PMID- 16467141
OWN - NLM
STAT- MEDLINE
DCOM- 20060613
LR  - 20240412
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 103
IP  - 8
DP  - 2006 Feb 21
TI  - In search of rat stem Leydig cells: identification, isolation, and 
      lineage-specific development.
PG  - 2719-24
AB  - Leydig cells (LCs) are thought to differentiate from spindle-shaped precursor 
      cells that exhibit some aspects of differentiated function, including 
      3beta-hydroxysteroid dehydrogenase (3betaHSD) activity. The precursor cells 
      ultimately derive from undifferentiated stem LCs (SLCs), which are postulated to 
      be present in testes before the onset of precursor cell differentiation. We 
      searched for cells in the neonatal rat testis with the abilities to: (i) 
      proliferate and expand indefinitely in vitro (self renew); (ii) differentiate 
      (i.e., 3betaHSD and ultimately synthesize testosterone); and (iii) when 
      transplanted into host rat testes, colonize the interstitium and subsequently 
      differentiate in vivo. At 1 week postpartum, spindle-shaped cells were seen in 
      the testicular interstitium that differed from the precursor cells in that they 
      were 3betaHSD-negative, luteinizing hormone (LH) receptor (LHR)-negative, and 
      platelet-derived growth factor receptor alpha (PDGFR alpha)-positive. These cells 
      were purified from the testes of 1-week-old rats. The cells contained proteins 
      known to be involved in LC development, including GATA4, c-kit receptor, and 
      leukemia inhibitory factor receptor. The putative SLCs expanded over the course 
      of 6 months while remaining undifferentiated. When treated in media that 
      contained thyroid hormone, insulin-like growth factor I, and LH, 40% of the 
      putative SLCs came to express 3betaHSD and to synthesize testosterone. When 
      transplanted into host rat testes from which LCs had been eliminated, the 
      putative SLCs colonized the interstitium and subsequently expressed 3betaHSD, 
      demonstrating their ability to differentiate in vivo. We conclude that these 
      cells are likely to be the sought-after SLCs.
FAU - Ge, Ren-Shan
AU  - Ge RS
AD  - Population Council, 1230 York Avenue, New York, NY 10021, USA.
FAU - Dong, Qiang
AU  - Dong Q
FAU - Sottas, Chantal M
AU  - Sottas CM
FAU - Papadopoulos, Vassilios
AU  - Papadopoulos V
FAU - Zirkin, Barry R
AU  - Zirkin BR
FAU - Hardy, Matthew P
AU  - Hardy MP
LA  - eng
GR  - R01 HD033000/HD/NICHD NIH HHS/United States
GR  - HD-33000/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20060208
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Receptors, LH)
RN  - 0 (Thyroid Hormones)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 9002-67-9 (Luteinizing Hormone)
RN  - EC 1.1.- (3-Hydroxysteroid Dehydrogenases)
RN  - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor alpha)
SB  - IM
MH  - 3-Hydroxysteroid Dehydrogenases/analysis/*metabolism
MH  - Animals
MH  - Cell Differentiation
MH  - *Cell Lineage
MH  - Insulin-Like Growth Factor I/pharmacology
MH  - Leydig Cells/chemistry/*cytology/drug effects
MH  - Luteinizing Hormone/pharmacology
MH  - Male
MH  - Rats
MH  - Receptor, Platelet-Derived Growth Factor alpha/analysis
MH  - Receptors, LH/analysis
MH  - Stem Cell Transplantation
MH  - Stem Cells/chemistry/*cytology/drug effects
MH  - Testis/cytology
MH  - Thyroid Hormones/pharmacology
PMC - PMC1413776
COIS- Conflict of interest statement: No conflicts declared.
EDAT- 2006/02/10 09:00
MHDA- 2006/06/14 09:00
PMCR- 2006/02/21
CRDT- 2006/02/10 09:00
PHST- 2006/02/10 09:00 [pubmed]
PHST- 2006/06/14 09:00 [medline]
PHST- 2006/02/10 09:00 [entrez]
PHST- 2006/02/21 00:00 [pmc-release]
AID - 0507692103 [pii]
AID - 1134 [pii]
AID - 10.1073/pnas.0507692103 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2719-24. doi: 
      10.1073/pnas.0507692103. Epub 2006 Feb 8.