Identification of SPRED2 as a Novel Regulator of Hypothalamic-Pituitary-Adrenal Axis Activity and of Body Homeostasis: = SPRED2 - Ein neuer Regulator der Hypothalamus-Hypophysen-Nebennierenrindenachse und der Hormonbalance
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|---|---|
| Format: | Thesis Book |
| Language: | English |
| Published: |
Würzburg
2014
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| Subjects: | |
| Online Access: | Volltext Inhaltsverzeichnis |
| Physical Description: | 203 Seiten Illustrationen, Diagramme |
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| 100 | 1 | |a Ullrich, Melanie |e Verfasser |0 (DE-588)1112485805 |4 aut | |
| 245 | 1 | 0 | |a Identification of SPRED2 as a Novel Regulator of Hypothalamic-Pituitary-Adrenal Axis Activity and of Body Homeostasis |b = SPRED2 - Ein neuer Regulator der Hypothalamus-Hypophysen-Nebennierenrindenachse und der Hormonbalance |c vorgelegt von Melanie Ullrich aus Karlstadt |
| 246 | 1 | 1 | |a SPRED2 - Ein neuer Regulator der Hypothalamus-Hypophysen-Nebennierenrindenachse und der Hormonbalance |
| 264 | 1 | |a Würzburg |c 2014 | |
| 300 | |a 203 Seiten |b Illustrationen, Diagramme | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 502 | |b Dissertation |c Julius-Maximilians-Universität Würzburg |d 2014 | ||
| 546 | |a Zusammenfassung in deutscher und englischer Sprache | ||
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| 650 | 0 | 7 | |a Hypophysen-Zwischenhirn-System |0 (DE-588)4161134-2 |2 gnd |9 rswk-swf |
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| _version_ | 1804176542162485248 |
|---|---|
| adam_text | ID E N TIFIC A TIO N O F SPRED2 AS A N OVEL R EGULATOR O F
H Y P O TH A LA M IC -P ITU ITA RY .A D RE N A L AXIS A C TIV ITY AND O
F
BODY HOM EOSTASIS
DISSERTATION ZUR ERLANGUNG DES
NATURWISSENSCHAFTLICH DOKTORGRADES
DER JULIUS-MAXIMILIANS-UNIVERSITAET WUERZBURG
VORGELEGT VON
MELANIE ULLRICH
AUS KARLSTADT
WUERZBURG 2014
TABLE OF CONTENTS
SUMMARY 1
..........................................................................................
1
ZUSAMMENFASSUNG 2
......................................................................3
INTRODUCTION 3
...................................................................................5
3.1 **** SIGNALING - CONTROL OF PROLIFERATION AND GROWTH
*************************5
3.1.1 THE RAS/ERK/****
PATHWAY...........................................................................................
5
3.1.2. RAS/ERK/**** PATHWAY DYSREGULATION - CAUSES OF CANCER AND
RASOPATHIES
.....................................
8
3.2. SPREDS - INHIBITORS OF THE RAS/ERK/**** PATHWAY
..............................................................................
9
3.2.1. SPRED
ISOFORMS....................................................................................................................................................9
3.2.2. SPRED DOMAIN STRUCTURE AND
FUNCTIONS.....................................................................................................10
3.2.2.1THE EVHL
DOMAIN.........................................................................................................................................................................................10
3.2.2.2 THE *-KIT BINDING D
0
MA*N
...........................................................................................................................................................................11
3.2.2.3. THE SPROUTY
DOMAIN...................................................................................................................................................................................
11
3.2.3. SPRED EXPRESSION PATTERNS AND
LOCALIZATIONS............................................................................................12
3.2.4. SPREDS AND SUPPRESSION OF RAS/ERK/****
SIGNALING.............................................................................
14
3.2.5. REGULATION OF SPRED-MEDIATED RAS/ERK/**** PATHWAY INHIBITION
......................................................
15
3.2.6 SPRED FUNCTIONS IN MICE AND M EN
................................................................
..............................................
17
32.6.1 IN VITRO STUDIES AND MOUSE
MODELS.........................................................................................................................................................17
3.2.6.2. FIRST LESSONS ^OM
HUMANS......................................................................................................................................................................
22
3.3 THE MOUSE - A RESEARCH MODEL FOR HUMAN GENE FUNCTION AND DISEASE
...........................................
24
3.3.1 MUTAGENESIS STRATEGIES IN M IC E
.....................................................................................................................
