Development of Complex Curricula for Molecular Bionics and Infobionics Programs within a consortial* framework**
Consortium leader
PETER PAZMANY CATHOLIC UNIVERSITY
Consortium members
SEMMELWEIS UNIVERSITY, DIALOG CAMPUS PUBLISHER
The Project has been realised with the support of the European Union and has been co-financed by the European Social Fund ***
**Molekuláris bionika és Infobionika Szakok tananyagának komplex fejlesztése konzorciumi keretben
***A projekt az Európai Unió támogatásával, az Európai Szociális Alap társfinanszírozásával valósul meg.
CATHOLIC UNIVERSITY UNIVERSITY
Faculty of Information Technology
BEVEZETÉS A FUNKCIONÁLIS NEUROBIOLÓGIÁBA
INTRODUCTION TO FUNCTIONAL NEUROBIOLOGY
STEROID FEEDBACK TO THE BRAIN
www.itk.ppke.hu
Steroid feedback to the brain
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COMMUNICATION
SYNAPTIC
NON-SYNAPTIC HUMORAL
Steroid feedback to the brain
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THYROID GLAND ADRENAL GLAND
GONADS
Steroid feedback to the brain
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SYNTHESIS
Progesterone
17OH-pregnenolone
Androstene-3,17-dione Dehydroepiandrosterone
17OH-progesterone
11-deoxycorticosterone 11-deoxycortisol
Cortisol Corticosterone
Aldosterone Pregnenolone
Steroid feedback to the brain
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Steroid feedback to the brain
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Mineralocorticoid receptor
mRNA Glucocorticoid receptor
mRNA
Corticosterone: 1 ligand, 2 receptors
in vivo in situ
autoradiography hybridization
3H-DEX 0
50 100
Receptor saturation (%)
Corticosterone
3H-ALDO MR
GR
Courtesy of Dr. O. Almeida
Steroid feedback to the brain
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FM
EM
HIPPOCAMPUS
GD
A
D
X
Steroid feedback to the brain
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Receptor: ligand dependent transcription factor Nuclear receptor superfamily
R
mRNADNAL
coregulator - /+
R
Steroid feedback to the brain
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E S T R O G E N S
SERM
1.
2.
3. 4.
5.
Steroid feedback to the brain
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Gametogenesis Sexual phenotype Ovarian cycle Sexual behavior Bone metabolism
Cardiovascular system Cognitive functions Synaptic plasticity
Cell proliferation in breast and uterus
T E
Steroid feedback to the brain
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Steroid feedback to the brain
www.itk.ppke.hu
Transactivation
N C
A/B C D E F
Modulator DNA-binding Ligand-binding
AF1 AF2
Transcription
Dimerization Hsp
Functional structure of steroid receptors
Steroid feedback to the brain
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Characteristics of estrogen receptor knock out (ERKO) female mice
Gametogenesis
Estrogen level
Breast Ovary Uterus
suppressed
elevated agenesis abnormal follicles
infantile
ERKO 3 H-E 2
Steroid feedback to the brain
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Proc. Natl. Acad. Sci. USA: Vol. 93, No. 12, 5925 5930, June 11, 1996
Cloning of a Novel Estrogen Receptor Expressed in Rat Prostate and Ovary
GGJM Kuiper, E Enmark, M Pelto-Huikko, S Nilsson, and J Gustafsson
A/B C D E F
25 95 30 60 20
α β
DNA LBD
Steroid feedback to the brain
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ER-β LBD crystal structure
ER actions
1 2 3 4
Steroid feedback to the brain
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α
β α β
HOMODIMER
HETERODIMER
ER α and ER β distribution in brain
Forrás: Shughrue, P. et al., J. Comp. Neurology
ER α ER β
Steroid feedback to the brain
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Steroid feedback to the brain
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OCH
OCH
VASOPRESSIN
ERβ
OCH
VASOPRESSIN-ERβ
Steroid feedback to the brain
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OXY - ir
ERβ
Steroid feedback to the brain
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Projections of LHRH neurons
HYPOPHYSIS
Steroid feedback to the brain
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E 2
Steroid feedback to the brain
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0 X
LHRH E
2?
HYPOTHALAMUS
OVULATION
OVARY HYPOPHYSIS
Steroid feedback to the brain
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INDIRECT REGULATION
Steroid feedback to the brain
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Steroid feedback to the brain
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RAT
Human
Ethical permit: No. 372
Steroid feedback to the brain
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Time (hours)
LH (ng/ml)
0 1 2 3 4 5 6 7
Time (hours)
LH (ng/ml)
0 1 2 3 4 5 6
7 Mepyramine (100 nmol/hr; n=7)
Saline (n=6)
14.00 16.00 18.00 20.00 22.00 00.00 02.00 12.00
ICV Infusion
14.00 16.00 18.00 20.00 22.00 00.00 02.00 12.00
ICV Infusion
† †
†
† †
Ranitidine (100 nmol/hr; n=5) Saline (n=4)
†
*
*
*
†
H1
H2
Effects of H receptor antagonists on LH release
MEPYRAMINE
RANITIDINE
Steroid feedback to the brain
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E
KÖZVETLEN?
LHRH mRNA
Double ISH
Steroid feedback to the brain
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Steroid feedback to the brain
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20 30 40 50 60 70 80
OVX OVX+E2 OVX MALE ER-βmRNS EXPRESSZIÓ LHRH SEJTEKBEN
%
ERβ protein expression in LHRH neurons
Steroid feedback to the brain
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GABA Histamine
E 2
ERβ
ERα
LHRH neuron
ERβ
Indirect, trans-synaptic effect
Direct, genomic effect
Fast, membrane effect
Steroid feedback to the brain
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BIOLOGY
PHARMACOLOGY
CHEMISTRY
MULTIDISCIPLINARY RESEARCH
