Neuroendocrinologie Neuroendocrinologie Hipotalamusul Hipotalamusul Patologia vasopresinei Patologia vasopresinei Diabetul insipid Diabetul insipid Corin Badiu, 2013
Nov 08, 2015
Neuroimagistica seteiZece subiecti au efectuat PET-CT si o evaluare psihologica a setei (Denton, PNAS, 96, 5304-5309, 1999)
Oxytocin-like peptides 1 2 3 4 5 6 7 8 9Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly (NH2) Oxytocine * * * * * * * Ile * Mesotocine * * * Ser * * * Ile * Isotocine * * * Ser * * * Glu * Glumitocine * * * * * * * Val * Valitocine * * * Asn * * * * * Aspargtocine
Vasopressin-like peptides
1 2 3 4 5 6 7 8 9Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly (NH2) Vasopressine * * * * * * * Lis * Lisine-vasopressine
* Phe * * * * * * * Phenipressine
* * Ile * * * * * * Vasotocine
Structura hormonilor neurohipofizari
TM ITM IIITM IITM IVTM VTM VITM VIIReceptor V1a
Noyau paraventriculaire
Noyau supraoptique
Neurohypophyse de rat -ME
VasopresinaOxitocinaUterSinGonade? AH?AdipociteCreierSuprarenaleFicatAHMuschi netedRinichiHipotalamusCreier
SeteAVPSindroame poliuro-polidipsiceHipotalamus
Polidipsie psihogena
Absenta AVP
Vasopresinaza
Rinichi: rezistenta la AVPinsuficienta renala
IRM normalLechan RM. Neuroendocrinology of Pituitary Hormone Regulation. Endocrinology and Metabolism Clinics 16:475-501, 1987
Diabet insipid: Deficitul de AVPDeteriorarea hipotalamusului (site-ul de sinteza AVP), tijei pituitare (transportul AVP) sau a retrohipofizei (site-ul de stocare AVP), va duce la o boala cunoscut sub numele de diabet insipid central.Muli dintre aceti pacieni nu au hipersemnal in T1 in lobul posterior al hipofizei pe imagistica RMN a creierului.
Diabet InsipidCaracteristici clinice sunt rezultatul deficientei de AVP Excreia unor volume mari de urin (poliurie) Excreia de urin diluat (OSM
Hipernatremia Na+> 145 mEq/L Hipodipsie primara, DI (central sau nefrogen)
Diureza osmotica (DZ dezechilibrat)
Neurologic: astenie, stare confuzionala, convulsii, deficit focal.
Trat: Desmopresina 10 mg intranazal sau 0.12 mg x 3/zi slg (Minirin Melt)aport hidric po sau 5% glucoza: 1-2 L
Hiponatremia Neurologic: greata, edem cerebral, cefalee, obnubilare, coma
Semnele afectiunii de baza (Addison, hipopituitarism, SIADH)
Scadere Na+ hTaRapiditatea instalarii hNa+Na+ < 120 mEq/L: risc vital
Hiponatremia - tratamentEtiologicSIADH: Restrictie hidrica Antagonist Rec V2 AVP = Vaptan
Substitutie corticoida (HHC Fludrocortizon, 2 x 0.1 mg/zi)
Substitutie tiroidiana: LT4 in doze de la 25 la 100 mg/zi, sub protectie antiagreganta
Cresterea capitalului de Na: < 10-15 mEq / 24h
Solutii fiziologice sau saline hipertone 0.5 - 2 L/zi
Creste> 15mEq/zi Risc de mielinoza pontina (sdr de demielinizare osmotica), mai sever in hNa+ cronica
Reglarea i explorarea hipofizeiHipofiza: anatomie funcionalTipuri celulare i implicaii funcionaleComunicarea hipotalamo hipofizarAxa de cretere: reglare i explorare funcionalAxa tiroidian: reglare i explorare funcionalAxa suprarenal: reglare i explorare funcionalAxa gonadic: reglare i explorare funcional Explorarea: farmacologic / fiziologic ?
Concluzii
Cell types in pars distalis
Cell Type Secretory ProductsCell Population %Somatotroph Growth hormone 50Lactotroph Prolactin15Corticotroph Adrenocorticotropic hormone 15Thyrotroph Thyroid stimulating hormone10GonadotrophLuteinizing hormone-Follicle-stimulating hormone10
C-corticotroph: F -Folliculostellate cell; G-gonadotroph; L-Lactotroph; S-somatotroph, T -thyrotroph; UN-unknown.
