Follistatin concentrations in male sheep increase following sham castration/castration or injection of interleukin-1β

Abstract

Plasma follistatin (FS) concentrations were determined after castration (n = 5) or sham castration (n = 4) of mature rams. Both treatments resulted in a prolonged increase in FS between 7 and 19 h after surgery, which returned to pretreatment concentrations by 24 h. Tumour necrosis factor-alpha (TNF-alpha), a sensitive maker of an acute-phase response, was undetectable in plasma, indicating that the FS response was not induced by trauma due to surgery. In a second experiment, injection of castrated rams (n = 4) with ovine recombinant interleukin-1 beta, an acute-phase mediator, resulted in a sustained rise in FS concentrations within 4 h of injection. Plasma TNF-alpha concentrations increased transiently within 1 h of interleukin-1 beta injection, indicating that an acute-phase response had been initiated. Plasma follicle-stimulating hormone (FSH) concentrations were significantly decreased at 8 and 24 h after interleukin-1 beta injection, strongly suggestive of an inhibitory effect of increased FS concentrations on the secretion of FSH. Injection of castrated rams (n = 2) with a control preparation of recombinant interleukin-2 did not induce an acute-phase response, and plasma FS and FSH concentrations were unaffected. These data show that the testis is not a major source of circulating FS, that the increase in circulating FS following sham castration/castration is not due to an acute-phase response, but that conversely FS concentrations are modulated by the acute-phase mediator, interleukin-1 beta.

Serum concentrations of activin and follistatin are elevated and run in parallel in patients with septicemia

“…Overall, activin and FS concentrations were correlated with each other ðr 2 ¼ 0:64Þ: There was no apparent relationship between activin and FS serum concentrations and the number of leukocytes ðr 2 ¼ 0:09Þ: The parallel profiles of FS, activin, and CRP suggest a causal relationship between bacterial infection and elevated activin and FS serum levels. The observed increases in FS and activin serum concentrations during the inflammatory response are in accordance with observations in animal experiments, where interleukin-1b or lipopolysaccharide (LPS) injections caused significantly elevated FS and activin serum levels (23,37,38). The onset of septicemia is often unnoticed, whereas in most cases blood sampling commenced with obvious signs of the disease; this made it impossible to determine whether the serum concentration of activin, FS or CRP was the first to rise at the beginning of the infection.…”

Acute regulation of activin A and its binding protein, follistatin, in serum and tissues following lipopolysaccharide treatment of adult male mice

“…It has already been established that follistatin is stimulated by LPS and inflammatory cytokines, including TNF-␣, IL-1␤, and activin A itself, over a much longer time frame than is activin A (13,15,29,40). Accordingly, a significant increase in follistatin mRNA in the liver was first observed at ϳ5 h in the present study, at the same time as serum follistatin levels increased.…”

“…In fact, the rapid increase in activin A in the circulation coincides with, and may even precede, the release of TNF-␣, which is one of the most rapidly released inflammatory regulators (12). Follistatin increases in the circulation several hours later, possibly in response to stimulation by activin A itself (13), although it may also be directly regulated by LPS, TNF-␣, or IL-1␤ (15,21,29).…”

Vaccination against follistatin and the effect on ovulation rate in estrus-induced gilts

“…RU28362, a synthetic glucocorticoid, decreases follistatin production in porcine endothelial cells (Michel et al 1996). Surgery has been shown to stimulate follistatin synthesis in sheep (Klein et al 1993;Phillips et al 1996). These experiments illustrate the dynamic regulation of a non-gonadal source of follistatin in response to stress, although the exact mechanism leading to changes in circulating follistatin concentrations is not clear.…”