PMID- 17510244
OWN - NLM
STAT- MEDLINE
DCOM- 20070911
LR  - 20211203
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 148
IP  - 8
DP  - 2007 Aug
TI  - Follicle-stimulating hormone increases tuberin phosphorylation and mammalian 
      target of rapamycin signaling through an extracellular signal-regulated 
      kinase-dependent pathway in rat granulosa cells.
PG  - 3950-7
AB  - FSH-mediated regulation of mammalian target of rapamycin (mTOR) signaling in 
      proliferating granulosa cells and the effect of dihydrotestosterone (DHT) on this 
      pathway were examined. Inhibiting mTOR activation using rapamycin significantly 
      reduced the FSH-mediated increase in cyclin D2 mRNA expression, suggesting that 
      mTOR plays a role in the FSH-mediated increase in granulosa cell proliferation. 
      FSH treatment of granulosa cells showed a 2-fold increase in phosphorylation of 
      p70S6 kinase (p70S6K), the downstream target of mTOR. The increase in p70S6K 
      phosphorylation by FSH treatment was abolished by prior exposure to DHT, 
      suggesting that DHT inhibits FSH-mediated activation of mTOR signaling in 
      cultured granulosa cells. The effect of FSH and DHT treatment on tuberin (TSC2), 
      the upstream regulator of mTOR, was then examined. FSH treatment increased TSC2 
      phosphorylation, and pretreatment with DHT for 24 h reduced this stimulation. 
      These results indicate that reduced p70S6K phosphorylation observed in 
      DHT-treated cells might be the result of reduced TSC2 phosphorylation. Because 
      Akt is the upstream activator of TSC2 phosphorylation, the effect of Akt 
      inhibition was examined to test whether FSH-mediated TSC2 phosphorylation 
      proceeds through an Akt-dependent pathway. Our results show that inhibiting Akt 
      phosphorylation did not block FSH-stimulated TSC2 phosphorylation, whereas ERK 
      inhibition reduced FSH-mediated stimulation. These results demonstrate the 
      involvement of ERK rather than Akt in FSH-mediated TSC2 phosphorylation in 
      granulosa cells. Based on these observations, we conclude that in granulosa 
      cells, FSH uses a protein kinase A-/ERK-dependent pathway to stimulate TSC2 
      phosphorylation and mTOR signaling, and DHT treatment significantly reduces this 
      response.
FAU - Kayampilly, Pradeep P
AU  - Kayampilly PP
AD  - Department of Obstetrics and Gynecology, University of Michigan Medical School, 
      Ann Arbor, Michigan 48109, USA.
FAU - Menon, K M J
AU  - Menon KM
LA  - eng
GR  - HD-38424/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070517
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Androgens)
RN  - 0 (Tsc2 protein, rat)
RN  - 0 (Tuberous Sclerosis Complex 2 Protein)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 08J2K08A3Y (Dihydrotestosterone)
RN  - 9002-68-0 (Follicle Stimulating Hormone)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Androgens/pharmacology
MH  - Animals
MH  - Cell Division/physiology
MH  - Cells, Cultured
MH  - Dihydrotestosterone/pharmacology
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Female
MH  - Follicle Stimulating Hormone/*metabolism
MH  - Granulosa Cells/cytology/*enzymology
MH  - MAP Kinase Signaling System/drug effects/*physiology
MH  - Phosphorylation/drug effects
MH  - Protein Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - TOR Serine-Threonine Kinases
MH  - Tuberous Sclerosis Complex 2 Protein
MH  - Tumor Suppressor Proteins/*metabolism
EDAT- 2007/05/19 09:00
MHDA- 2007/09/12 09:00
CRDT- 2007/05/19 09:00
PHST- 2007/05/19 09:00 [pubmed]
PHST- 2007/09/12 09:00 [medline]
PHST- 2007/05/19 09:00 [entrez]
AID - en.2007-0202 [pii]
AID - 10.1210/en.2007-0202 [doi]
PST - ppublish
SO  - Endocrinology. 2007 Aug;148(8):3950-7. doi: 10.1210/en.2007-0202. Epub 2007 May 
      17.