Substances
Cell Types
Peptides:
Activin B, inhibin, follistatin
F, G
Aldosterone-stimulating factor
UN
Angiotensin II (angiotensinogen, angiotensin I-converting enzyme, cathepsin B, renin)
C,G,L, S
Atrial naturetic peptide
G
Corticotropin-releasing hormone-binding protein
C
Dynorphin
G
Galanin
L, S,T
GAWK (chromogranin B)
G
Growth hormone-releasing hormone
UN
Histidyl proline diketopiperazine
UN
Motilin
S
Neuromedin B
T
Neuromedin U
C
Neuropeptide Y
T
Neurotensin
UN
Protein 7B2
G, T
Somatostatin 28
UN
Substance P (Substance K)
G,L,T
Thyrotropin-releasing hormone
G, L,S,T
Vasoactive intestinal poltpeptide
G,L,T
Growth factors:
Basic fibroblast growth factor
C,F
Chondrocyte growth factor
UN
Epidermal growth factor
G,T
Insulin-like growth factor I
S,F
Nerve growth factor
UN
Pituitary cytotropic factor
UN
Transforming growth factor alpha
L,S,G
Vascular endothelial growth factor
F
Cytokines:
Interleukin-I beta
T
Interleukin-6
F
Leukemia inhibitory factor
C,F
Neurotransmitters:
Acetylcholine
C,L
Nitric oxide
F
Disorders of the Endocrine SystemExcess or deficiencyImpaired synthesisTransport and metabolism of hormonesResistance to hormone action
Reglarea Axei GH GHRH (44)SMS (14) GH IGF1 GHRP Ghrelin
Insulin Tolerance Test0.1/0.15 UI/Kgc, i.v.Obese: 0,3 UI/Kgc
Contraindicate Epileptic seizuresSevere heart ischemia
Oral Glucose Tolerance TestOral glucose 75gGH peak level> 1 mg/LAcromegaly: positive & differential diagnosis Diabetes Mellitus
IGF-1 : variation with age & sex
Reglarea Axei CSR CRH / VP ACTH Cortisol Leptina Citokine GR, CRHR, V1b, ACTH R,
Short ACTH Stimulation Test250 mg ACTH i.v.
Screening in Cushing Syndrome
Diagnosis in Cushing Syndrome
Inferior Petrosal Sinus SamplingV. femurala ... IPSCRH 100 ug i.v.Control - VCIIPS: -5, 0, 2, 5, 10 min
Reglarea Axei Tiroidiene TRH TSH T4 / T3 Type II deiodinase Leptina TR, TRH R, TSH R
TRH test400 mg i.v. TRHTSH is measured each 30 mins, for 3 h
Reglarea Axei Gonadice GnRH LH & FSH Prolactina Testosteron /E2, Pg Inhibina /activina
GnRH este eliberat in sistemulport hipotalamo- hipofizar, pornind din eminena median i legnd vascular adeno-hipofiza.
Eliberarea este pulsatil tonic, iniial nocturn, apoi i diurn, ulterior apare o descrcare major, pre-ovulatorie. Eliberarea tonic provine din MBA, cea pre-ovulatorie din AHPO
Controlul sintezei LH i FSH de ctre GnRh
Stage 1: Prepubertal, no pubic hair growthStage 2: Testes grow; scrotal skin becomes redder and coarser; sparse and fine hair develops at base of penisStage 3: Penis lengthens with small increase in diameter; scrotal skin reddens, thickens and crinkles, pubic hair thicker and coarserStage 4: Penis and testes continue to grow; pubic hair coarser, darker and more curlyStage 5: Penis at adult size; pubic hair covers symphysis pubis and extends to inner thighsStadiile dezvoltarii pubertare (Tanner)
Pulsatile LH Pattern in Human
Pulsatility in gonadal axis Pulsatile hormones: Mix & Measure
CONCLUZII Evaluarea bazala pentru hormonii cu secreie cvasiconstanta. Evaluare dinamica pentru hormoni cu ritm, sau secretie pulsatila. Teste de inhibiie pentru sindroame de hipersecretie. Teste de stimulare pentru deficit hormonal. Integrarea rezultatelor clinice, biochimice, imagistice. Tineti cont de : hormoni, transport, metaboliozare, receptori, interferente de reglare (feed-back nespecific).
