Insulin-lowering agents inhibit synthesis of testosterone in ovaries of DHEA-induced PCOS rats.
BACKGROUND
Insulin-lowering agents are reported to be useful in treating polycystic ovary syndrome (PCOS) anovulation. It has been suggested that lower insulin levels secondarily affect ovarian tissue, although the direct mechanism of action has not yet been verified. Here we investigated if these agents directly affect the ovary.


METHODS
Thirty female Wister rats were studied. Six control rats were injected subcutaneously with 0.2 ml sesame oil, while 24 rats used as PCOS models were injected subcutaneously with dehydroepiandrosterone (DHEA) and divided into four groups. Six rats were injected with only DHEA, while the remaining 18 rats received metformin, pioglitazone or troglitazone. The ovaries were immunohistochemically stained with anti- testosterone and anti-17beta-HSD antibodies, and then evaluated for morphological changes.


RESULTS
In the DHEA administration group, the number of atretic follicles significantly increased compared to that of control rats. The insulin-lowering agents did not improve the multicystic appearance. Serum testosterone concentrations significantly increased with DHEA administration, but the increase was inhibited by oral administration of insulin-lowering agents. Testosterone deposits in ovarian tissue were also reduced by feeding rats insulin-lowering agents.


CONCLUSIONS
Insulin-lowering agents affected ovarian tissue by inhibiting testosterone biosynthesis in vivo.
Misugi
Takuya
T
Department of Obstetrics and Gynecology, Osaka City University Graduate School of Medicine, Osaka, Japan. misutaku1975@excite.co.jp
Ozaki
Koji
K
El Beltagy
Khaled
K
Tokuyama
Osamu
O
Honda
Ken-ichi
K
Ishiko
Osamu
O
D015067:17-Hydroxysteroid Dehydrogenases / Q000097:blood / Q000187:drug effects; D000276:Adjuvants, Immunologic / Q000633:toxicity; D000818:Animals; D002839:Chromans / Q000627:therapeutic use; D003687:Dehydroepiandrosterone / Q000633:toxicity; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D008687:Metformin / Q000627:therapeutic use; D010053:Ovary / Q000187:drug effects*; D000077205:Pioglitazone; D011085:Polycystic Ovary Syndrome / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000096:biosynthesis* / Q000097:blood; D045162:Thiazolidinediones / Q000627:therapeutic use; D000077288:Troglitazone
D000276:Adjuvants, Immunologic; D002839:Chromans; D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D013739:Testosterone; D003687:Dehydroepiandrosterone; D008687:Metformin; D015067:17-Hydroxysteroid Dehydrogenases; D000077288:Troglitazone; D000077205:Pioglitazone