle hypertrophy resulting in a
  condition called double muscling
• Myostatin, the protein that the gene encodes, is
  a member of a superfamily of related molecules
  called transforming growth factors beta

37
Myostatin

• Breeds that have this change are Charlais,
  Piedmontese, Belgium Blues, and Blonde de
  Aquitane
• Cattle have only modest increases in muscle mass
  compared to the myostatin knockout mice (20-25)
  in the Belgian Blue and 200-300 in the null mice

38
Myostatin

• Homozygous mutant mice (often called knockout
  mice) were 30 larger than their heterozygous and
  wild-type (normal) littermates irregardless of
  sex and age
• Adult mutant mice had abnormal body shapes with
  very large hips and shoulders and the fat content
  was similar to the wild-type counterparts
• Individual muscles from mutant mice weighed 2-3
  times more than those from wild-type mice
• Histological analysis revealed that increased
  muscle mass in the mutant mice was resultant of
  both hyperplasia and hypertrophy

39
Myostatin

• Myoblasts in developing animal embryos respond to
  different signals that control proliferation and
  cell migration. In contrast, differentiated
  muscle cells respond to another set of different
  signals
• Distinct ratios of signals regulate the
  transition from undetermined cells to
  differentiated cells and ensure normal formation
  and differentiation in cellular tissues.

40
Myostatin

• MyoD, IGF-I and myogenin (growth promoters in
  muscle cells) gene products are associated with
  muscle cell differentiation and activation of
  muscle specific gene expression
• Muscle-regulatory factor 4 (MRF-4) mRNA
  expression increases after birth and is the
  dominant factor in adult muscle. This growth
  factor is thought to play an important role in
  maintenance of muscle cells

41
Myostatin

• In addition to myostatin, there are other
  inhibitory gene products, such as Id (inhibitor
  of DNA binding).
• In vitro experiments are revealing the mechanisms
  of myostatin and other regulatory proteins, less
  in known of their roles in vivo
• Studies strongly suggest that the physiological
  role of myostatin is mostly associated with
  prenatal muscle growth where myoblasts are
  proliferating, differentiation and fusing to form
  muscle fibers.

42
Genetic Anomalies Affecting Growth

• Callipyge Gene
• An inheritable muscular hypertrophy in sheep
  mapped to chromosome 18
• The callipyge gene is characterized by a
  nonmendelian inheritance patter, referred to as
  polar overdominance, where only heterozygous
  individuals inherit the callipyge mutation from
  their sire express the phenotype

43
Callipyge

• The phenotypic expression of the callipyge gene
  results in muscle specific hypertrophy.
• The developmental growth patterns of the muscles
  under callpyge gene control has not been well
  defined
• Growth rates of thoracic limb muscles not greatly
  influenced by the callipyge gene
• Growth rates of longissimus and psoas major are
  higher in callipyge lambs (37 and 27
  respectively)
• Growth rates of all pelvic limb muscles are also
  significantly higher in callipyge lambs the
  semimembranosus grew 45 faster in callipyge lambs

44
Callipyge

• Increased toughness has been associated with
  callipyge lambs
• The mechanism causing the increased toughness is
  not yet known
• The most likely culprit appears to be reduced
  fragmentation of muscle fibers during the
  postmortem aging.