Differential modulation of porcine theca, granulosa, and luteal cell steroidogenesis in vitro by tumor necrosis factor.
The role of tumor necrosis factor alpha (TNF alpha) in ovarian function was investigated using in vitro culture of theca and granulosa cells isolated from gilt follicles (4-6 mm) and small (SLC) and large (LLC) luteal cells from mid-cycle corpora lutea. TNF alpha did not affect basal accumulation of progesterone (P) by theca cells after 72 h of culture. However, TNF alpha (0.1-100 ng/ml) caused a marked dose-dependent noncytotoxic inhibition (p < 0.05) of LH or LH+insulin (I)-stimulated P accumulation by theca cells after 72 h. Maximal inhibitions averaged 87 +/- 6% at 5 ng/ml TNF alpha for LH-stimulated P and 69 +/- 4% at 50 ng/ml TNF alpha for LH+I-stimulated P. The inhibitory effect of TNF alpha, evident by 24 h after culture, progressively increased on Days 2 and 3 of culture. The effect of TNF alpha on theca cells was mediated by cAMP generation as evidenced by TNF alpha inhibition of LH-induced cAMP accumulation and P accumulation in response to LH and forskolin but not dibutyryl cAMP. Consistent was this, TNF alpha had no effect on increased P accumulation by theca cells in the presence of 22-hydroxycholesterol or pregnenolone alone, but inhibited further increases in P accumulation stimulated by LH plus sterol substrates. Unlike that in theca cells, FSH-induced P accumulation in granulosa cell cultures was slightly enhanced (p < 0.05) by low doses of TNF alpha (0.1, 0.5, and 1.0 ng/ml) after 72 h, while higher doses (5-50 ng/ml) did not alter P accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Obstetrics, University of Western Ontario, London, Canada.
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Tekpetey
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Engelhardt
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Armstrong
D000735:Androstenedione / Q000096:biosynthesis; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008184:Luteal Cells / Q000187:drug effects / Q000378:metabolism; D010053:Ovary / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011374:Progesterone / Q000096:biosynthesis*; D013552:Swine; D013799:Theca Cells / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology* / Q000502:physiology
D014409:Tumor Necrosis Factor-alpha; D000735:Androstenedione; D011374:Progesterone; D000242:Cyclic AMP