25
3 3 .2 . GENE TRAPPING * KNOCKOUT ON THE FAST
LANE..............................................................................................
27
3.4. HORMONAL REGULATION OF BODY
HOMEOSTASIS.........................................................................................29
3.4.1. THE HYPOTHALAMIC-PITUITARY-ADRENAL
AXIS....................................................................................................
29
3.4.1.1. THE HYPOTHALAMUS - NEURAL STIMULI TRIGGER THE RELEASE OF CRH
AND
AVP...................................................................................30
3.4.1.2. THE PITUITARY - CRH/AVP-MED*ATED ACTH RELEASE FROM ANTERIOR
LOBE ARID OSMOLALITY/VOLUME-MEDIATED AVP RELEASE
FROM POSTERIOR
LOBE.................................................................................................................................................................................................
32
3.4.1.3. THE ADRENAL
*
ACTH REGULATES THE RELEASE OF GLUCOCORTICOIDS AND
MINERALOCORTICOIDS...................................................*.
34
3.4.1.4. FEEDBACK REGULATION AND CIRCADIAN RHYTHM OF THE HPA
AX*S....................................................................................
.
37
3.4.2 THE RENIN-ANGIOTENSIN.ALDOSTERONE
AXIS.....................................................................................................38
3.4.2.1. THE RENIN-ANGIOTENSIN SYSTEM
(RAS)....................................................................................................................................................
38
3.4.2.2.
ALDOSTERONE........................................................................................................................................................
.
40
3.4.2.3. RAS FEEDBACK REGULATION, DYSREGULATION, ANTAGONISTS, AND
ASSOCIATED
DISEASES.......................................................................42
35 AIM OF
THESIS................................................................................................................................................43
MATERIALS AND METHODS 4 ******************************47
4.1 MOUSE
HANDLING..........................................................................................................................................47
4.1.1 GENERATION OFSPRED2
**
MICE......................................................................................................................47
4.1.2 MOUSE RAISING AND
BREEDING.......................................................................................................
47
4.1.3 GENOTYPING OF SPRED2-DEF*C*ENT M IC E
.........................................................................................................
48
4.2 MOUSE
EXPERIMENTS....................................................................................................................................
49
4.2.1 EXAMINATION OF W ATER
UPTAKE........................................................................................................................
50
4.2.2 EXPERIMENTAL W ATER
DEPRIVATION...................................................................................................................
50
4.2.3. BLOOD COLLECTION AND SERUM
PREPARATION.....................................................................................................50
4.2.4 DETERMINATION OF ROUTINE LABORATORY SERUM PARAMETERS
.......................................................................
51
4.2.5. DETERMINATION OF HORMONE
LEVELS......................................................... 51
4.2.6 WOUND CONTROL AND
MONITORING.....................................................................................................................52
4.3. CLONING OF CDNAS AND EXPRESSION
PLASMIDS.........................................................................................
52
4 .3 1 . PCDNA3.1*EVHL*SS*GEO AND PCDNA3
*
L-SS -G EO
..............................................................................................
52
4.3.2 PGL3*CRHPR
*
M-REAND PGL3*CRHP
*
*
M...................................................................................................
.. 54
4.4. CELL CULTURE, TRANSFECTION, AND IN VITRO
ASSAYS.......................................................................................
55
4.4.1 CULTIVATION OF HEK 293 T
CELLS.........................................................................................................................
55
4.4.2 CULTIVATION OF MHYPOE44*
CELLS......................................................................................................................56
4.4.3 TRANSFECTION OF HEK 293 T AND MHYPOE44*
CELLS.......................................................................................
56
4.4.4
IN VITRO
ERK ACTIVITY
ASSAY...............................................................................................................................57
4.4.5
IN VITRO
CRH PROMOTER REPORTER
ASSAY.....................................................................................................
57
4.4.6
IN VITRO
ETS TRANSCRIPTION FACTOR REPORTER
ASSAY........................................................................................
58
4.5. ANALYSIS AND QUANTIFICATION OF PROTEIN AND MRNA
EXPRESSION............................................................
58
4.5.1. WESTERN
*
1
*
1............
**
....
**
......
*
....
*
.
*
**
...
***
.....
*
*
...
*
.
**
......
*
..............
*
..............
*
..............
*
......^ 58
4.5.2 NORTHERN
BLOT.....................................................................................................................................................
