Exogenous granulocyte-macrophage colony-stimulating factor promotes follicular development in the newborn rat in vivo.
BACKGROUND
Expression and selective cellular localization of granulocyte-macrophage colony-stimulating factor (GM-CSF) and its receptor in ovarian tissue imply an autocrine/paracrine role in ovarian function. Evidence indicating a functional role for GM-CSF in ovarian follicular cell function has been provided by studies with GM-CSF knockout (GM-/-) mice, which suggest that GM-CSF influences events associated with murine follicular maturation.


METHODS
Immature female rats were treated with GM-CSF, FSH or saline for 5 or 10 days. Ovaries were collected for histologic examination and immunostaining determination of CYP17, a theca cell marker. In addition, ovarian section slides were evaluated by immunofluorescence for CD45, an ovarian leukocyte marker. To investigate the possible mechanism of GM-CSF action on follicular development, theca-interstitial cells (T-I) were separated and cultured. Cells were treated with increasing concentrations of GM-CSF, then evaluated for CYP17 mRNA and protein expression assays.


RESULTS
After 10 days of treatment with GM-CSF, the number of small preantral and large preantral follicles was significantly increased compared with the control group (P < 0.05). Similarly, treatment with FSH increased the number of small preantral and large preantral follicles (P < 0.05). CD45 expression measured by immunofluorescence was not different in the three groups, indicating that the distribution of leukocytes was unchanged. In addition, CYP17 was increased in the T-I cells both in vivo and in vitro after GM-CSF treatment.


CONCLUSIONS
The present results suggest that GM-CSF may play a significant role in follicular development.
Wang
Hongbo
H
Huntington Reproductive Center, Westlake Village, CA 91361, USA. whbdf@yahoo.com
Wen
Yan
Y
Polan
Mary Lake
ML
Boostanfar
Robert
R
Feinman
Michael
M
Behr
Barry
B
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008856:Microscopy, Fluorescence; D006080:Ovarian Follicle / Q000187:drug effects / Q000254:growth & development*; D010053:Ovary / Q000187:drug effects / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism; D013799:Theca Cells / Q000378:metabolism; D013997:Time Factors
D012333:RNA, Messenger; D012313:RNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D005640:Follicle Stimulating Hormone; D013254:Steroid 17-alpha-Hydroxylase; D017493:Leukocyte Common Antigens