In the present in vitro experiments we examined FSH- and ghrelin-induced changes in ovarian hormone secretion by transgenic rabbits. Fragments of ovaries isolated from adult transgenic (carrying mammary gland-specific mWAP-hFVIII gene) and non-transgenic rabbits from the same litter were cultured with and without FSH or ghrelin (both at 0, 1, 10 or 100 ng/ml medium). The secretion of progesterone (P-4), estradiol (E-2) and insulin-like growth factor I (IGF-I) was assessed by RIA. It was observed that ovaries isolated from transgenic rabbits secreted much less P-4, E-2 and IGF-I than the ovaries of non-transgenic animals. In control animals FSH reduced E-2 (at doses 1-100 ng/ml medium) and IGF-I (at 1-100 ng/ml), but not P-4 secretion, whereas ghrelin promoted P-4 (at 1 ng/ml) and IGF-I (at 100 ng/ml), but not E-2 output. In transgenic animals, the effects were reversed: FSH had a stimulatory effect on E-2 (at 100 ng/ml) and ghrelin had an inhibitory effect on P-4 (at 10 ng/ml). No differences in the pattern of influence of FSH on P-4 and IGF-I and of ghrelin on E-2 and IGF-I were found between control and transgenic animals. The present observations suggest that 1) both FSH and ghrelin are involved in rabbit ovarian hormone secretion, 2) transgenesis in rabbits is associated with a reduction in ovarian secretory activity, and 3) transgenesis can affect the response of ovarian cells to hormonal regulators.