Slide 1Slide 2Slide 3Slide 4Slide 5Slide 6Slide 7Slide 8Slide 9Slide 10Slide 11Slide 12Slide 13Slide 14Slide 15Slide 16Slide 17Slide 18Slide 19Slide 20Slide 21Slide 22Slide 23Growth—•Hormonal influence: GH(+), TH(+), IN(+), sex H’s(+), GC’s(–)•Nutrition: adequate energy, protein (quant. & qual.), Ca2+, etc.•Genetic componentGrowth Hormone (aka somatotropin) [Ch. 23, pp. 787-89, incl. Fig. 23.8]•most important role is in growing children •peak secretion is in teenage yearsGrowth hormone– control of releaseHypothalamusAnt. PituitaryLiver, etc.GHRHGHCartilage, bone, tissue growthIGFnegativefeedbackSSTIGF↑bloodglucoseCircadian rhythm, stress, cortisol, circulating nutrients, sleep, exerciseGrowth Hormone—biological actions/effectsBinds to cell surface receptortyrosine kinaseActivation of signalingpathways controlling both long-term and acute effectsEffects of GH depend upon nutritional state—•Fed state (energy surplus): in concert with insulin/IGF, promotes nitrogen retention•Fasting/starvation (energy deficit): switches fuel consumption to predominantly fatty acid ox, while sparing glucose/protein Fed Fasting Møller N & Jørgensen JOL Endocrine Reviews 30:152-177, 2009Disorders of GH [pp. 788-9]•Dwarfism -- ↓GHRH/GH production ↓ end organ response; may or may not be associated with defects in other pituitary hormones•Giantism -- ↑↑ GH productionTreatment difficult due to 1) difficulty of diagnosing early enough; mustrecognize prior to first year, 2) GH may not be only defect•Acromegaly -- continued trophic effects on cartilage & soft tissues after bone growth plates have fusedthickening of cranium, mandible, facial bones, and bones of hands & feet; thickening of skin & disproportionate growth of some soft tissues, e.g. spleen, liver. Chronic GH secretion is diabetogenic [see Fig. 23.9, p. 789] Treatment:Tissue Growth – interaction of hormonal & paracrine signaling•GH/IGF: protein synthesis & cell proliferation—GH’s growth effects may be entirely mediated by IGF acting via both endocrine & paracrine mechanisms•GH/TH: protein synthesis & nervous system development—both production & action of GH are dependent upon T3•GH/Insulin: IN necessary for normal responsiveness to GH, esp. during fetal period•GH/androgens: Androgens may stimulate GH secretion, but also appear to have independent effects, esp. during adolescence•GH/estrogens: Complex interx’s; not well understood•GH/GC’s: GC’s req’d for GH production, but also have counter- (i.e. catabolic) effects•Other growth factors: EGF, PDGF, TGF’s, FGF, NGF, cytokinesBone Growth----fetus: begins as cartilage; changes to bone through ossification--infancy-early childhood: calcium & phosphorus laid down over cartilagenous matrix; bands of cartilage left at each end are growth plates--teenage years: bone grows longer with growth of new matrix at outer edge of growth plates while inner edge is converted to bone --20s+: growth ceases—cartilage synthesis stops, what remains is replaced by bone; continuous dynamic breakdown/renewal GH, IGFGH, IGF, sex steroidssex steroidsHydroxyapatite—Ca10(PO4)6(OH)2Non-growing bone undergoes continual dynamic remodeling—opposing actions of osteoblasts/osteoclasts•Androgens/estrogens, GH/IGF, Vit D, calcitonin favor bone formation; also need adequate dietary Ca2+•GC’s, Vit A, TH favor bone resorptionOsteoclast action – secreted HCl and cathepsins active at low pHdissolve bone and release Ca2+Bone mass balance:•Children: deposition > resorption•Young adults to age 30: deposition = resorption•30+: deposition < resorptionCalcium [Ch. 23, pp. 792-3,] Ca2+SignalingIntercellularadhesionBlood coagulationNeuronal excitabilityMusclecontractionMineralizationof bones & teethDaily Calcium Balance – overriding issue is regulation of plasma Ca2+ [Fig. 23.11]ICF9000 mgECF900 mgSecretion300 mgAbsorption400 mgDiet1000 mgFeces900 mgReabsorbed9900 mgFiltered10,000 mg600mgAccretion,Exchange, &Reabsorption600 mgUrine100 mgBONE990,000 mgParathyroid Hormone– effect on bone – via osteoblast-mediatedactivation of osteoclast differentiation [pp. 793-4]+-++++-+++Parathyroid Hormone– effect on kidney – 1) promotes Ca2+ reabsorption andPO4 excretion, and 2) activation of vitamin D (calcitriol) [p. 794]calcitriolVitamin D (calcitriol) –SynthesisFinal step occurs in kidney;stimulated by PTHCalcitriol – promotes Ca2+ absorption from intestine by stimulatingsynthesis of Ca2+-binding protein [p. 794] lumen Intestinal enterocyte bloodCalcitonin – counter-regulatory hormone for Ca2+ homeostasis [p 795]•Secreted from C-cells in thyroid in response to ↑ plasma Ca2+•Opposes PTH action in bone and kidneys•Appears to play minor role in adults, may be more important during childhood growth & preganacy/lactationOsteoporosis – bone resorption > deposition [p.