60
4.5.3. QUANTIFICATION OF ERK PHOSPHORYLATION AND OF CRH MRNA LEVELS *N
BRAIN
........................................
61
4.6. HISTOLOGY AND
IMMUNOHISTOCHEMISTRY.................................................................................................
62
4.6.1 HEMATOXYLIN AND EOSIN STAINING (*&*
STAINING)..........................................................................................
62
4.6.2 TUNEL
ASSAY.......................................................................................................................................................
62
4.6.3.
IMMUNOHISTOCHEMISTRY....................................................................................................................................63
4.6.4 X*GAL
STAINING.....................................................................................................................................................63
4.7
STATISTICS........................................................................................................................................................64
4.7.1. BASIC
STATISTICS....................................................................................................................................................64
4.7.2 KAPLAN-MEIER SURVIVAL
ANALYSIS......................................................................................................................
64
RESULTS 5 *******************************67
5.1 GENERATION OF SPRED2 ** M IC E
................................................................................................................
67
5.2 BREEDING AND GENOTYPING OF SPRED2 ** M IC E
......................................................................................
69
5.3. THE EVHL*SS-GE* FUSION PROTEIN EXPRESSED *N SPRED2 ** MICE MAY ACT
DOMINANT NEGATIVE. .. .70
5.3.1. DELETION OFSPRED2 BUT EXPRESSION OF AN EV H L-SS-GE. FUSION
PROTEIN.................................................71
5.3.2 FUNCTIONAL EXPRESSION OF SUBCLONED EVHL*SS-GE
0
*N EUKARYOTIC
CELLS.....................................................72
5.3.3 PUTATIVE DOMINANT NEGATIVE EFFECT OF EVHL-SS-GE
0
ON SPREDL AND RAS/ERK/**** SIGNALING IN
SPRED2 KO M
ICE............................................................................................................................................................74
5.4. OBVIOUS AND VERSATILE PHENOTYPE IN SPRED2 ** MICE
*************************75
5.5. SPRED2 DEFICIENCY IN MICE LEADS TO HYDRONEPHROSIS RENAL ATROPHY,
AND KIDNEY DETERIORATION **75
5.6. HYDRONEPHROSIS IS ASSOCIATED WITH TUBULAR BREAKDOWN AND APOPTOSIS
IN SPRED2 ** MICE *******77
5.7. KIDNEY DAMAGE *N SPRED2 KOS IS ACCOMPANIED BY POLYDIPSIA,
HYPEROSMOLALITY, AND HIGHER SERUM
SALT 1*
*
*......
*
**
*
.
*
._....
*
.
**
.
*
...........
*
.
**
.
*
........
*
....
*
*
_
*.
*
...........*.
*
......*
*
*.^
5.8. SERUM PARAMETER ANALYSES UNDERLINE KIDNEY DAMAGE AND INDICATE
SPRED2 DEFICIENCY-PROVOKED
HOMEOSTATIC
IMBALANCE......................................................................................................................................80
5.9. LOSS OF SPRED2 LEADS TO DYSREGULATION OF SALT AND WATER
HOMEOSTASIS-CONTROLLING HORMONES . 8 3 .*
5.9.1 AUGMENTED ALDOSTERONE SECRETION IS ACCOMPANIED BY ELEVATED
EXPRESSION OF ALDOSTERONE-
SYNTHASE.........................................................................................................................................................................
83
5.9.2. HYPERALDOSTERONISM DEVELOPS INDEPENDENTLY OF REN*N-ANG*OTENS*N
SYSTEM ACTIVITY ....... 84
5.9.3. W ATER DEPRIVATION CAUSES ELEVATED LOSS OF BODY FLUID IN SPRED2 *
* MICE ..... 85
5.9.4 VASOPRESSIN RESPONSE IS UNAFFECTED BY ABLATION OF
SPRED2....................................................................88
5.10* INCREASED RELEASE OF THE STRESS HORMONES CRH, ACTH, AND
CORTICOSTERONE FROM THE
HYPOTHALAMIC-PITUITARY-ADRENAL AXIS *N SPRED2
**
MICE...........................................................................
