Tumor necrosis factor-alpha stimulates proliferation of rat ovarian theca-interstitial cells.
Tumor necrosis factor-alpha (TNF-alpha) is a potent modulator of ovarian function, affecting steroidogenesis of both granulosa and theca-interstitial (T-I) cells. Women with polycystic ovary syndrome (PCOS) have increased levels of serum TNF-alpha. The present study evaluated the effects of TNF-alpha on T-I cell proliferation. Purified rat T-I cells were cultured for 48 h with or without TNF-alpha (0.001-1 nM), insulin-like growth factor I (IGF-I; 10 nM), and/or insulin (10 nM). Proliferation was measured by [(3)H]thymidine incorporation assay and by counting the steroidogenically active (stained positive for 3beta-hydroxysteroid dehydrogenase; 3beta-HSD) and inactive (3beta-HSD negative) cells. TNF-alpha stimulated thymidine incorporation in a dose-dependent fashion (up to 3.2-fold; P < 0.01). Insulin and IGF-I stimulated T-I proliferation (respectively, by up to 2.4- and 3.1-fold; P < 0.001). TNF-alpha potentiated effects of insulin and IGF-I in a dose-dependent and additive fashion (up to 6.7-fold; P < 0.001). TNF-alpha (1 nM) increased total cell count (by 80%, P < 0.05) and the proportion of 3beta-HSD-positive cells (by 19%, P < 0.05). Flow cytometry DNA analysis revealed that TNF-alpha (1 nM) increased the proliferative index by up to 16% (P = 0.05). The present findings demonstrate that TNF-alpha stimulates mitotic activity of T-I cells by increasing the proportion of actively dividing cells and preferentially increasing the number of steroidogenically active cells. The effects of TNF-alpha appear to be independent of those induced by insulin and IGF-I. We postulate that TNF-alpha may play a pathophysiologic role in disorders of the T-I compartment, such as PCOS.
Spaczynski
R Z
RZ
Karol Marcinkowski University of Medical Sciences, Department of Gynecology and Obstetrics, 60-535 Poznan, Poland.
Arici
A
A
Duleba
A J
AJ
D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000818:Animals; D002452:Cell Count; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D011085:Polycystic Ovary Syndrome / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013799:Theca Cells / Q000166:cytology / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha; D015096:3-Hydroxysteroid Dehydrogenases