1. Somatotropic axis

2. 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

3. Human GH gene Located in chromosome 17 Transcription of GH mRNA
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

4. Secretion pattern Pulsatile manner GHRH 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

5. Nature of GHRH/SS regulation of GH secretion
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

7. 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

8. 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

9. 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

10. 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

12. IGF-II IGF-I 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

13. 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

15. Endocrine IGF-I Potent inhibitor of GH synthesis and secretion
May not be essential for normal growth

19. Local IGF-I Important for normal growth and development
Important for ovarian function
Steroidogenesis
Synergizes with gonadotropins
Cell proliferation