89
5.11. AUGMENTED HYPOTHALAM*C-P*TU*TARY-ADRENAL STRESS HORMONE RELEASE IS
ACCOMPANIED BY
ELEVATED HYPOTHALAMIC-PITUITARY GROWTH HORMONE SECRETION *N SPRED2
**
MICE..............................90
5.12. OVERSHOOTING STRESS HORMONE RELEASE IS ASSOCIATED WITH OBSESSIVE
GROOMING AND SELF-INFLICTED
SKIN LES*ONS )N SPRED2
**
MICE.......................................................................................................................S
I
5.13. SPRED2 EXPRESSION PROFILING *N HYPOTHALAMIC-PITUITARY-ADRENAL
TISSUES AND KIDNEY ****************93
5.14. SPRED2 INHIBITS HYPOTHALAMIC CRH PRODUCTION AND RELEASE BY
DOWNREGULATING CRH PROMOTER
ACTIVITY *N AN ERK/MAPK/ETSL.DEPENDENT M
ANNER......................................................................................95
5.14.1. INCREASED
IN VIVO
ERK PHOSPHORYLATION IN BRAINS OF SPRED2
KOS...................................................... 95
5.14.2 SPREDS SUPPRESS CRH TRANSCRIPTION
IN VITRO
............................................................................................96
5.14.3. SPREDS INHIBITORY EFFECT ON CRH PROMOTER ACTIVITY S DEPENDENT
ON ERK/MAPK-MED*ATED
REGULATION OF ETS TRANSCRIPTION
FACTORS...................................................................................................................
98
5.14.4. SPREDS REDUCED CRH RELEASE FROM MHYPOE44* CELLS
IN VITRO
............................................................99
5.14.5 HIGHER CONTENT OF CRH MRNA IN HYPOTHALAMIC PVN-CONTAINING BRAIN
REGIONS OF SPRED2-DEF*C*ENT
M ICE
...............................................................................................................................................................................LOO
5.15.
REDUCED SURVIVAL PROBABILITY *N SPRED2
**
MICE..............................................................................
101
DISCUSSION 6
....................................................................................
103
6.1. THE SPRED2 GENE TRAP MODEL - POSSIBLE EFFECTS OF THE EVHL-SS-GE.
FUSION PROTEIN .. 103
6.2.
CAUSES OF KIDNEY DAMAGE *N SPRED2
**
MICE - AN INTERPLAY OF HYDRONEPHROSIS ATROPHY, AND
APOPTOSIS...........................................................................................................................................................
1 .6
6.3. POLYDIPSIA, IMPAIRED WATER RETENTION, AND HYPEROSMOLALITY ** SPRED2
KOS - NO EFFECT OF SPRED2
ON AVP-DEPENDENT WATER BALANCE
REGULATION............................................................................................108
6.4. HYPERALDOSTERONSIM - THE ELICITOR OF HYPEROSMOLALITY AND SALT AND
WATER IMBALANCES *N SPRED2
KO M ITE
.............................................................................................................................................................
109
6.5. INCREASED ALDOSTERONE-SYNTHASE EXPRESSION AND ELEVATED SERUM ACTH -
CAUSES OF REN*N-
ANGIOTENSIN SYSTEM-INDEPENDENT
HYPERALDOSTERONISM.............................................................................
110
6.6 HYPERACTIVITY OF THE HPA AXIS IN SPRED2*DEFIC)ENT MICE - ELEVATED
RELEASE OF STRESS AND GROWTH
HORMONES..........................................................................................................................................................
113
6.7 EXCESSIVE GROOMING *N SPRED2 KOS - A RESULT OF HPA AXIS
OVERACTIVITY AND EVIDENCE OF
ENDOGENOUS
STRESS...........................................................................................................................................
115
6.8. SPRED2 - A NOVEL REGULATOR OF CRH GENE TRANSCRIPTION AND
RELEASE................................................116
6.9. SPREDL AND SPRED2 DEFICIENCY - REDUDANCY IN PROTEIN FUNCTION AND
IMPACT ON CANCER AND
RASOPATHIES.......................................................................................................................................................118
CONCLUSION AND OUTLOOK 7 123
7.1. SPRED2 * A CRITICAL MEDIATOR OF SYNAPTIC TRANSMISSION AND REGULATOR
OF BEHAVIOR? 125
7.2. SPRED2 - A NOVEL REGULATOR OF CARDIAC HYPERTROPHY AND ELECTRICAL
CONDUCTION *N THE HEART?....126
7.3. SPRED2 DEFICIENCY - A CAUSE OF RASOPATHY *N HUMANS?
....................................................................
128
REFERENCES 8
..................................................................................131
APPENDIX
*
...................................................................................
157
9.1 .
GENOTYPING................................................................................................................................................
