Inhibin, activin, follistatin and FSH serum levels and testicular production are highly modulated during the first spermatogenic wave in mice

Abstract

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 b C , increased. Inhibin/activin b A and b B subunit mRNAs were detected in Sertoli, germ and Leydig cells throughout testis development, with the b A subunit also detected in peritubular myoid cells. The a, b A , b B and b C subunit proteins were detected in Sertoli and Leydig cells of developing and adult mouse testes. While b A and b B subunit proteins were observed in spermatogonia and spermatocytes in immature testes, b C was localised to leptotene and zygotene spermatocytes in immature and adult testes. Nuclear b A subunit protein was observed in primary spermatocytes and nuclear b 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.

Analysis of activin/TGFB-signaling modulators within the normal and dysfunctional adult human testis reveals evidence of altered signaling capacity in a subset of seminomas

“…Our data illustrating a differential expression of the INHA subunit between individual seminoma specimens (6 out of 28) is consistent with a previous report documenting the presence of INHA mRNA in a subset of seminomas (three out of nine) using RNAase protection assays (van Schaik et al 1997). In the normal testis, production of the INHA subunit is confined to Sertoli and Leydig cells in species, including the human and mouse (Roberts 1997, Majdic et al 1997, Barakat et al 2008. Mice lacking the INHA subunit develop Sertoli cell tumors 3-4 weeks after birth, due to excessive activin production and signaling (Matzuk et al 1992).…”

Targeting theGdnfGene in peritubular myoid cells disrupts undifferentiated spermatogonial cell development

“…In addition, ELISAs were used to measure the GDNF protein concentration in testes of WT, Het, and cKO mice. When the GDNF ELISA results were normalized to the ELISA levels for inhibin beta-B (INHBB), an indicator of Sertoli cell numbers and function (35), the GDNF levels in cKO testes were found to be reduced by about 40% compared with WT testes (Fig. 5B).…”

Testicular defense systems: immune privilege and innate immunity

“…89 The activins have functions in SC development and initiation of spermatogenesis. 90,91 Activin A inhibits the expression of pro-inflammatory cytokines, including IL-1 and IL-6, thus suppressing the testicular inflammatory responses. 92 IL-10 is also a well-defined anti-inflammatory factor in the testis.…”