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小鼠精囊的出生后生长依赖于5α-二氢睾酮。

Postnatal growth of mouse seminal vesicle is dependent on 5 alpha-dihydrotestosterone.

作者信息

Shima H, Tsuji M, Young P, Cunha G R

机构信息

Department of Anatomy, University of California, San Francisco 94143.

出版信息

Endocrinology. 1990 Dec;127(6):3222-33. doi: 10.1210/endo-127-6-3222.

Abstract

The seminal vesicles (SV) develop from the lower portion of the Wolffian ducts (WD) in response to androgens, which prevent their degeneration and subsequently stimulate organogenesis of the epididymis, vas deferens, seminal vesicles, and ejaculatory ducts. Earlier studies suggest that testosterone (T) is the active androgen for WD development. By contrast, development of urogenital sinus and external genitalia is dependent upon 5 alpha-dihydrotestosterone (DHT), produced by 5 alpha-reductase within the target tissue itself. To reevaluate the possible role of DHT during SV morphogenesis, SVs from 0-day-old (day of birth) mice were grown for 3, 6, or 9 days in either serum-free or serum-containing medium in the presence or absence of T (10(-7) M) or DHT (10(-8) M). The serum-free medium consisted of Ham's F-12-Dulbecco's Modified Eagle's Medium (1:1) containing insulin, transferrin, cholera toxin, BSA, and epidermal growth factor. The serum-containing medium was Ham's F-12-Dulbecco's Modified Eagle's Medium containing 10% fetal calf serum. Epithelial branching morphogenesis of SVs occurred in serum-free or serum-containing medium supplemented with either T or DHT and was comparable to that of SVs of similar ages in vivo. In serum-containing medium the DNA content of the cultures was about 2-fold higher in T-containing vs. T-deficient medium. However, in serum-free medium the DNA content was the same in cultures grown with or without T. SVs cultured under serum-free conditions in the presence of T plus 390 MSD (17 beta-N,N-diisopropylcarbamoyl-4-aza-5 alpha-androstan-3-one, an inhibitor of 5 alpha-reductase) were completely inhibited in their development, while in the presence of DHT plus 390 MSD, branching morphogenesis was comparable to that in SVs cultured in the presence of T or DHT alone. In medium lacking either T or DHT, SV development was inhibited. In addition, it was confirmed by TLC that [1 beta,2 beta-3H]T was converted into [3H]DHT at the ratio of 15.4% for the first 2 days and at 35.3% for the subsequent 2 days of the culture of SVs in serum-free medium. These data demonstrate that T is important as a precursor of DHT and DHT is the major androgen in the postnatal development of mouse SVs from the lower WD.

摘要

精囊(SV)由中肾管(WD)的下部在雄激素的作用下发育而成,雄激素可防止其退化,并随后刺激附睾、输精管、精囊和射精管的器官发生。早期研究表明,睾酮(T)是WD发育的活性雄激素。相比之下,泌尿生殖窦和外生殖器的发育依赖于靶组织自身产生的5α-二氢睾酮(DHT),由5α-还原酶产生。为了重新评估DHT在SV形态发生过程中的可能作用,将出生0天(出生日)小鼠的精囊在无血清或含血清培养基中,在有或无T(10⁻⁷M)或DHT(10⁻⁸M)的情况下培养3、6或9天。无血清培养基由含有胰岛素、转铁蛋白、霍乱毒素、牛血清白蛋白和表皮生长因子的Ham's F-12-杜尔贝科改良伊格尔培养基(1:1)组成。含血清培养基是含有10%胎牛血清的Ham's F-12-杜尔贝科改良伊格尔培养基。在补充有T或DHT的无血清或含血清培养基中,SV发生上皮分支形态发生,且与体内相似年龄的SV相当。在含血清培养基中,含T培养基中培养物的DNA含量比缺乏T的培养基高约2倍。然而,在无血清培养基中,无论有无T,培养物中的DNA含量相同。在无血清条件下,在T加390 MSD(17β-N,N-二异丙基氨基甲酰-4-氮杂-5α-雄甾-3-酮,一种5α-还原酶抑制剂)存在下培养的SV的发育完全受到抑制,而在DHT加390 MSD存在下,分支形态发生与单独在T或DHT存在下培养的SV相当。在缺乏T或DHT的培养基中,SV发育受到抑制。此外,通过薄层层析证实,在无血清培养基中培养SV的前2天,[1β,2β-³H]T以15.4%的比例转化为[³H]DHT,在随后的2天中以35.3%的比例转化。这些数据表明,T作为DHT的前体很重要,且DHT是出生后小鼠下WD来源的SV发育中的主要雄激素。

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