Evidence for the existence of a local activin follistatin negative feedback loop in the goldfish pituitary and its regulation by activin and gonadal steroids.
Activin is an important regulator of gonadotropin expression and production in the vertebrate pituitary, and its activity is fine-tuned by its binding protein follistatin. In the present study, a full-length cDNA for follistatin was cloned in the goldfish, which shows 74% amino acid sequence identity with that of mammals. Recombinant goldfish follistatin expressed in the Chinese hamster ovary cells significantly blocked activin-induced F5-5 cell differentiation. Goldfish follistatin is expressed in a wide range of tissues including the brain, pituitary, ovary, and testis. The expression of follistatin mRNA in the pituitary is regulated by both activin and gonadal steroids in vitro. Treatment with goldfish activin B for 48 h significantly up-regulated follistatin expression in cultured pituitary cells, suggesting a closed activin-follistatin feedback loop in the pituitary. In agreement with this, both human and goldfish follistatin down-regulated the expression of follistatin itself, probably due to the neutralization of endogenous activin. Examination of FSHbeta and LHbeta expression in the same samples supports the role of activin and follistatin in the differential regulation of FSH and LH as demonstrated previously. Since the expression level of activin beta(B) in the pituitary is rather stable both in vitro and in vivo, it is conceivable that follistatin may play a pivotal regulatory role in the intra-pituitary activin system. Both estradiol and testosterone up-regulated follistatin expression in vitro, suggesting a mediating role for follistatin in steroid feedback on pituitary hormones. These results provide clues to the potential physiological roles of activin-follistatin system in the regulation of gonadotropin biosynthesis in teleosts.
Cheng
Gheorghe F Y
GF
Department of Biology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
Yuen
Chi-Wai
CW
Ge
Wei
W
D028341:Activins / Q000378:metabolism / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D003001:Cloning, Molecular; D006224:Cricetinae; D003412:Cricetulus; D004958:Estradiol / Q000494:pharmacology; D025461:Feedback, Physiological; D037201:Follicle Stimulating Hormone, beta Subunit / Q000378:metabolism; D038681:Follistatin / Q000235:genetics / Q000378:metabolism*; D006054:Goldfish / Q000378:metabolism*; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D028322:Inhibin-beta Subunits / Q000378:metabolism; D037101:Luteinizing Hormone, beta Subunit / Q000378:metabolism; D008969:Molecular Sequence Data; D010902:Pituitary Gland / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology; D014018:Tissue Distribution
D037201:Follicle Stimulating Hormone, beta Subunit; D038681:Follistatin; D012739:Gonadal Steroid Hormones; D037101:Luteinizing Hormone, beta Subunit; D011994:Recombinant Proteins; C103008:inhibin beta A subunit; D028341:Activins; D013739:Testosterone; D004958:Estradiol; D013006:Growth Hormone; D028322:Inhibin-beta Subunits