There is presently considerable interest in endocrine disruption which is a new area of endocrinology concerned with chemicals that mimic hormones, in particular sex steroids. It has been hypothesised that exposure to such chemicals may be responsible for adverse effects in both humans and wildlife. Until now, chemicals that mimic oestrogens (so-called xenoestrogens) have been the main focus of endocrine disruption research. However, recent evidence suggests that many abnormalities in the male reproductive system may be mediated via the androgen receptor. By blocking androgen action, exposure to an anti-androgen may cause changes similar to those associated with oestrogen exposure.We have used in vitro yeast-based assays to detect oestrogenic, anti-oestrogenic, androgenic and antiandrogenic activities in a variety of chemicals of current interest. We show that many of the so-called 'environmental oestrogens' also possess anti-androgenic activity. The previously reported anti-androgenic activities of vinclozolin and p,p -1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (DDE) were confirmed. We also found that o,p -1,1,1,-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), bisphenol A and butyl benzyl phthalate were anti-androgenic. However, not all xenoestrogens are also anti-androgenic, because nonylphenol was found to be a weak androgen agonist. Our results demonstrate that hormone-mimicking chemicals can have multiple hormonal activities, which may make it difficult to interpret their mechanisms of action in vivo.Although not a specific objective of this study, our results also demonstrate that yeast-based assays are powerful tools with which to investigate both agonist and antagonistic hormonal activities of chemicals.
Concern about possible adverse effects caused by the inadvertent exposure of humans and wildlife to endocrine active chemicals, has led some countries to develop an in vitro-in vivo screening programme for endocrine effects.In this paper, a previously described estrogen-inducible recombinant yeast strain (Saccharomyces cerevisiae), is used to investigate a number of issues that could potentially lead to the mislabelling of chemicals as endocrine disruptors. The chemicals studied were; 17 -estradiol, dihydrotestosterone, testosterone, estradiol-3-sulfate, 4-nonylphenol, 4-tertoctylphenol, 4-tert-butylphenol, bisphenol-A, methoxychlor, 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane, butyl benzyl phthalate, 4-hydroxytamoxifen, and ICI 182,780. Many of the issues raised will also affect other in vitro assays for endocrine activity, and some will be relevant to the interpretation of data from in vivo assays. These examples illustrate that considerable care and thought must be applied when interpreting results derived from any single assay. Only by using a suite of assays will we minimise the chances of wrongly labelling chemicals as endocrine disruptors.2
Two experiments, one using 0+ the other 1 + rainbow trout, were conducted to investigate the effect of prolonged starvation on plasma growth hormone levels. The results from both experiments were essentially the same. As expected, starvation resulted in cessation of growth and in a lower coefficient of condition, whereas fed fish continued to grow and remained in good condition. Starvation had relatively little effect on the plasma cortisol level; in one experiment levels were elevated temporarily in starved fish, although by the end of the experiment there was no longer any difference between starved and fed fish, and in the other experiment plasma cortisol levels remained very low throughout the course of the experiment in both starved and fed fish. In contrast, in both experiments starvation had a pronounced effect on the plasma growth hormone level, which rose steadily during both experiments, such that it was six times higher after 1 month of starvation in 0+ fish. and five times higher after 6 weeks of starvation in 1 + fish. Thus, paradoxically, fed fish had very low plasma growth hormone levels and grew rapidly, whereas starved fish had elevated plasma growth hormone levels but did not grow. In both experiments a strong negative correlation was observed between the plasma growth hormone level and the coefficient of condition of the fish. The results are discussed with regard to the well-established metabolic changes that occur during starvation, and it is suggested that a major role of growth hormone during starvation is to aid in the mobilisation of fatty acids and glycerol from adipose stores.
Various aspects of the reproductive physiology of the female lesser spotted dogfish, Scyliorhinus cuniculu L., demonstrate marked annual cycles. Pituitary ventral lobe gonadotrophin content and plasma oestradiol and testosterone levels rise through the autumn as the ovary recrudesces and the percentage of fish bearing eggs in the oviducts increases. The pituitary gonadotrophin and plasma sex steroid levels remain elevated throughout the winter but decrease during the spring, two months prior to a fall in both the gonadosomatic index (GSI) and the percentage of fish with eggs in their oviducts. The lowest gonadotrophin and sex steroid levels are found in early summer, again preceding the minimum GSI and rate of egg-laying by two or three months. Some of these cycles are pronounced, the pituitary gonadotrophin levels varying by more than 100-fold, and the oestradiol levels by more than 10-fold, throughout the year. It is concluded that the female dogfish has a very extended breeding season, though the peak frequency of egg-laying occurs in the winter and spring.
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