Taketo T, Thau R B, Adeyemo O, Koide S S
Biol Reprod. 1984 Feb;30(1):189-98. doi: 10.1095/biolreprod30.1.189.
Gonadal primordia, isolated from fetal mice on the 11th or 12th day of gestation, differentiated in vitro into morphologically distinct testes or ovaries after 7 days in culture. The addition of cAMP analogues into culture media prevented the differentiation of testis cords. Histological examination indicated that the basement membranes of testis cords disintegrated after treatment with cAMP analogues, while development of germ cells and Leydig cells appeared to be unaffected. Fetal testes in culture secreted testosterone which increased following addition of dibutyryl-cAMP (Bt2 c-AMP). Primordial germ cells reached prespermatogonial stage in the presence or absence of Bt2 cAMP, suggesting that progressive differentiation of primordial germ cells is independent of testis cord organization. The Bt2 cAMP-treated explants resumed testicular development after transplantation into a site beneath the kidney capsules of adult mice, although the inhibitory effect appeared irreversible in vitro. The testicular organization-preventing effect of cAMP analogues was mimicked by prostaglandins or forskolin, which are known to stimulate adenylate cyclase. The inhibitory effect of either cAMP analogues or prostaglandins was potentiated when added in combination with phosphodiesterase inhibitors. The present results suggest that increase of intracellular cAMP prevents the development of basement membrane and the assembly of cells to form testicular structures.
从妊娠第11天或12天的胎鼠分离出的性腺原基，在培养7天后，在体外分化为形态上不同的睾丸或卵巢。向培养基中添加环磷酸腺苷（cAMP）类似物可阻止睾丸索的分化。组织学检查表明，用cAMP类似物处理后，睾丸索的基底膜解体，而生殖细胞和睾丸间质细胞的发育似乎未受影响。培养中的胎儿睾丸分泌睾酮，添加二丁酰环磷腺苷（Bt2 c-AMP）后睾酮分泌增加。无论有无Bt2 cAMP，原始生殖细胞都能达到前精原细胞阶段，这表明原始生殖细胞的逐步分化独立于睾丸索的组织。将经Bt2 cAMP处理的外植体移植到成年小鼠肾被膜下的部位后，睾丸发育得以恢复，尽管这种抑制作用在体外似乎是不可逆的。已知能刺激腺苷酸环化酶的前列腺素或福斯高林可模拟cAMP类似物对睾丸组织的阻止作用。当与磷酸二酯酶抑制剂联合添加时，cAMP类似物或前列腺素的抑制作用会增强。目前的结果表明，细胞内cAMP的增加会阻止基底膜的发育以及细胞组装形成睾丸结构。
