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  • Title: Differential modulation of porcine theca, granulosa, and luteal cell steroidogenesis in vitro by tumor necrosis factor.
    Author: Tekpetey FR, Engelhardt H, Armstrong DT.
    Journal: Biol Reprod; 1993 Apr; 48(4):936-43. PubMed ID: 8387351.
    Abstract:
    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)
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