Growth hormone
• Pituitary protein hormone– 191 amino acids
• 22 kDa
– Non-glycosylated– Two disulfide bridges
• Shares homology with prolactin, placental lactogen, and GH-variant– 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