Reciprocal regulation of activin A and inhibin B by interleukin-1 (IL-1) and follicle-stimulating hormone (FSH) in rat Sertoli cells in vitro

• Published in: Journal of endocrinology Vol. 185; no. 1; pp. 99 - 110
• Main Authors: Okuma, Y, Saito, K, O’Connor, A E, Phillips, D J, de Kretser, D M, Hedger, M P
• Format: Journal Article
• Language: English
• Published: Colchester BioScientifica 01-04-2005; Portland Press
• Subjects: Activins - pharmacology; Animals; Biological and medical sciences; Bucladesine - pharmacology; Cell Culture Techniques; Enzyme-Linked Immunosorbent Assay - methods; Feedback, Physiological; Follicle Stimulating Hormone - pharmacology; Fundamental and applied biological sciences. Psychology; Hormone metabolism and regulation; Inhibin-beta Subunits - pharmacology; Inhibins - pharmacology; Interleukin-1 - pharmacology; Interleukin-6 - pharmacology; Male; Mammalian male genital system; Rats; Regular papers; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Sertoli Cells - drug effects; Sertoli Cells - metabolism; Stimulation, Chemical; Vertebrates: reproduction; Sertoli cell; Rat; Spermatogenesis; Cytokine; Rodentia; Gonadotropin; Testicle; Gene expression; Male genital system; In vitro; Young animal; Vertebrata; Mammalia; Adenohypophyseal hormone; Interleukin 1; Activin; Quantitative analysis; Follicle stimulating hormone
• ISSN: 0022-0795; 1479-6805
• DOI: 10.1677/joe.1.06053

In several biological systems, the inhibin βA homodimer activin A is stimulated by, and in turn, inhibits the action of interleukin (IL)-1 (both IL-1α and IL-1β) 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-1α or IL-1β, 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 βA-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 βB-subunit and, to a lesser extent, α-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.