Barakat Badia, O'Connor Anne E, Gold Elspeth, de Kretser David M, Loveland Kate L
Monash Institute of Medical Research, Monash University, 27-31 Wright Street, Clayton, Melbourne VIC 3168, Australia.
Reproduction. 2008 Sep;136(3):345-59. doi: 10.1530/REP-08-0140. Epub 2008 May 30.
Testicular development is governed by the combined influence of hormones and proteins, including FSH, inhibins, activins and follistatin (FST). This study documents the expression of these proteins and their corresponding mRNAs, in testes and serum from mice aged 0 through 91 days post partum (dpp), using real-time PCR, in situ hybridisation, immunohistochemistry, ELISA and RIA. Serum immunoactive total inhibin and FSH levels were negatively correlated during development, with FSH levels rising and inhibin levels falling. Activin A production changed significantly during development, with subunit mRNA and protein levels declining rapidly after 4 dpp, while simultaneously levels of the activin antagonists, FST and inhibin/activin beta(C), increased. Inhibin/activin beta(A) and beta(B) subunit mRNAs were detected in Sertoli, germ and Leydig cells throughout testis development, with the beta(A) subunit also detected in peritubular myoid cells. The alpha, beta(A), beta(B) and beta(C) subunit proteins were detected in Sertoli and Leydig cells of developing and adult mouse testes. While beta(A) and beta(B) subunit proteins were observed in spermatogonia and spermatocytes in immature testes, beta(C) was localised to leptotene and zygotene spermatocytes in immature and adult testes. Nuclear beta(A) subunit protein was observed in primary spermatocytes and nuclear beta(C) subunit in gonocytes and round spermatids. The changing spatial and temporal distributions of inhibins and activins indicate that their modulated synthesis and action are important during onset of murine spermatogenesis. This study provides a foundation for evaluation of these proteins in mice with disturbed testicular development, enabling their role in normal and perturbed spermatogenesis to be more fully understood.
睾丸发育受激素和蛋白质的共同影响,包括促卵泡激素(FSH)、抑制素、激活素和卵泡抑素(FST)。本研究利用实时聚合酶链反应、原位杂交、免疫组织化学、酶联免疫吸附测定和放射免疫分析,记录了产后0至91天(dpp)小鼠睾丸和血清中这些蛋白质及其相应mRNA的表达情况。在发育过程中,血清免疫活性总抑制素和FSH水平呈负相关,FSH水平升高而抑制素水平下降。激活素A的产生在发育过程中发生显著变化,其亚基mRNA和蛋白质水平在4 dpp后迅速下降,而同时激活素拮抗剂FST和抑制素/激活素β(C)的水平升高。在整个睾丸发育过程中,在支持细胞、生殖细胞和间质细胞中均检测到抑制素/激活素β(A)和β(B)亚基mRNA,在睾丸肌样细胞中也检测到β(A)亚基。在发育中和成年小鼠睾丸的支持细胞和间质细胞中检测到α、β(A)、β(B)和β(C)亚基蛋白质。虽然在未成熟睾丸的精原细胞和精母细胞中观察到β(A)和β(B)亚基蛋白质,但β(C)定位于未成熟和成年睾丸中的细线期和偶线期精母细胞。在初级精母细胞中观察到核β(A)亚基蛋白质,在生殖细胞和圆形精子细胞中观察到核β(C)亚基。抑制素和激活素在空间和时间上分布的变化表明,它们的合成和作用的调节在小鼠精子发生开始过程中很重要。本研究为评估睾丸发育异常小鼠中的这些蛋白质提供了基础,有助于更全面地了解它们在正常和异常精子发生中的作用。