Browsing by Subject "Androgene"

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Geschlechtsspezifische Unterschiede in der Fötalentwicklung beim Schwein
(2007) Häußler, Susanne; Claus, Rolf
Basic mechanisms of sexual differentiation in higher mammals are well established. The development of the testes is controlled by genetic mechanisms and initiated by the Y-chromosome. Further differentiation of the ?Anlagen? is performed by the presence of testicular androgens but requires no specific signal in females (basic femaleness). Speculation exists during the fetal development of pigs, because androgens are also measurable in female fetuses. In addition, the male gonad is able to synthesize remarkably high levels of estrogens. The aim of the present study was to follow up concentrations of steroids in peripheral plasma throughout fetal development, starting with week 6, and in particular to analyze changes in testicular cell populations (spermatogonia, Leydig cells) and to correlate them with testicular androgens, estrogens, 19-nortestosterone and cortisol. The expression of steroid converting enzymes such as 11beta-HSD 2 and aromatase as well as receptors were determined by immunocytochemistry and quantitative PCR. Altogether each of the stages of gestation (weeks 6, 10, 13, and 15 of pregnancy) was represented by 4 sows, so that a total of 158 fetuses were collected. Testicular steroid synthesis (testosterone, estradiol) could be demonstrated as early as week 6, but was independant of gonadotropine. 19-nortestosterone, which is formed during estrogen synthesis, was detected in amniotic fluid using a new established enzymeimmunoassay in this study. Aromatase activity clearly correlated with a wave-like pattern of cell development. Therefore the activity was elevated both during an alternating rise of Leydig cells or spermatogonia mitosis. During the rise of spermatogonia development Leydig cells remained quiescent and during the Leydig cell mitosis spermatogonia remained inactive. An increased aromatase activity was observed both during the rise of spermatogonia and Leydig cell mitosis, and in consequence an elevated concentration of estradiol was found. But during an increased Leydig cell formation aromatase expression and thus estradiol synthesis was taken over by spermatogonia. It is therefore reasonable to resume that estrogens are important mitogenic signals as it was also found earlier in mature boars. The expression of glucocorticoid receptors by spermatogonia could be demonstrated for the first time in fetal pig testes. As also shown for other tissues, its likely role in testes is the differentiation of new cells. This important role also explains the expression of the enzyme 11beta-HSD 2 both by Leydig cells and spermatogonia. This enzyme is a well known fine-tuning mechanism which indicates cortisol and thus the ligand for the glucocorticoid receptor. Its expression in parallel to the rise of estrogens suggests a dependancy on estrogens. Investigating this was, however, not the topic of the present study. The demonstration of androgens both in blood plasma and amniotic fluid in female fetuses seems to contradict the principle of basic femaleness. It was shown however, that concentrations of testosterone in males increase up to 2.01 ng/ml plasma during the main period of sexual differentiation whereas female levels remain at 0.2 ng/ml so that it is simply the concentration which decides where the male differentiation does occur. It can not be ruled out, however, that low concentrations in female fetuses may have an effect on follicular differentiation, as was also demonstrated in mature sows. At the same time androgens could have a mitotic effect caused by insulin-like growth factors (IGF I + II). Thus the present investigation was able to clarify of several new mechanisms and basic data of fetal pig development. Further confirmation of the mechanisms suspected in this study may be served by an aromatase inhibitor.