Somatotropic axis

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 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

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

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

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 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

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