Distinguishing characteristic of endocrine systems: feedback control & hormone production.
The 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.
Adrenal gland develpment Embryology Mesoderm adrenal cortex Ectoderm adrenal medulla 5-6 wk fetal adrenal cortex Outer definitive zone (glucokortikoids and mineralocorticoids) Inner fetal zone (androgenic precursors)
At birth AG is 0,5 % of total BW Glomerulosa 15 % Fasiculata 75 % Reticularis 10 %
Fetal zone disappears around 1 years of age Glomerularis and fasiculata development is completed in 3 years. Reticularis development is completed in 15 years
Fetal 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 --> cortisol Cortisol: an important stimulus for preparing the fetus for extrauterine survival.
Development of pituitary gland
Growth 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
GH GH-BHBP Extracellular part of GH rec
Growth hormone Encoded by GH-1 gene. Locolized on 17q chromosome.
GH secretion Under control of 2 hypothalamic hormones Growth hormone releasing hormone(GHRH) Somatotropin release-inhibiting factor (SRIF, somatostatin)
GHRH Protein with 44 aminoacids Vazoactive intestinal polypeptide/ glukagon family
Human 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.
GH-releasing peptides (GHRP)or secretagogues (GHS) Ligands that increase GH produced by humans Do not use GHRH or SRIF receptors GHS-R G-protein associated rec protein kinase C hypothalamus, pituitary somatotrophs
Ghrelin Endogen ligand for GHS-R. Increase GH secretion in rats (intracellular Ca increase). Physiologic mediator of nutrition
GH effect Bound to GH-binding protein (GHBP) (at least 50 %) GHBP, is the extra cellular component of GH-R
GH-R member of cytokine rec family 620 aa protein On plasma membrane. Extracellular part is transport protein Single transmembrans helix Intracellular part
GH IGF’s (somatomedins) Similliar to proinsuline Effect on extrauterine growth via IGF-1ile (70aa polypeptide)
Fetal IGF-1 is correlated with gestastional age Newborn IGF-1 levels are % of adult values Increase through out childhood and reach adult levels in puberty Gonadal steroids increase IGF-1 production. In puberty levels are 2-3 fold higher than adult values Increase osteoblastic activity and collagen synthesis stimulate long bone growth
IGF’ s are bound to IGF binding proteins (IGFBP) t ½ Transport to target tissue. Modulate the relation with IGF rec 6 different IGFBP are cloned IGFBP-3, 90 % related to GH
Is derived from primitive pharynx-precursor of T4 producing cells And fourth pharengeal pouch- precursor of calcitonin(C) cells For development and descent of thyroid several transcription factors such asTITF1/NKX2, FOXE1 and PAX 8 are needed to work on time and coordinated Thyroid gland development
Embryogenesis After 1st month it is visable. At ıntrauterin 8 wk Tg synthesis begins shows thyroid activity 10. wk iodine trapping 12. wk colloid formation begins and withTSH sec from pituitary T4 synthesis begins This synthesis increase progresively with hypothalamic maturation after 18 wk of gestation
Tiroid kolloidi tiroglobulin Protein sentezi Çekirdek DNA/RNA sentezi Damar G proteini Thyroid hormone biosynthesis
Thyroid hormone synthesis Uptake I uptake actively with Na-iodine pump
Thyroid hormone synthesis Organification İyodine + thyroglobulin MIT DIT
Thyroid hormone synthesis Conjugation MIT + DIT T3 DIT +DITT4 Thyroid peroksidase(TPO)
TİROKSİN (T4) I HO I 1’ 2’ 3’ 4’ 5’6’ O I I CH 2 CH COOH NH 2 (fenol halkası)(tirozil halkası) b a I R O I I R I R O I I R 5’ - monodeyidinasyon5 - monodeyidinasyon Tip I-II monodeyiodinaz Tip III monodeyiodinaz T3 rT3
Iodine needs in different times of age Age and stages of life Daily idoine recommendation( g) 6 < months40 1< years in iodine deficient regions years Adoles and adults100 Pregnant and lactating women150
İYOT KLİRENSİ dolaşım I2I2 I2I2 I I %20 %80 Pasif reabsorbsiyon İdrarla iyot atılımı GFR + + I I ATPaz bağımlı Na-I simporter TSH (+) Follikül hücresi Daily iodine excretion gives intake
Iodine induced hyperthyoridism (Jodbasedow effect) Iodine induced hyperthyoridism (Jodbasedow effect) Nodular thyroid disease with otonomy and with out antibodies Diffuse goitre with thyroid stimulating antibodies Jodbasedow effect only in thyroids independent from TSH
Iodine deficiency Iodine deficiency disorders (IDD) global heath problem World’s most common endocrine disorder Most frequent reseason for goitre and hypothyroidism