Reciprocal regulation of activin A and inhibin B by interleukin-1 (IL-1) and follicle-stimulating hormone (FSH) in rat Sertoli cells in vitro.
In several biological systems, the inhibin beta(A) homodimer activin A is stimulated by, and in turn, inhibits the action of interleukin (IL)-1 (both IL-1alpha and IL-1beta) and IL-6. The possibility that a similar regulatory relationship operates within the testis was investigated. Sertoli cells from immature (20-day-old) rats were cultured with human IL-1alpha or IL-1beta, human IL-6 and/or ovine FSH or dibutyryl cAMP. Activin A and the inhibin dimers, inhibin A and inhibin B, were measured by specific ELISA. Immunoreactive inhibin (ir-inhibin) was measured by RIA. Activin/inhibin subunit mRNA expression was measured by quantitative real-time PCR. Both IL-1 isoforms, but not IL-6, stimulated activin A secretion through increased synthesis of beta(A)-subunit mRNA. IL-1 also stimulated activin A secretion by testicular peritubular cells. In contrast to the effect on activin A, IL-1 suppressed inhibin beta(B)-subunit and, to a lesser extent, alpha-subunit mRNA expression, thereby reducing basal and FSH-stimulated inhibin B secretion by the Sertoli cells. Conversely, FSH inhibited basal activin A secretion and antagonised the stimulatory effects of IL-1. Dibutyryl cAMP partially inhibited the action of IL-1 on activin A secretion, but had no significant effect on basal activin A secretion. Secretion of inhibin A was low in all treatment groups. These data demonstrate that IL-1 and FSH/cAMP exert a reciprocal regulation of activin A and inhibin B synthesis and release by the Sertoli cell, and suggest a role for activin A as a potential feedback regulator of IL-1 and IL-6 activity in the testis during normal spermatogenesis and in inflammation.
Okuma
Y
Y
Monash Institute of Reproduction and Development, Monash University, Melbourne, Victoria, Australia.
Saito
K
K
O'Connor
A E
AE
Phillips
D J
DJ
de Kretser
D M
DM
Hedger
M P
MP
D028341:Activins / Q000494:pharmacology*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D018929:Cell Culture Techniques; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D025461:Feedback, Physiological; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D028322:Inhibin-beta Subunits / Q000494:pharmacology*; D007265:Inhibins / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012708:Sertoli Cells / Q000187:drug effects / Q000378:metabolism*; D013268:Stimulation, Chemical
D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; C422405:activin A; C422364:inhibin B; D028341:Activins; D007265:Inhibins; D003994:Bucladesine; D005640:Follicle Stimulating Hormone; D028322:Inhibin-beta Subunits