Hormonal growth Flashcards
GHRH
- Growth hormone-releasing hormone
- hypothalamic secretion into the hypothalamic-pituitary portal vein
- 44 amino acids
- receptors are located on the anterior pituitary
- stimulates GH synthesis secretion ( secretion of Gh from storage vesicles
somatostatin
- inhibitor of acid and motility of insulin
- hypothalamic secretion into hypothalamic-pituitary portal vein
- two different forms - 14 amino acids or 28 amino acids
- sequence identity among mammals, a very old pathway that hasn’t changed much
- high identity among species including sea anemone
- receptors located on anterior pituitary
- potent inhibitor of GH secretion ( not synthesis)
- also produced in gut ( 70% of body somatostatin)
- pancreas, brain, neurons, immune cells, gonads and uterus
Growth hormone
- somatotropin, bovine (BST), procine (PST)
- synthesized stored and secreted from anterior pituitary ( specialized cells = somatotropes)
- Gh receptors are located in the lvier, adipose, bone, muscle and gonads
hypothalamic control of GH secretion
- GHRH/SRIF control of GH secretion
- episodic hypothalamic secretion
- 180 out of phase
- Gh secretion is pulsatile
stomach
- ghrelin - stimulates hunger and growth hormone
- growth hormone releasing peptide
- produced by enteroendocrine cells of the stomach
- major role in energy homeostasis ( increases appetite and stimulates GH secretion)
- receptors located in hypothalamus (appetite) and anterior pituitary (GH)
- blood ghrelin increased by fasting decreased by feeding
insulin growth factor
- IGF I and IGF II
- IGF I
- 50% amino acid identity with insulin
- 61% identity with IGF II
- synthesized by most tissues ( no storage vesicles, highest levels by far in the liver)
- receptors on most cell types ( endocrine, paracrine and autocrine activity)
- anabolic and mitogenic in muscle, bone and mammary ( for pre and post natal growth)
IGF binding proteins
synthesized in most tissues including liver
- bind both IGF I and IGF II
high levels of both hormones in blood
- main binding proteins secreted from liver, reduces tissue availability of IGFs
- IGFBP-3 most abundant binding protein in blood
- protests IGF from degradation and functions as reservoir
direct actions of GH
metabolic effects in adipose tissues ( fat/ fatty tissue has receptors for growth hormone)
- anti-lipogenic/lipolytic activities
- antagonizes- the action of insulin through glucose/energy uptake to stop high energy balance
- potentiates epinephrine (stimulates the energy uptake, amplifies epinephrine, with negative energy = increase energy release from storage
- stimulation of IGF I secretion (with adequate nutrition) liver, bone muscle
indirect actions of GH
- mediated by IGF I
- IGF I has mitogenic activities (cell proliferation)
- promotes bone growth
- promotes protein synthesis and accretion
effects of nutrition on GH/IGF-I
- Gh secretion = increased secretion with undernutrition, gherkin mediated (fasting), reduced inhibitory factor
- GH receptors on liver: reduced number of GH receptors with undernutrition (uncoupling effect) (due to lower protein synthesis and lower expression in liver)
- IGF I secretion from liver: reduce secretion with undernutrtion, lower GH receptors number = lower expression in liver
- IGF I binding proteins - increased IGFBP 1 and 2 with lower nutrtion decreased IGFBP3
males
- testosterone stimulates plasma GH under good nutrition and increase GH pulsatility which results in
- more efficient GH receptor internalization/ recycling ( testosterone IGF 1 secretion and increase level of receptor stimulation more testosterone = more GH
- 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 and less lean growth
stress
- increase cortisol release
- reduces liver GH receptor number
- reduces liver igf I synthesis (slows down transcription and translation)
- increase synthesis of IGFBP 1
all combined - lower IGF 1 (grow less with stress)
infection
- increased inflammatory cytokine release ( protein hormones that control cells )
- reduced liver IGF I synthesis ( those released in earlt infection)
- reduced appetite ( see nutrition, one of the first things that goes during infection)
steroid implants in cattle
- increase mature body size, increased ribeye, reducing marbling
- testosterone and derivatives ( increase Gh, GH receptor and pulsatility, direct effect on muscle - increased protein accretion)
- estrogens and derivatives ( increase Gh, GH receptor and pulsatility, direct effet on muscle protein accretion)
- doses and combinations determined by trial and error
- cattle and sheep increase, no response in intact pigs
leptin
- hormone discovered in mice in 1994 using mutant obese mice
- mutation resulted in the secretion of a non function leptin
- hormone procudtion of the obese gene
- produced and secreted almost exclusively in adipocytes
- administration of leptin to obese mouse results in normal phenotype
signs of non functioning leptin
- obese: 50fi of body weight is adipose
- hyperphagic : normal mouse 4g/d obese mouse 14 g/d
- hypo active
- low metabolic activity ( all the energy is going to adipose ( body temp is 35C))
leptin general actions
- suppresses appetite ( directly modifies hypothalamic feeding centres)
- increases energy use( increases lipid/glucose use in liver and muscle, increases lipolysis, but decreases anabolic activities (protein synthesis)
- permissive role in reproductive cycling
- permits LH serge ( if females has adequate fat stores it helps with lactation, leptin allows for offspring to have energy in the form of fat)
- increase immune cell activity
plasma leptin
positively correlated with adiposity ( increased secretion with adipocyte size, leptin release per gram tissue 2x greater in obesity vs lean)
- positively correlated with energy balance ( reduced secretion as energy balanced decreases, energy balance overrides adiposidty for control of leptin
2x higher in females
role of leptin in cattle
- signals body fat mass ( secretion increases with fat mass)
- signals with energy balance ( secretion decreases with descrease in energy balanse, same in increases)
- metabolic response to increased leptin secretion in finishing steer
- decreases appetite
- altering energy metabolism and nutrient partitioning
- less energy available (lower intake)
increase energy production (metabolism of glucose and lipid ) in liver and muscle without increasing protein deposition - overall slower growth rate
- consider other production stages (lactation, gestation and cold exposure)
mutation identified in cattle leptin affecting function
- T allele = cys at position 4
- c allele = arg at postion 4
- selection of breeding stock for increased carcass quality
- genotype-specific management - feeding and management are optimized to a particular genotype of animal resulting in more homogenous groups
myostatin and muscle hypertrophy
- belgian breed with double muscling : 11 base pair deletion in exon 2 of myostatin on chromosome 2
- 5 mutations in myostatin gene identified in a number of different cattle breeds
- myostatin is a specific inhibator of muscle development
hyperplasia
- indentification of gene creates new opportunities for enhancing muscle growth
- diagnostic tests for genetic selection
- myostatin receptor blockers ( pharmacological and immunological
