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Estrogen Receptor beta Selective Ligand 5 alpha -Androstane-3 beta , 17 beta -Diol Stimulates Spermatogonial Deoxyribonucleic Acid Synthesis in Rat Seminiferous Epithelium in Vitro

Gonadotropins and testosterone are important regulators of spermatogenesis, even though gonadotropin receptors and the androgen receptor are not expressed by germ cells. However, a functional role for estrogens in connection with male reproduction has been postulated on the basis of the phenotypes o...

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Bibliographic Details
Published in:Endocrinology (Philadelphia) 2008-06, Vol.149 (6), p.2917-2922
Main Authors: Wahlgren, Aida, Svechnikov, Konstantin, Strand, Mona-Lisa, Jahnukainen, Kirsi, Parvinen, Martti, Gustafsson, Jan-Aake, Soeder, Olle
Format: Article
Language:English
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Summary:Gonadotropins and testosterone are important regulators of spermatogenesis, even though gonadotropin receptors and the androgen receptor are not expressed by germ cells. However, a functional role for estrogens in connection with male reproduction has been postulated on the basis of the phenotypes of mice lacking estrogen receptor (ER) and cytochrome P-450 aromatase. This has further support by findings of ER expression in the testis, including that of ER beta in spermatogonia. 5 alpha -Androstane-3 beta , 17 beta -diol (3 beta Adiol), a metabolite of testosterone produced via the intermediate potent androgen 5 alpha -dihydrotestosterone (DHT), has been reported to selectively bind ER beta rather than ER alpha , but not androgen receptor. Here, we have characterized the influence of 17 beta -estradiol (E), the major physiological estrogen, 3 beta Adiol, and DHT on DNA synthesis in vitro by segments of the seminiferous epithelium at different stages of the seminiferous epithelial cycle in the rat. E and 3 beta Adiol exerted similar stimulatory effects on premitotic DNA synthesis in stage I segments, whereas other stages tested (V, VIIa, and XIII-IX) remained unresponsive. In contrast, DHT had no effect on this process. 5-bromo-2'-deoxyuridine labeling of stage I segments revealed a 30-fold higher labeling index in the presence than in the absence of E, and the labeled cells were identified as spermatogonia. Moreover, high levels of 3 beta Adiol were found in the testis of intact rats as well as in primary cultures of rat Leydig cells in response to human chorionic gonadotropin. We suggest that 3 beta Adiol may serve as a growth factor for germ cells stimulating premitotic DNA synthesis in connection with spermatogenesis via an ER beta -dependent pathway.
ISSN:0013-7227
DOI:10.1210/en.2007-1126