Andersson A M, Müller J, Skakkebaek N E
Department of Growth and Reproduction, University of Copenhagen, Denmark.
J Clin Endocrinol Metab. 1998 Dec;83(12):4451-8. doi: 10.1210/jcem.83.12.5360.
To elucidate the role of germ cells in the regulation of inhibin B secretion, serum inhibin B levels in prepubertal boys and adult men whom had a concurrent testicular biopsy showing either normal or impaired testicular function were compared. In addition, by immunohistochemistry the cellular localization of the two subunits of inhibin B (alpha and betaB) were examined in adult testicular tissue with normal spermatogenesis, spermatogenic arrest, or Sertoli cell only tubules (SCO) as well as in normal testicular tissue from an infant and a prepubertal boy. Adult men with testicular biopsy showing normal spermatogenesis (n=8) or spermatogenic arrest (n=5) had median inhibin B levels of 148 pg/mL (range, 37-463 pg/mL) and 68 pg/mL (range, 29-186 pg/mL), respectively, corresponding to normal or near-normal levels of our reference population (165 and 31-443 pg/mL; n=358). Men with SCO (n=9) had undetectable or barely detectable (n=1) serum levels of inhibin B. In contrast to adults, prepubertal boys with SCO (n=12) all had measurable serum inhibin B levels that corresponded to our previously determined normal range in healthy prepubertal boys (n=114). However, in postpubertal samples from the same SCO boys, inhibin B levels were undetectable as in the adult SCO men. Intense inhibin alpha-subunit immunostaining was evident in Sertoli cells in both prepubertal and adult testes. In the prepubertal testis, positive immunostaining for the betaB-subunit was observed in Sertoli cells. In the adult testis, intense immunostaining for the betaB-subunit was evident in germ cells from the pachytene spermatocyte to early spermatid stages and to a lesser degree in Leydig cells, but not in Sertoli cells or other stages of germ cells. Thus, surprisingly, in adult men the two subunits constituting inhibin B were expressed by different cell types. We speculate that during puberty Sertoli cell maturation induces a change in inhibin subunit expression. Thus, immature Sertoli cells express both alpha and betaB inhibin subunits, whereas fully differentiated Sertoli cells only express the alpha-subunit. The correlation in adult men between serum inhibin B levels and spermatogenesis may be due to the fact that inhibin B in adult men is possibly a joint product of Sertoli cells and germ cells, including the stages from pachytene spermatocytes to early spermatids.
为阐明生殖细胞在抑制素B分泌调节中的作用,我们比较了青春期前男孩和成年男性的血清抑制素B水平,这些男性同时进行了睾丸活检,结果显示睾丸功能正常或受损。此外,通过免疫组织化学方法,我们检测了抑制素B的两个亚基(α和βB)在成年睾丸组织中的细胞定位,这些睾丸组织具有正常精子发生、生精停滞或仅支持细胞的小管(SCO),同时也检测了来自婴儿和青春期前男孩的正常睾丸组织。睾丸活检显示精子发生正常的成年男性(n = 8)和生精停滞的成年男性(n = 5)的抑制素B中位数水平分别为148 pg/mL(范围为37 - 463 pg/mL)和68 pg/mL(范围为29 - 186 pg/mL),与我们参考人群的正常或接近正常水平(165和31 - 443 pg/mL;n = 358)相对应。患有SCO的男性(n = 9)的血清抑制素B水平检测不到或几乎检测不到(n = 1)。与成年人不同,患有SCO的青春期前男孩(n = 12)的血清抑制素B水平均可测量,且与我们之前确定的健康青春期前男孩的正常范围(n = 114)相对应。然而,在来自相同SCO男孩的青春期后样本中,抑制素B水平与成年SCO男性一样检测不到。在青春期前和成年睾丸的支持细胞中均可见强烈的抑制素α亚基免疫染色。在青春期前睾丸中,在支持细胞中观察到βB亚基的阳性免疫染色。在成年睾丸中,从粗线期精母细胞到早期精子细胞阶段的生殖细胞中可见强烈的βB亚基免疫染色,在睾丸间质细胞中程度较轻,但在支持细胞或其他生殖细胞阶段未见。因此,令人惊讶的是,在成年男性中,构成抑制素B的两个亚基由不同的细胞类型表达。我们推测,在青春期期间,支持细胞的成熟会导致抑制素亚基表达的变化。因此,未成熟的支持细胞同时表达α和βB抑制素亚基,而完全分化的支持细胞仅表达α亚基。成年男性血清抑制素B水平与生精之间的相关性可能是由于成年男性中的抑制素B可能是支持细胞和生殖细胞(包括从粗线期精母细胞到早期精子细胞阶段)的联合产物。