What is the primary regulator of growth and lactation (in ruminants)?
GH/ Insulin-like growth factor-1
What is in charge of controlling (inhibiting) GH?
Where are GHRH and GRH secreted into, and where are the receptors?
Growth hormone releasing hormone (GHRH) -GH releasing factor (GRF)
-Secreted into hypothalamic-pituitary portal vein
-44 amino acids (29 AA active core)
-High homology among species (2-3 AA variation)
-->Receptors located on anterior pituitary
Stimulates GH synthesis, secretion -storage vesicles
What is GHIH (also referred to as somatostatin)?
Where is it secreteds, where are the receptors?
GH-inhibiting hormone (GHIH); SRIH or SRIF
-Secreted into hypothalamic-pituitary portal vein
Two forms –overlap in activities. 14 AA –brain; 28 AA –GI tract
Very high sequence identity among species
--> Receptors located on anterior pituitary –inhibits GH release
Also produced in gut (70% of body somatostatin), pancreas, brain, neurons, immune cells, gonads, uterus
What are some other names for somatostatin in other species?
Bovine somatotropin (bST)
porcine somatotropin (pST)
Synthesis, secretion from anterior pituitary –approx. 200 AA
Species Homology: Ruminant GHs very similar (95-99% identity), Porcine GH 89% identity to ruminant, Chicken GH about 80% identity to ruminant, Human GH about 70% identity to ruminant GH --> Livestock species GH are inactive in humans
GH receptors located on liver, adipose, bone, muscle, gonads --> Not mammary epithelium
Are any hormones released in pulses?
Yes for sure!
When does Ghrelin mean?
What is its role?
“Ghre” means “grow” –reference to its ability to stimulate GH release
Increases appetite. Stimulates GH secretion. Produced by parietal cells of stomach. Receptors on anterior pituitary (GH) and hypothalamus (appetite). Secretion increased by fasting; decreased by feeding
What are the two direct GH effects to metabolism in the adipose tissue?
Metabolic effects in adipose tissue
-Anti-lipogenic effects –positive E balance. antagonizes insulin (anti-lipogenic)
-Lipolytic effects -potentiates epinephrine (negative E balance)
-->Stimulation of IGF-I secretion (with adequate nutrition). Liver, bone, muscle
What is IGF-1? What is its role?
IGF-1 has (50%) structural homology to insulin. Downstream signalling pathways, insulin-like effects.
Synthesized by most tissues- primarily liver --> No storage vesicles (secreted and synthesized as needed, therefore not secreted in pulses)
Receptors on most cell types. Endocrine, paracrine and autocrine activity.
Anabolic (promote protein synth) and mitogenic (promote cell proliferation in target tissues) in muslce, bone, mammary. Important in pre- and post-natal growth (IGF-1 peak at puberty and steadily decrease in adulthood with aging).
What is IGF-11? What is its role?
50% identity with insulin. 61% indentity with IGF-1
Synthesized by most body tissues- brain (major synthesis)
Receptors on most cell types (paracrine, autocrine and endocrine activity
Important in pre-natal growth. Role post-nantal not well understood.
What is IGFBP?
What does it do?
IGF- binding protein
Synthesized in most tissues including the liver.
Bind both IFG-1 and IGF-11. Higher levels of both hormones in blood
Main binding proteins secreted from liver IGFBP-3 --> Most abundand protein in blood, protects IGF from degreadation (10-15 min halflife of unbound) and functions as reservior for IGF-1
IGFBP-1, IGFBP-2 when bound to IGF BP can have a half life of 12-15 hour. Reduce tissue availability of IGF
What are the direct actions of GH?
Metabolic effects in adipose tissue.
Anti-lipogenic- antagonized insulin.
Potentiates epinepherine- increases lipolysis in neg- E balance.
Stimulation of IGF-1 secretion (with adequate nutrition)
--> liver, bone muscle
What are the indirect actions of GH?
Mediated by IGF-1
IGF-1. Mitogenic effects --> promotes cell proliferation
Anabolic activities- promotes protein synthesis, accretion
Mitogenic activities- promotoes cell proliferation, bone growth.
What is the effect of malnutrition of GH/IGF-1?
Malnutrition is the primary regulator of growth and lactation.
How do Male and Female sex change carcass composition due to the GH/IGF-1 axis?
Males: Testosterone stimulate plasma GH under good nutrition and increases GH pulsatility, which results in: -More efficent GH receptor internalization/recycling. -More potent in stimulating IGF-1 secretion. -Higher blood IGF-1 levels --> more lean growth.
Females; Estrogen also stimulates GH secretion and GH receptor number but with less potency than testosterone --> less lean growth
How do stress and infection tie into the GH/IGF-1 axis?
Stress- increased cortisol release. Reduced liver GH receptor number, liver IGF-1 synthesis. INcrease synthesis of IGFBP-1. --> ALL together it decreases [IGF-1] and therefore growth
Infection- Increased cytokine release. Reduced liver IGF-1 synthesis. Reduced appetite
We prioritize immune function over growth.
What do steriod implants in cattle do?
INCREASED MATURE BODY SIZE, INCREASED RIBEYE, REDUCED MARBLING.
Tesosterone and derivatives. Increase GH, GH receptor and pulsatility. Direct effect on muscle protein accretion.
Estrogen and derivatives. Increase GH, GH receptor and pulsatility. DIrect effect on muscle protein accretion?
Doses and combination determined by trial and error (use for cattle and sheep).
Where is the biggest IGF-1 response given in regards to diet?
A high energy and high protein diet
What does a mutation of the leptin gene result in?
Leptin (the obese gene)
Obese (50% of body weight is adipose).
Low matabolic acitivty.
Where is the leptin gene produced?
Produced and secreted almost exclusively in adipocytes
WHat are some general effects of Leptin?
Supresses appetite (major factor of feed intake) By making a neg feedback to tell them to stop eating, hypothalamic feeding centres.
Increases energy use (to decrease weight gain). Increases lipid/glucose use in liver and muscle. INcreases lipolysis, but decreases anabolic activites (protein synthesis).
Reproductive effects: Alters sensitivity of pitutary gland to GnRH- permits LH surge (surge responsible for ovulation). Links energy status with repord axis (thin vs normal animals).
What is positive energy balance?
When E expendature is less than E intake. Depositing adipose tissue.
What is the role of leptin in cattle?
More adipose tissue that is present the more leptin will be secreted.
Signals body fat mass
Secretion increase with increased fat mass
Signals energy balance
secretion decreases with decreased energy balance
secretion increases with increased energy balance
How does the lepting genotype affect carcass grade?
How does selection of breeding stock increase carcassing quality?
Leptin single nucleotide polymorphism
Feeding and management are optimized to a particular genotype of animal resulting in more homogeneous groups.
Myostatin and muscle hypertrophy
Myostatin produced by myocytes -Regulates muscle growth
Decreases protein synthesis. Increases protein degradation.
(for protein accretion to occur, need perotein synth to be higher than protein degredation)
Gene discovered in 1997 in mice –knockout “mighty mice”. Hyperplasia + hypertrophy
Natural mutations in myostatin gene results in animals lacking functional myostatin –increased muscle mass
What breeds does double-muscling occur?
Double-muscled cattle- Belgian Blue, Piedmontese (excessive muscle deposition)
Five mutations in myostatin gene identified in a number of different cattle breeds. Lack of functional myostatin. Muscle cells multiply, enlarge
Myostain and muscle hyperplasia?