Effects of tumour necrosis factor-alpha on growth hormone and interleukin 6 mRNA in ovine pituitary cells.
The inflammatory cytokines tumour necrosis factor-alpha (TNF alpha), interleukin 1 (IL-1) and interleukin 6 (IL-6) have been demonstrated to influence pituitary hormone synthesis directly and via the hypothalamus. Furthermore, IL-6 is produced by some anterior pituitary cells suggesting a paracrine/autocrine role for this cytokine. We show that TNF alpha induces dispersed ovine pituitary cells to produce increased levels of growth hormone (GH) and IL-6 mRNA and secreted IL-6 in a dose and time dependent manner. TNF alpha at concentrations between 1-1000 U/ml increased GH and IL-6 mRNA, relative to control levels, by 5 h post-stimulation. For IL-6, TNF alpha increased specific mRNA at 5 h and 12 h but not 24 h post-stimulation. TNF alpha also induced secreted IL-6 to levels above that spontaneously secreted at all time points from 5 h to 48 h. Levels of common glycoprotein alpha-subunit and follicle stimulating hormone-beta (FSH beta) subunit mRNA were unaffected by TNF alpha. We conclude that TNF alpha can regulate both GH and IL-6 synthesis in dispersed ovine pituitary cells. The implications for paracrine/autocrine control of pituitary hormone synthesis in acute and chronic disease are discussed.
Nash
A D
AD
Centre for Animal Biotechnology, School of Veterinary Science, University of Melbourne, Parkville, Victoria, Australia.
Brandon
M R
MR
Bello
P A
PA
D000818:Animals; D015152:Blotting, Northern; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D013006:Growth Hormone / Q000096:biosynthesis*; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000096:biosynthesis*; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis*; D012337:RNA, Ribosomal, 18S / Q000096:biosynthesis; D012756:Sheep; D013997:Time Factors; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D015850:Interleukin-6; D012333:RNA, Messenger; D012337:RNA, Ribosomal, 18S; D014409:Tumor Necrosis Factor-alpha; D013006:Growth Hormone