8Distinguishing characteristic of endocrine systems: feedback control & hormone production.
9The paradigm for feedback control is the interaction of the pituitary gland with the thyroid, adrenals and gonads.Hormones produced in peripheral endocrine organs feedback on the hypothalamic-pituitary system > regulate the production of the trophic hormones that control peripheral endocrine glands.
13Adrenal gland develpment Embryology Mesoderm adrenal cortexEctoderm adrenal medulla5-6 wk fetal adrenal cortexOuter definitive zone (glucokortikoids and mineralocorticoids)Inner fetal zone (androgenic precursors)
14At birth AG is 0,5 % of total BW Glomerulosa 15 %Fasiculata 75 %Reticularis 10 %
15Fetal zone disappears around 1 years of age Glomerularis and fasiculata development is completed in 3 years.Reticularis development is completed in 15 years
16Fetal cortisol --> cortisone (Midgestation: cortisone (x4-5 cortisol))Cortisone: relatively inactive glucocorticoid; it protects the anabolic milieu of the fetus: cortisol can retard placental and fetal growth.As term approaches; liver, lung express 11-beta hydroxy steroid dehydrogenase I activity:cortisone --> cortisolCortisol: an important stimulus for preparing the fetus for extrauterine survival.
19Growth hormone The most produced hormone in the pituitary. Single chain alpha-helical nonglukolized polypeptide.Consists of 191 aminoacids and two intramolecular disulfide bounding.22kDa molecüler weight 75%20kDa 10-25%N-asetile ve desamine forms veya oligomers
25Human growth hormone (hGH) Nonpulsatile GH secretion in infants.During childhood 24 hour integrated GH secretion increase progressively.In puberty GH secretion amplitude increase to peak levels ( effect of gonadal steroids on GHRH).GH secretion decrease with age but secreted life long.
26GH-releasing peptides (GHRP)or secretagogues (GHS) Ligands that increase GH produced by humansDo not use GHRH or SRIF receptorsGHS-R G-protein associated recprotein kinase Chypothalamus, pituitary somatotrophs
27Ghrelin Endogen ligand for GHS-R. Increase GH secretion in rats (intracellular Ca increase).Physiologic mediator of nutrition
28GH effect Bound to GH-binding protein (GHBP) (at least 50 %) GHBP, is the extra cellular component of GH-R
29GH-R member of cytokine rec family 620 aa protein On plasma membrane. Extracellular part is transport proteinSingle transmembrans helixIntracellular part
30GH IGF’s (somatomedins) Similliar to proinsuline Effect on extrauterine growth via IGF-1ile (70aa polypeptide)
31Disorders associated with low IGF-1 levels GH deficiencyHypothyroidismMalnutritionChronic diseases
32Fetal IGF-1 is correlated with gestastional age Newborn IGF-1 levels are % of adult valuesIncrease through out childhood and reach adult levels in pubertyGonadal steroids increase IGF-1 production.In puberty levels are 2-3 fold higher than adult valuesIncrease osteoblastic activity and collagen synthesis stimulate long bone growth
33IGF’ s are bound to IGF binding proteins (IGFBP) Transport to target tissue.Modulate the relation with IGF rec6 different IGFBP are clonedIGFBP-3, 90 % related to GH
40Thyroid gland development Is derived from primitive pharynx-precursor of T4 producing cellsAnd fourth pharengeal pouch-precursor of calcitonin(C) cellsFor development and descent of thyroid several transcription factors such asTITF1/NKX2, FOXE1 and PAX 8 are needed to work on time and coordinated
41Embryogenesis After 1st month it is visable. At ıntrauterin 8 wk Tg synthesis begins shows thyroid activity10. wk iodine trapping12. wk colloid formation begins and withTSH sec from pituitary T4 synthesis beginsThis synthesis increase progresively with hypothalamic maturation after 18 wk of gestation
45Thyroid hormone synthesis ConjugationMIT + DIT T3DIT +DIT T4Thyroid peroksidase(TPO)
46TİROKSİN (T4) I I I I (fenol halkası) (tirozil halkası) COOH HO O CH2 5’6’56HO4’b1’O4a1CH2CHNH23’32’2IITip I-II monodeyiodinazTip III monodeyiodinaz5’ - monodeyidinasyon5 - monodeyidinasyonIIRRRROOIIIIT3rT3
53Iodine needs in different times of age Age and stages of lifeDaily idoine recommendation(g)6 <306-12 months401< years in iodine deficient regions901-10 years60-100Adoles and adults100Pregnant and lactating women150
55Iodine induced hyperthyoridism (Jodbasedow effect) Nodular thyroid disease with otonomy and with out antibodiesIodine induced hyperthyoridism(Jodbasedow effect)Diffuse goitre with thyroid stimulating antibodiesJodbasedow effect only in thyroids independent from TSH
56Iodine deficiencyIodine deficiency disorders (IDD) global heath problemWorld’s most common endocrine disorderMost frequent reseason for goitre and hypothyroidism