Divergent mechanisms regulate proliferation/survival and steroidogenesis of thecainterstitial cells

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Abstract
Luteinizing hormone (LH) and insulin-like growth factor I (IGF-I) are recognized as major regulators of ovarian theca–interstitial (T-I) function. This study was designed to compare the effects of LH and IGF-I on T-I proliferation and steroidogenesis. Purified rat T-I cells were cultured in chemically-defined media. DNA synthesis was evaluated by a radiolabelled thymidine incorporation assay. The cells were also directly counted. Progesterone production was assessed using a specific radioimmunoassay. DNA synthesis of T-I cells was stimulated by IGF-I (10 nM) but modestly inhibited by LH (100 ng/ml). The inhibitory effect of LH was mimicked by 8Br-cAMP (10–4 to 10–3 M); forskolin (10–5 M), cholera toxin (10 ng/ml) and 3-isobutyl-methyl-xanthine (10–5 M). Stimulation of protein kinase C with phorbol 12-myristate 13-acetate (10–7 M) had no significant effect on DNA synthesis. Furthermore, DNA synthesis was not affected by testosterone (10–10 to 10–9M) or progesterone (10–9 to 10–8 M). Accumulation of progesterone was co-operatively stimulated by LH and IGF-I. These results suggest that LH-induced inhibition of T-I proliferation and/or survival is mediated via the cAMP system. IGF-I may be viewed as a co-gonadotrophin with respect to steroidogenesis but not with respect to proliferation/survival. The divergence of the effects on proliferation/survival versus steroidogenesis underscores the complexity of the interactions between LH and IGF-I signalling pathways.