157
9.2. EVHL-SS-GE. FUSION
PROTEIN......................................................................................................................165
9.3. CRH PROMOTER REPORTER
ASSAY................................................................................................................
168
9.4 VECTOR
CARDS...............................................................................................................................................173
9.5 4XETSL REPORTER
ASSAY..............................................................................................................................178
9.6 TRANSCRIPTION FACTOR BINDING SITE PREDICTION IN THE MURINE CRH
PROMOTER
.....................................
181
9.7 NORTHERN
BLOT.............................................................................................................................................195
9.8.
ABBREVIATIONS.............................................................................................................................................197
|
| any_adam_object | 1 |
| author | Ullrich, Melanie |
| author_GND | (DE-588)1112485805 |
| author_facet | Ullrich, Melanie |
| author_role | aut |
| author_sort | Ullrich, Melanie |
| author_variant | m u mu |
| building | Verbundindex |
| bvnumber | BV043740753 |
| collection | ebook |
| ctrlnum | (OCoLC)958050742 (DE-599)BVBBV043740753 |
| dewey-full | 610 |
| dewey-hundreds | 600 - Technology (Applied sciences) |
| dewey-ones | 610 - Medicine and health |
| dewey-raw | 610 |
| dewey-search | 610 |
| dewey-sort | 3610 |
| dewey-tens | 610 - Medicine and health |
| discipline | Medizin |
| format | Thesis Book |
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| genre | (DE-588)4113937-9 Hochschulschrift gnd-content |
| genre_facet | Hochschulschrift |
| id | DE-604.BV043740753 |
| illustrated | Illustrated |
| indexdate | 2024-07-10T07:33:50Z |
| institution | BVB |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-029152487 |
| oclc_num | 958050742 |
| open_access_boolean | 1 |
| owner | DE-384 DE-473 DE-BY-UBG DE-703 DE-1051 DE-824 DE-29 DE-12 DE-91 DE-BY-TUM DE-19 DE-BY-UBM DE-1049 DE-92 DE-739 DE-898 DE-BY-UBR DE-355 DE-BY-UBR DE-706 DE-20 DE-1102 |
| owner_facet | DE-384 DE-473 DE-BY-UBG DE-703 DE-1051 DE-824 DE-29 DE-12 DE-91 DE-BY-TUM DE-19 DE-BY-UBM DE-1049 DE-92 DE-739 DE-898 DE-BY-UBR DE-355 DE-BY-UBR DE-706 DE-20 DE-1102 |
| physical | 203 Seiten Illustrationen, Diagramme |
| psigel | ebook |
| publishDate | 2014 |
| publishDateSearch | 2014 |
| publishDateSort | 2014 |
| record_format | marc |
| spelling | Ullrich, Melanie Verfasser (DE-588)1112485805 aut Identification of SPRED2 as a Novel Regulator of Hypothalamic-Pituitary-Adrenal Axis Activity and of Body Homeostasis = SPRED2 - Ein neuer Regulator der Hypothalamus-Hypophysen-Nebennierenrindenachse und der Hormonbalance vorgelegt von Melanie Ullrich aus Karlstadt SPRED2 - Ein neuer Regulator der Hypothalamus-Hypophysen-Nebennierenrindenachse und der Hormonbalance Würzburg 2014 203 Seiten Illustrationen, Diagramme txt rdacontent n rdamedia nc rdacarrier Dissertation Julius-Maximilians-Universität Würzburg 2014 Zusammenfassung in deutscher und englischer Sprache Knockout Molekulargenetik (DE-588)4671699-3 gnd rswk-swf Renin-Angiotensin-System (DE-588)4177770-0 gnd rswk-swf Spred-Proteine (DE-588)7549382-2 gnd rswk-swf MAP-Kinase (DE-588)4576144-9 gnd rswk-swf Hypophysen-Zwischenhirn-System (DE-588)4161134-2 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Renin-Angiotensin-System (DE-588)4177770-0 s Spred-Proteine (DE-588)7549382-2 s MAP-Kinase (DE-588)4576144-9 s Hypophysen-Zwischenhirn-System (DE-588)4161134-2 s Knockout Molekulargenetik (DE-588)4671699-3 s DE-604 Erscheint auch als Online-Ausgabe urn:nbn:de:bvb:20-opus-107355 