The aims of these in vitro experiments were to examine the effects of short-term food restriction on ovarian secretory activity and the role of IGF-I and cAMP- and cGMP-dependent intracellular mechanisms in the control of ovarian function in domestic nutria. Slices of ovary from sexually mature animals kept under conditions of normal and restricted ((1/2) of standard ration) feeding were cultured with or without IGF-I (50 ng/ml), cAMP analogues (dbcAMP and Rp-cAMPS), and cGMP analogues (8-pCPT-cGMP and Rp-8-Br-PET-cGMPS; all at 100 nM). In nonovarian cells dbcAMP activates and Rp-cAMPS inhibits protein kinase A, while 8-p-CPT-cGMP activates and RP-8-Br-PET-cGMPS inhibits protein kinase G and cGMP-gated ion channels. IGF-I release and catabolism, as well as the release of progesterone (P), estradiol (E), and cAMP by the cultures, were evaluated using RIA. IGF-I did not affect cAMP release, while each of the cAMP and cGMP analogues inhibited IGF-I release in both control and experimental groups. Fasting did not affect cAMP or IGF-I release. It partially prevented the effect of Rp-cAMPS, but not of other cyclic nucleotides, on IGF-I release and inhibited IGF-I catabolism. The Rp-cAMPS and Rp-8-Br-PET-cGMPS also inhibited IGF-I catabolism and the effects were greater with tissue from food-restricted than control animals. Ovaries from the underfed nutria secreted significantly more P and less E than those from normally fed animals. IGF-I and both cAMP analogues, given alone, did not affect P release whereas a combination of IGF-I and Rp-cAMPS increased P output in control, but not in the experimental group. The 8-pCPT-cGMP had no effect P release. Rp-8-Br-PET-cGMPS, given alone or in combination with IGF-I, dramatically increased P secretion by tissue from control but not underfed animals. Estradiol secretion by tissue from underfed animals was stimulated by IGF-I, dbcAMP, Rp-cAMPS, 8-pCPT-cGMP, and Rp-8-Br-PET-cGMPS as well as by combinations of IGF-I and Rp-cAMPS or Rp-8-Br-PET-cGMPS; these effects were not seen with control tissue. The results demonstrate that: (1) ovaries of domestic nutria secrete IGF-I, P, E, and cAMP; (2) cAMP and cGMP can influence IGF-I release and catabolism; (3) the cyclic nucleotides may have an IGF-I-mediated effect on P and E output; (4) IGF-I and cyclic nucleotides can prevent the effect of undernutrition on E, but not on P release; (5) effects of cAMP and cGMP on P and E are probably not mediated by protein kinase A, protein kinase G, or cGMP-gated ion channels; and (6) food restriction can influence ovarian IGF-I catabolism, P, and E release and modulate the effects of cyclic nucleotides and IGF-I on steroidogenesis. It is concluded that ovarian secretory activity may be regulated separately by nutrition and the cyclic nucleotide-IGF-I system, and there may be functional interrelationships between these mechanisms.
Copyright 2000 Academic Press.