*Slide Index CI0001L: A-F
DISCUSSION POINTS:
SLIDE BACKGROUND:Status as of March 2003.
**Regulation of food intakeThe regulation of food intake involves a complex interaction of systems that determine the size, content, and frequency of feedings. Presumably, the brain is the final processing center that translates central and peripheral signals to initiate or stop feeding. Neuronal circuits have been identified in the hypothalamus that affect satiation (level of fullness during a meal which regulates the amount of food consumed) and satiety (level of hunger after a meal is consumed which regulates the frequency of eating). Regulatory mechanisms also must be present that integrate determinants of short-term energy intake with long-term energy requirements.
The discovery of leptin, the protein product of the ob/ob gene, in 1995 [1] led to a marked increase in our understanding of the regulation of food intake. Leptin is produced by fat cells, released into the circulation, and it crosses the blood-brain barrier to bind to its receptor in the hypothalamus, which stimulates the expression of neuropeptides and neurotransmitters that inhibit food intake. Therefore, leptin provides a unique feedback signaling system that transmits information regarding adipose tissue energy stores to the central nervous system. Other peripheral organs also communicate with the brain about energy intake through neural signaling and endocrine pathways. The gastrointestinal system, which is responsible for digesting and absorbing ingested nutrients, is particularly involved. The gastrointestinal tract produces cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), apolipoprotein A-IV (apo A-IV), ghrelin, insulin, and glucose, which are likely involved in short-term, and possibly long-term, regulation of food intake. Central neuropeptides and neurotransmitter signals produced in hypothalamic nuclei stimulate 1) neuropeptide Y (NPY), 2) agouti-related protein (AGRP), 3) galanin, 4) orexin-A, and 5) dynorphin, or inhibit 1) a-melanocyte-stimulating hormone (a-MSH), a peptide derived from proopiomelanocortin (POMC), 2) corticotropin-releasing hormone/urocortin (CRH/UCN), 3) glucagon-like peptide-1 (GLP-1), 4) cocaine- and amphetamine-regulated transcript (CART), 5) norepinephrine (NE), and 5) serotonin (5-HT) [2]. There is a hierarchy in the relative importance, magnitude, and duration of each afferent input, and certain signals can override the effect of others. The redundancy of these complex signaling pathways tend to defend food intake and provides a formidable barrier to treating obesity. Therefore, a clear understanding of the factors involved in regulating food intake has important implications in designing therapeutic agents for obesity management.
Zhang Y, Proenca R, Maffei M, et al. Positional cloning of the mouse obese gene and its human homologue. Nature 1994;372:425-432.Schwartz MW, Woods SC, Porte D Jr, et al. Central nervous system control of food intake. Nature 2000;404:661-671. **Medical complication of obesity*****Source for drawing: http://www.ucihs.uci.edu/teachadolhealth/G&D.htm#Tanner stagingTanner staging system is based on 3 characteristics: a) size of testes, b) length of penis, and c) development of pubic hair. [See Marshall, W.A. & Tanner, J.M. (1970). Variations in the pattern of pubertal changes in boys. Archives of Disease in Childhood. 45, 13-23.]Published age ranges for each Tanner stage vary, but generallyStage 1: < 10 yearsStage 2: 10-13 yearsStage 3: 12-14 yearsStage 4: 13-15 yearsStage 5: 14-17 yearsRacial differences have been found in onset of puberty. In a recent study using NHANES III (Nutrition Examination Survey) data, African-American boys showed pubic hair growth earlier than White boys (nine months earlier) and earlier than Mexican-American boys (one year earlier). Pubic hair growth equalized at the end of the development process, with all three groups completing pubic hair growth phases within five months of each other. However, African-American boys started and completed genital development a year earlier than either of the other two groups studied. ( Herman-Giddens ME, Wang, L, & Koch, G. Secondary Sexual Characteristics in Boys. Archives of Pediatric Adolescent Medicine 2001;155:1022-1028.)Normal age of onset of puberty in boys ranges from age 9 to 17 yearsTesticular enlargement is the earliest sign of puberty in males Pubertal progression from sex maturity rating (Tanner) stage 2 to stage 5 can require 2.5 to 5 years to complete Gynecomastia commonly occurs in boys progressing through puberty