PMID- 19325006
OWN - NLM
STAT- MEDLINE
DCOM- 20090724
LR  - 20211020
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 150
IP  - 7
DP  - 2009 Jul
TI  - The differences in neuroprotective efficacy of progesterone and 
      medroxyprogesterone acetate correlate with their effects on brain-derived 
      neurotrophic factor expression.
PG  - 3162-8
LID - 10.1210/en.2008-1247 [doi]
AB  - Whereas hormone therapy is used for the treatment of menopausal symptoms, its 
      efficacy in helping reduce the risk of other diseases such as Alzheimer's disease 
      has been questioned in view of the results of recent clinical trials that 
      appeared inconsistent with numerous basic research studies that supported the 
      beneficial effects of hormones. One possible explanation of this discrepancy may 
      lie in the choice of hormone used. For example, we and others found that 
      progesterone is neuroprotective whereas medroxyprogesterone acetate (MPA), the 
      synthetic progestin used in hormone therapy, is not. Because our data suggest 
      that progesterone-induced protection is associated with the induction of 
      brain-derived neurotrophic factor (BDNF) levels and, importantly, can be blocked 
      by inhibiting the neurotrophin signaling, we determined whether progesterone and 
      medroxyprogesterone acetate differed in their ability to regulate BDNF levels in 
      the explants of the cerebral cortex. We found that progesterone elicited an 
      increase in both BDNF mRNA and protein levels, whereas medroxyprogesterone 
      acetate did not. Furthermore, using both a pharmacological inhibitor of the 
      progesterone receptor (PR) and PR knockout mice, we determined that the effects 
      of progesterone were mediated by the classical PR. Our results underscore the 
      fact that not all progestins have equivalent effects on the brain and suggest 
      that the selection of the appropriate progestin may influence the success of 
      hormone therapy formulations used in treating the menopause and/or reducing the 
      risk for diseases associated with the postmenopausal period.
FAU - Jodhka, Parmeet K
AU  - Jodhka PK
AD  - Department of Pharmacology and Neuroscience, University of North Texas Health 
      Science Center at Fort Worth, 3400 Camp Bowie Boulevard, Fort Worth, Texas 
      76107-2699, USA.
FAU - Kaur, Paramjit
AU  - Kaur P
FAU - Underwood, Wendy
AU  - Underwood W
FAU - Lydon, John P
AU  - Lydon JP
FAU - Singh, Meharvan
AU  - Singh M
LA  - eng
GR  - P01 AG022550/AG/NIA NIH HHS/United States
GR  - P01 AG027956/AG/NIA NIH HHS/United States
GR  - R03 AG023330/AG/NIA NIH HHS/United States
GR  - AG022550/AG/NIA NIH HHS/United States
GR  - AG023330/AG/NIA NIH HHS/United States
GR  - AG027956/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090326
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Progesterone)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - C2QI4IOI2G (Medroxyprogesterone Acetate)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis/drug effects
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Glutamic Acid/toxicity
MH  - Medroxyprogesterone Acetate/*pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Progesterone/*pharmacology
MH  - RNA, Messenger/metabolism
MH  - Receptors, Progesterone/drug effects/*physiology
PMC - PMC2703540
EDAT- 2009/03/28 09:00
MHDA- 2009/07/25 09:00
PMCR- 2010/07/01
CRDT- 2009/03/28 09:00
PHST- 2009/03/28 09:00 [entrez]
PHST- 2009/03/28 09:00 [pubmed]
PHST- 2009/07/25 09:00 [medline]
PHST- 2010/07/01 00:00 [pmc-release]
AID - en.2008-1247 [pii]
AID - 4836 [pii]
AID - 10.1210/en.2008-1247 [doi]
PST - ppublish
SO  - Endocrinology. 2009 Jul;150(7):3162-8. doi: 10.1210/en.2008-1247. Epub 2009 Mar 
      26.