Insulin-like growth factor (IGF)-I obliterates the pregnancy-associated protection against mammary carcinogenesis in rats: evidence that IGF-I enhances cancer progression through estrogen receptor-α activation via the mitogen-activated protein kinase pathway

INTRODUCTION: Pregnancy protects against breast cancer development in humans and rats. Parous rats have persistently reduced circulating levels of growth hormone, which may affect the activity of the growth hormone/insulin-like growth factor (IGF)-I axis. We investigated the effects of IGF-I on parity-associated protection against mammary cancer. METHODS: Three groups of rats were evaluated in the present study: IGF-I-treated parous rats; parous rats that did not receive IGF-I treatment; and age-matched virgin animals, which also did not receive IGF-I treatment. Approximately 60 days after N-methyl-N-nitrosourea injection, IGF-I treatment was discontinued and all of the animal groups were implanted with a silastic capsule containing 17β-estradiol and progesterone. The 17β-estradiol plus progesterone treatment continued for 135 days, after which the animals were killed. RESULTS: IGF-I treatment of parous rats increased mammary tumor incidence to 83%, as compared with 16% in parous rats treated with 17β-estradiol plus progesterone only. Tumor incidence and average number of tumors per animal did not differ between IGF-I-treated parous rats and age-matched virgin rats. At the time of N-methyl-N-nitrosourea exposure, DNA content was lowest but the α-lactalbumin concentration highest in the mammary glands of untreated parous rats in comparison with age-matched virgin and IGF-I-treated parous rats. The protein levels of estrogen receptor-α in the mammary gland was significantly higher in the age-matched virgin animals than in untreated parous and IGF-I-treated parous rats. Phosphorylation (activation) of the extracellular signal-regulated kinase-1/2 (ERK1/2) and expression of the progesterone receptor were both increased in IGF-I-treated parous rats, as compared with those in untreated parous and age-matched virgin rats. Expressions of cyclin D(1 )and transforming growth factor-β(3 )in the mammary gland were lower in the age-matched virgin rats than in the untreated parous and IGF-I-treated parous rats. CONCLUSION: We argue that tumor initiation (transformation and fixation of mutations) may be similar in parous and age-matched virgin animals, suggesting that the main differences in tumor formation lie in differences in tumor progression caused by the altered hormonal environment associated with parity. Furthermore, we provide evidence supporting the notion that tumor growth promotion seen in IGF-I-treated parous rats is caused by activation of estrogen receptor-α via the Raf/Ras/mitogen-activated protein kinase cascade

The poor health of deep-water species in the context of fishing

Many deep‐water fish populations, being k‐selected species, have little resilience to overexploitation and may be at serious risk of depletion as a consequence. Sea warming represents an additional threat. In this study, the condition, or health, of several populations of common ling (Molva molva), blue ling (M. dypterygia) and Mediterranean or Spanish ling (M. macrophthalma) inhabiting different areas in the North Atlantic and the Mediterranean was evaluated, in order to shed light on the challenges these deep water species are facing in the context of fishing activity and a warming climate. The data on the condition of Molva populations which we analyze here has been complemented with data on abundance and, for the southernmost species (Mediterranean ling), with two other health indicators (parasitism and hepatosomatic index). Despite some exceptions (e.g., common ling in Icelandic waters), this study shows that the condition of many populations of Molva species in the Northeastern Atlantic and the Mediterranean Sea has worsened, a trend which, in recent decades, has usually been found to be accompanied by a decline in their abundance. In addition, the poor health status of most of the populations of common ling, blue ling and Mediterranean ling considered in this analysis points to a lower sustainability of these populations in the future. Overall, the health status and abundance of Molva populations in the Northeastern Atlantic and the Mediterranean suggest that only some populations located in the north Atlantic may be able to rebuild, whereas the populations in southern North Atlantic and the Mediterranean, which are probably most at risk from sea warming, are facing serious difficulties in doing so. In the context of fisheries and global warming, our results strongly indicate that management bodies need to consider the health status of many of the populations of Molva species, particularly in southern European waters, before implementing their decisions