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
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
