Changes in Circulating and Testicular Levels of Inhibin A and B and Activin A During Postnatal Development in the Rat

Abstract

This study describes the testicular levels of inhibin/activin subunits by Northern analysis and in situ hybridization and serum and testicular levels of inhibins A and B and activin A by enzyme linked immunosorbent assays (ELISA) during postnatal development in the rat. We show that serum inhibin A levels are less than 4 pg/ml throughout postnatal life. Serum inhibin B levels peak at 572 +/- 119 pg/ml (mean +/- se) at d 40 post partum (pp) before falling to 182 +/- 35 pg/ml in mature males. Serum activin A decreases from 294 +/- 29 pg/ml at d 6 to 132 +/- 27 pg/ml at maturity. Within the testis, inhibin A levels fall from 0.330 +/- 0.108 ng/g at d 15 to less than 0.004 ng/g at maturity. Inhibin B levels peak at 43.9 +/- 4.2 ng/g at d 6 before falling to 1.6 +/- 0.13 ng/g at maturity. Testicular activin A levels fall from 18.6 +/- 2.2 ng/g at d 6 to 0.094 +/- 0.013 ng/g at maturity. Northern profiles of testicular inhibin/activin subunits correlate with immunoreactive levels demonstrated by ELISA. In situ hybridization suggests that beta(A) and beta(B) subunit expression is largely restricted to the seminiferous tubule, particularly Sertoli cells, spermatogonia, and primary spermatocytes. These data support the view that inhibin B is the major inhibin in the male rat and that levels relate to Sertoli cell number and activity. Furthermore, the demonstration of high local concentrations of activin A during the period of Sertoli cell proliferation and the onset of spermatogenesis support its proposed role because a modulator of testicular development and function.

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

“…Unfortunately, the current ELISAs do not function for murine samples and hence we report total immunoactive inhibin measurements obtained using an assay that measures both inhibin A and B, and cross-reacts significantly with products of the a subunit (Robertson et al 1988). Total testicular levels of inhibin in the mouse rise from 0 dpp to a peak at 4 dpp, with a subsequent plateau to day 16 that is followed by a subsequent decline; this parallels the pattern of changing inhibin B testis concentrations in the rat (Buzzard et al 2004). The rise and plateau reflect a period of Sertoli cell proliferation in both species that culminates in the formation of a stable, non-mitotic Sertoli cell population.…”

“…In the rat, this is also reflected in rising levels of inhibin B in serum (Sharpe et al 1999, Buzzard et al 2004), but surprisingly, in the mouse, the inhibin levels in the circulation do not rise to reflect the increased total testis inhibin content. The reason for this difference is unclear, as all other species such as sheep, sub-human primates and human show a parallel rise in serum inhibin and FSH levels associated with pubertal maturation.…”

“…Several groups, including ours, have examined the levels of inhibins, activins, FSH and FST during development of the rat testis (Au et al 1986, Sharpe et al 1999, Buzzard et al 2004 and in humans at various ages (Massa et al 1992, Anawalt et al 1996, Andersson et al 1997). The present study offers the first comprehensive expression analysis of these proteins during mouse testis development, and it provides data that highlight changes occurring at specific developmental stages of normal testis development.…”

“…Little is known about the specific role of activin B in testicular function, as mice in which the b B subunit gene has been deleted do not exhibit a testicular phenotype (Vassalli et al 1994). However, in situ hybridisation studies of adult human and rat testicular tissues revealed b B subunit expression in Sertoli cells, Leydig cells and germ cells from spermatogonia to round spermatids (Marchetti et al 2003, Buzzard et al 2004, and immunoreactive b B subunit was observed in human Leydig cells and pachytene spermatocytes and round spermatids (Marchetti et al 2003).…”

Testicular defense systems: immune privilege and innate immunity

“…27 SCs also abundantly express activin A and B. 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.…”