https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-107355 Resolving-System kostenfrei Volltext DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029152487&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Ullrich, Melanie Identification of SPRED2 as a Novel Regulator of Hypothalamic-Pituitary-Adrenal Axis Activity and of Body Homeostasis = SPRED2 - Ein neuer Regulator der Hypothalamus-Hypophysen-Nebennierenrindenachse und der Hormonbalance Knockout Molekulargenetik (DE-588)4671699-3 gnd Renin-Angiotensin-System (DE-588)4177770-0 gnd Spred-Proteine (DE-588)7549382-2 gnd MAP-Kinase (DE-588)4576144-9 gnd Hypophysen-Zwischenhirn-System (DE-588)4161134-2 gnd |
| subject_GND | (DE-588)4671699-3 (DE-588)4177770-0 (DE-588)7549382-2 (DE-588)4576144-9 (DE-588)4161134-2 (DE-588)4113937-9 |
| title | Identification of SPRED2 as a Novel Regulator of Hypothalamic-Pituitary-Adrenal Axis Activity and of Body Homeostasis = SPRED2 - Ein neuer Regulator der Hypothalamus-Hypophysen-Nebennierenrindenachse und der Hormonbalance |
| title_alt | SPRED2 - Ein neuer Regulator der Hypothalamus-Hypophysen-Nebennierenrindenachse und der Hormonbalance |
| title_auth | Identification of SPRED2 as a Novel Regulator of Hypothalamic-Pituitary-Adrenal Axis Activity and of Body Homeostasis = SPRED2 - Ein neuer Regulator der Hypothalamus-Hypophysen-Nebennierenrindenachse und der Hormonbalance |
| title_exact_search | Identification of SPRED2 as a Novel Regulator of Hypothalamic-Pituitary-Adrenal Axis Activity and of Body Homeostasis = SPRED2 - Ein neuer Regulator der Hypothalamus-Hypophysen-Nebennierenrindenachse und der Hormonbalance |
| title_full | Identification of SPRED2 as a Novel Regulator of Hypothalamic-Pituitary-Adrenal Axis Activity and of Body Homeostasis = SPRED2 - Ein neuer Regulator der Hypothalamus-Hypophysen-Nebennierenrindenachse und der Hormonbalance vorgelegt von Melanie Ullrich aus Karlstadt |
| title_fullStr | Identification of SPRED2 as a Novel Regulator of Hypothalamic-Pituitary-Adrenal Axis Activity and of Body Homeostasis = SPRED2 - Ein neuer Regulator der Hypothalamus-Hypophysen-Nebennierenrindenachse und der Hormonbalance vorgelegt von Melanie Ullrich aus Karlstadt |
| title_full_unstemmed | Identification of SPRED2 as a Novel Regulator of Hypothalamic-Pituitary-Adrenal Axis Activity and of Body Homeostasis = SPRED2 - Ein neuer Regulator der Hypothalamus-Hypophysen-Nebennierenrindenachse und der Hormonbalance vorgelegt von Melanie Ullrich aus Karlstadt |
| title_short | Identification of SPRED2 as a Novel Regulator of Hypothalamic-Pituitary-Adrenal Axis Activity and of Body Homeostasis |
| title_sort | identification of spred2 as a novel regulator of hypothalamic pituitary adrenal axis activity and of body homeostasis spred2 ein neuer regulator der hypothalamus hypophysen nebennierenrindenachse und der hormonbalance |
| title_sub | = SPRED2 - Ein neuer Regulator der Hypothalamus-Hypophysen-Nebennierenrindenachse und der Hormonbalance |
| topic | Knockout Molekulargenetik (DE-588)4671699-3 gnd Renin-Angiotensin-System (DE-588)4177770-0 gnd Spred-Proteine (DE-588)7549382-2 gnd MAP-Kinase (DE-588)4576144-9 gnd Hypophysen-Zwischenhirn-System (DE-588)4161134-2 gnd |
| topic_facet | Knockout Molekulargenetik Renin-Angiotensin-System Spred-Proteine MAP-Kinase Hypophysen-Zwischenhirn-System Hochschulschrift |
| url | https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-107355 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029152487&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT ullrichmelanie identificationofspred2asanovelregulatorofhypothalamicpituitaryadrenalaxisactivityandofbodyhomeostasisspred2einneuerregulatorderhypothalamushypophysennebennierenrindenachseundderhormonbalance AT ullrichmelanie spred2einneuerregulatorderhypothalamushypophysennebennierenrindenachseundderhormonbalance |