In Murray Darling rainbowfish confirming the expected in viv
In Murray–Darling rainbowfish, confirming the expected in vivo effects of androgenic progestins could be achieved using short-term exposures and determining expression profiles for androgen-responsive genes, or in longer term exposures by monitoring fecundity or the development of male secondary sex characteristics in females. Stable receptor-driven reporter cell lines such as those implemented in the present study could help to determine possible modes of action of other mmae synthesis of progestins and thus support the in vivo studies necessary to establish possible risks to fish heath posed by the presence of synthetic progestins in the aquatic environment. The cell lines described here could also be useful for the routine screening of environmental samples for androgenic and progestogenic activity with greater relevance to possible effects in fish than other assays currently used for such purposes, which rely on human-derived receptors (, , ). Because exposure to progestins and other synthetic endocrine-active compounds is most likely to occur via the release of treated wastewater, additional effluent monitoring studies would assist in determining whether synthetic progestins or their metabolites can occur in aquatic environments at levels that may represent a concern to fish populations.
Introduction Breast cancer is a highly prevalent malignancy. There are some recognized risk factors for breast cancer, like early menarche or late menopause, which increase the length of the exposure to hormones, as a result of a higher number of ovarian cycles . Moreover, there is evidence supporting the link between the use of menopausal hormone therapy (MHT) and risk for breast cancer. Those observations add to the demonstrated pivotal role of ovarian hormones in crucial stages of breast development, like puberty and pregnancy, and in experimental breast tumorigenesis. The accumulation of those evidences, together with initial findings in epidemiologic studies with combined oral contraceptive (OC) users, took the Working Group of the International Agency for Research on Cancer (IARC/WHO) to state that OC are carcinogenic to humans . That qualification has been maintained in a more recent document from the Agency . As a sort of proof of concept, some clinical trials have shown that the down-regulation of the exposure to estrogens, either by using selective estrogen receptors modulators (SERM) or by abrogating the production of estrogens with aromatase inhibitors (AI), relates with a reduction in the risk for breast cancer [, ]. While AI have been used with postmenopausal women, SERMs like tamoxifen have shown risk reduction potential for breast cancer also in premenopausal women. The above information defines a framework of very high interest for investigators, clinicians and users. It is not only that, when needed, the risk for breast cancer may be reduced thanks to the availability of drugs like SERMs or AI, but also that the accumulation of clinical data in the latter years is offering a more calibrated information of the real risk associated with hormones, either hormonal contraceptives or MHT. Therefore, the global message for premenopausal women, the population layer using hormonal contraceptives, is not of alarm but of hope, given the low impact of contraceptives on breast cancer incidence, the undetectable effect on mortality, and the long-term reduced risk on ovarian and endometrial cancer . In order to improve the understanding of the particulars involved in the action of hormones, the sections below update the mechanisms regulating hormonal action, as well as the new modulating options offered by SERMs and selective progesterone receptor modulators (SPRM).
Biological plausibility Both estrogens and progesterone have been demonstrated a main role in steps leading to the development and differentiation of cells from the main compartments in the mammary gland. Mouse models have shown that postnatal morphogenesis in the breast is triggered by both estrogens and progesterone . The action occurs in some of the epithelial cells, which already express estrogen and progesterone receptors (ER and PR).