Somatotropic axis

Document technical information

Format ppt
Size 1.6 MB
First found May 22, 2018

Document content analysis

Category Also themed
Language
English
Type
not defined
Concepts
no text concepts found

Persons

Organizations

Places

Transcript

Somatotropic axis
Growth hormone
• Pituitary protein
hormone
– 191 amino acids
• 22 kDa
– Non-glycosylated
– Two disulfide bridges
• Shares homology with
prolactin, placental
lactogen, and GHvariant
– Gene duplication
• Human GH gene
– Located in chromosome 17
• 66 kb in length
• Cluster of genes that encode closely related genes
– GH-V
– Placental lactogen/chorionic somatotropins
– Transcription of GH mRNA
• POUF1 transcription factor
– Pituitary specificity
– Interacts with protein kinase A pathway
Secretion pattern
• Pulsatile manner
– Interplay between GHRH
and SS
– Other GH secretagogues
– Release of GH in response
to GHRH
• Elevation of cAMP
• GHRH
– Critical for development
and maintenance of
somatotrophs
• Hypersecretion results in
pituitary tumor
development
• Role of SS
– Affects timing and amplitude of pulsatile GH secretion
• Pulsatile GH
– Diminished secretion of SS coupled with increased GHRH
secretion
• Trough GH
– Diminished secretion of GHRH coupled with increased SS
secretion
• Nature of GHRH/SS regulation of GH secretion
– Somewhat unclear
• Involvement of numerous neurotransmitters
Regulation of GH secretion
• Major GH pulses (70 % of total daily
output)
– Slow sleep (deep sleep)
– Age-related loss of GH
• Decrease quality of sleep
• Obesity and diabetes
– Decreased GH release
– Nutritional status
• One of the major regulatory factor of GH secretion
• Gender-specific pattern of GH secretion
– Affects amount of steroidogenic enzymes
• Gender-specific pattern of steroidogenesis
– Gender-specific pattern of liver enzyme
expression
– Gender-specific action of GH
• Mediated by STAT 5b activity
Effects of growth hormone
• Growth of epiphyseal plate in the long
bones
– Incorporation of sulfur into the epiphyseal
cartilage
• Sulfation factor
• Indirect action of GH (delayed response)
– Requirement of mediator(s)
• Somatomedins
Action of GH
• Mediated by Insulin-like growth factors
(IGFs)
– Two types
• IGF-I
• IGF-II
– Structurally similar to preinsulin
• Interact with insulin receptor when in high
concentrations
• IGF-II
– Developmentally important
– Declines with age
– Secretion independent of GH in many species
• IGF-I
– Mediation of growth
– Endocrine
• Liver
– Local (autocrine/paracrine) IGF-I
– Secretion depends on GH
• Importance of IGF-I
– Total deletion (knockout)
• Postnatal lethality
– 32-95 % die within 24 hr postpartum
– Muscular dystrophy and premature lung development
• Growth retardation
– Embryonic
– Postnatal (35 % less than that of normal)
• Infertility
– Impaired steroidogenesis
• Endocrine IGF-I
– Potent inhibitor of GH synthesis and secretion
– May not be essential for normal growth
• Local IGF-I
– Important for normal growth and development
– Important for ovarian function
• Steroidogenesis
– Synergizes with gonadotropins
• Cell proliferation
×

Report this document